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Sample records for arm docking complex

  1. Docking-complex-independent alignment of Chlamydomonas outer dynein arms with 24-nm periodicity in vitro.

    Science.gov (United States)

    Oda, Toshiyuki; Abe, Tatsuki; Yanagisawa, Haruaki; Kikkawa, Masahide

    2016-04-15

    The docking complex is a molecular complex necessary for assembly of outer dynein arms (ODAs) on the axonemal doublet microtubules (DMTs) in cilia and flagella. The docking complex is hypothesized to be a 24-nm molecular ruler because ODAs align along the DMTs with 24-nm periodicity. In this study, we rigorously tested this hypothesis using structural and genetic methods. We found that the ODAs can bind to DMTs and porcine microtubules with 24-nm periodicities even in the absence of the docking complexin vitro Using cryo-electron tomography and structural labeling, we observed that the docking complex took an unexpectedly flexible conformation and did not lie along the length of DMTs. In the absence of docking complex, ODAs were released from the DMT at relatively low ionic strength conditions, suggesting that the docking complex strengthens the electrostatic interactions between the ODA and DMT. Based on these results, we conclude that the docking complex serves as a flexible stabilizer of the ODA rather than as a molecular ruler.

  2. Cooperative binding of the outer arm-docking complex underlies the regular arrangement of outer arm dynein in the axoneme

    Science.gov (United States)

    Owa, Mikito; Furuta, Akane; Usukura, Jiro; Arisaka, Fumio; King, Stephen M.; Witman, George B.; Kamiya, Ritsu; Wakabayashi, Ken-ichi

    2014-01-01

    Outer arm dynein (OAD) in cilia and flagella is bound to the outer doublet microtubules every 24 nm. Periodic binding of OADs at specific sites is important for efficient cilia/flagella beating; however, the molecular mechanism that specifies OAD arrangement remains elusive. Studies using the green alga Chlamydomonas reinhardtii have shown that the OAD-docking complex (ODA-DC), a heterotrimeric complex present at the OAD base, functions as the OAD docking site on the doublet. We find that the ODA–DC has an ellipsoidal shape ∼24 nm in length. In mutant axonemes that lack OAD but retain the ODA-DC, ODA-DC molecules are aligned in an end-to-end manner along the outer doublets. When flagella of a mutant lacking ODA-DCs are supplied with ODA-DCs upon gamete fusion, ODA-DC molecules first bind to the mutant axonemes in the proximal region, and the occupied region gradually extends toward the tip, followed by binding of OADs. This and other results indicate that a cooperative association of the ODA-DC underlies its function as the OAD-docking site and is the determinant of the 24-nm periodicity. PMID:24979786

  3. Protein-Protein Interactions between Intermediate Chains and the Docking Complex of Chlamydomonas Flagellar Outer Arm Dynein

    Science.gov (United States)

    Ide, Takahiro; Owa, Mikito; King, Stephen M.; Kamiya, Ritsu; Wakabayashi, Ken-ichi

    2013-01-01

    Outer arm dynein (OAD) is bound to specific loci on outer-doublet-microtubules by interactions at two sites: via intermediate chain 1 (IC1) and the outer dynein arm docking complex (ODA-DC). Studies using Chlamydomonas mutants have suggested that the individual sites have rather weak affinities for microtubules, and therefore strong OAD attachment to microtubules is achieved by their cooperation. To test this idea, we examined interactions between IC1, IC2 (another intermediate chain) and ODA-DC using recombinant proteins. Recombinant IC1 and IC2 were found to form a 1:1 complex, and this complex associated with ODA-DC in vitro. Binding of IC1 to mutant axonemes revealed that there are specific binding sites for IC1. From these data, we propose a novel model of OAD-outer doublet association. PMID:23747306

  4. Transport and arrangement of the outer-dynein-arm docking complex in the flagella of Chlamydomonas mutants that lack outer dynein arms.

    Science.gov (United States)

    Wakabayashi, K; Takada, S; Witman, G B; Kamiya, R

    2001-04-01

    The outer dynein arms of Chlamydomonas flagella are attached to a precise site on the outer doublet microtubules and repeat at a regular interval of 24 nm. This binding is mediated by the outer dynein arm docking complex (ODA-DC), which is composed of three protein subunits. In this study, antibodies against the 83- and 62-kD subunits (DC83 and DC62) of the ODA-DC were used to analyze its state of association with outer arm components within the cytoplasm, and its localization in the axonemes of oda mutants. Immunoprecipitation indicates that DC83 and DC62 are preassembled within the cytoplasm, but that they are not associated with outer arm dynein. Both proteins are lost or greatly diminished in oda1 and oda3, mutants in the structural genes of DC62 and DC83, respectively, demonstrating that their association is necessary for their stable presence in the cytoplasm. Immunoelectron microscopy indicates that DC83 repeats at 24-nm intervals along the length of the doublet microtubules of oda6, which lacks outer arms; thus, outer arm periodicity may be determined by the ODA-DC. Flagellar regeneration and temporary dikaryon experiments indicate that the ODA-DC can be rapidly transported into the flagellum and assembled on the doublet microtubules independently of the outer arms and independently of flagellar growth. Unexpectedly, the intensity of ODA-DC labeling decreased toward the distal ends of axonemes of oda6 but not wild-type cells, suggesting that the outer arms reciprocally contribute to the assembly/stability of the ODA-DC.

  5. CCDC151 Mutations Cause Primary Ciliary Dyskinesia by Disruption of the Outer Dynein Arm Docking Complex Formation

    NARCIS (Netherlands)

    Hjeij, R.; Onoufriadis, A.; Watson, C.M.; Slagle, C.E.; Klena, N.T.; Dougherty, G.W.; Kurkowiak, M.; Loges, N.T.; Diggle, C.P.; Morante, N.F.; Gabriel, G.C.; Lemke, K.L.; Li, Y.; Pennekamp, P.; Menchen, T.; Konert, F.; Marthin, J.K.; Mans, D.A.; Letteboer, S.J.F.; Werner, C.; Burgoyne, T.; Westermann, C.; Rutman, A.; Carr, I.M.; O'Callaghan, C.; Moya, E.; Chung, E.M.; Consortium, U.K.; Sheridan, E.; Nielsen, K.G.; Roepman, R.; Bartscherer, K.; Burdine, R.D.; Lo, C.W.; Omran, H.; Mitchison, H.M.

    2014-01-01

    A diverse family of cytoskeletal dynein motors powers various cellular transport systems, including axonemal dyneins generating the force for ciliary and flagellar beating essential to movement of extracellular fluids and of cells through fluid. Multisubunit outer dynein arm (ODA) motor complexes, p

  6. CCDC151 mutations cause primary ciliary dyskinesia by disruption of the outer dynein arm docking complex formation

    DEFF Research Database (Denmark)

    Hjeij, Rim; Onoufriadis, Alexandros; Watson, Christopher M

    2014-01-01

    A diverse family of cytoskeletal dynein motors powers various cellular transport systems, including axonemal dyneins generating the force for ciliary and flagellar beating essential to movement of extracellular fluids and of cells through fluid. Multisubunit outer dynein arm (ODA) motor complexes...

  7. Synthesis, characterization, biological evaluation and docking studies of macrocyclic binuclear manganese(II) complexes containing 3,5-dinitrobenzoyl pendant arms.

    Science.gov (United States)

    Arthi, P; Shobana, S; Srinivasan, P; Mitu, L; Kalilur Rahiman, A

    2015-05-15

    A series of bis(phenoxo) bridged binuclear manganese(II) complexes of the type [Mn2L(1-3)](ClO4)2 (1-3) containing 3,5-dinitrobenzoyl pendant-arms have been synthesized by cyclocondensation of 2,6-diformyl-4-R-phenols (where R=CH3, C(CH3)3 or Br) with 2,2'-3,5-dinitrobenzoyliminodi(ethylamine) trihydrochloride in the presence of manganese(II) perchlorate. The IR spectra of complexes indicate the presence of uncoordinated perchlorate anions. The UV-Vis spectra of complexes suggest the distorted octahedral geometry around manganese(II) nuclei. The EPR spectra of Mn(II) complexes show a broad signal with g value 2.03-2.04, which is characteristic for octahedral high spin Mn(2+) complex. The observed room temperature magnetic moment values of the Mn(II) complexes (5.60-5.62B.M.) are less than the normal value (5.92B.M.), indicating weak antiferromagnetic coupling interaction between the two metal ions. Electrochemical studies of the complexes show two distinct quasi-reversible one electron transfer processes in the cathodic (E(1)pc=-0.73 to -0.76V, E(2)pc=-1.30 to -1.36V), and anodic (E(1)pa=1.02-1.11V, E(2)pa=1.32-1.79V) potential regions. Antibacterial efficacy of complexes have been screened against four Gram (-ve) and two Gram (+ve) bacterial strains. The DNA interaction studies suggest that these complexes bind with CT-DNA by intercalation, giving the binding affinity in the order 1>2>3. All the complexes display significant cleavage activity against circular plasmid pBR322 DNA. Docking simulation was performed to insert complexes into the crystal structure of EGFR tyrosine kinase and B-DNA at active site to determine the probable binding mode.

  8. Synthesis, characterization, biological evaluation and docking studies of macrocyclic binuclear manganese(II) complexes containing 3,5-dinitrobenzoyl pendant arms

    Science.gov (United States)

    Arthi, P.; Shobana, S.; Srinivasan, P.; Mitu, L.; Kalilur Rahiman, A.

    2015-05-01

    A series of bis(phenoxo) bridged binuclear manganese(II) complexes of the type [Mn2L1-3](ClO4)2 (1-3) containing 3,5-dinitrobenzoyl pendant-arms have been synthesized by cyclocondensation of 2,6-diformyl-4-R-phenols (where R = sbnd CH3, sbnd C(CH3)3 or sbnd Br) with 2,2‧-3,5-dinitrobenzoyliminodi(ethylamine) trihydrochloride in the presence of manganese(II) perchlorate. The IR spectra of complexes indicate the presence of uncoordinated perchlorate anions. The UV-Vis spectra of complexes suggest the distorted octahedral geometry around manganese(II) nuclei. The EPR spectra of Mn(II) complexes show a broad signal with g value 2.03-2.04, which is characteristic for octahedral high spin Mn2+ complex. The observed room temperature magnetic moment values of the Mn(II) complexes (5.60-5.62 B.M.) are less than the normal value (5.92 B.M.), indicating weak antiferromagnetic coupling interaction between the two metal ions. Electrochemical studies of the complexes show two distinct quasi-reversible one electron transfer processes in the cathodic (E1pc = -0.73 to -0.76 V, E2pc = -1.30 to -1.36 V), and anodic (E1pa = 1.02-1.11 V, E2pa = 1.32-1.79 V) potential regions. Antibacterial efficacy of complexes have been screened against four Gram (-ve) and two Gram (+ve) bacterial strains. The DNA interaction studies suggest that these complexes bind with CT-DNA by intercalation, giving the binding affinity in the order 1 > 2 > 3. All the complexes display significant cleavage activity against circular plasmid pBR322 DNA. Docking simulation was performed to insert complexes into the crystal structure of EGFR tyrosine kinase and B-DNA at active site to determine the probable binding mode.

  9. Solvent structure improves docking prediction in lectin-carbohydrate complexes.

    Science.gov (United States)

    Gauto, Diego F; Petruk, Ariel A; Modenutti, Carlos P; Blanco, Juan I; Di Lella, Santiago; Martí, Marcelo A

    2013-02-01

    Recognition and complex formation between proteins and carbohydrates is a key issue in many important biological processes. Determination of the three-dimensional structure of such complexes is thus most relevant, but particularly challenging because of their usually low binding affinity. In silico docking methods have a long-standing tradition in predicting protein-ligand complexes, and allow a potentially fast exploration of a number of possible protein-carbohydrate complex structures. However, determining which of these predicted complexes represents the correct structure is not always straightforward. In this work, we present a modification of the scoring function provided by AutoDock4, a widely used docking software, on the basis of analysis of the solvent structure adjacent to the protein surface, as derived from molecular dynamics simulations, that allows the definition and characterization of regions with higher water occupancy than the bulk solvent, called water sites. They mimic the interaction held between the carbohydrate -OH groups and the protein. We used this information for an improved docking method in relation to its capacity to correctly predict the protein-carbohydrate complexes for a number of tested proteins, whose ligands range in size from mono- to tetrasaccharide. Our results show that the presented method significantly improves the docking predictions. The resulting solvent-structure-biased docking protocol, therefore, appears as a powerful tool for the design and optimization of development of glycomimetic drugs, while providing new insights into protein-carbohydrate interactions. Moreover, the achieved improvement also underscores the relevance of the solvent structure to the protein carbohydrate recognition process.

  10. The ciliary inner dynein arm, I1 dynein, is assembled in the cytoplasm and transported by IFT before axonemal docking.

    Science.gov (United States)

    Viswanadha, Rasagnya; Hunter, Emily L; Yamamoto, Ryosuke; Wirschell, Maureen; Alford, Lea M; Dutcher, Susan K; Sale, Winfield S

    2014-10-01

    To determine mechanisms of assembly of ciliary dyneins, we focused on the Chlamydomonas inner dynein arm, I1 dynein, also known as dynein f. I1 dynein assembles in the cytoplasm as a 20S complex similar to the 20S I1 dynein complex isolated from the axoneme. The intermediate chain subunit, IC140 (IDA7), and heavy chains (IDA1, IDA2) are required for 20S I1 dynein preassembly in the cytoplasm. Unlike I1 dynein derived from the axoneme, the cytoplasmic 20S I1 complex will not rebind I1-deficient axonemes in vitro. To test the hypothesis that I1 dynein is transported to the distal tip of the cilia for assembly in the axoneme, we performed cytoplasmic complementation in dikaryons formed between wild-type and I1 dynein mutant cells. Rescue of I1 dynein assembly in mutant cilia occurred first at the distal tip and then proceeded toward the proximal axoneme. Notably, in contrast to other combinations, I1 dynein assembly was significantly delayed in dikaryons formed between ida7 and ida3. Furthermore, rescue of I1 dynein assembly required new protein synthesis in the ida7 × ida3 dikaryons. On the basis of the additional observations, we postulate that IDA3 is required for 20S I1 dynein transport. Cytoplasmic complementation in dikaryons using the conditional kinesin-2 mutant, fla10-1 revealed that transport of I1 dynein is dependent on kinesin-2 activity. Thus, I1 dynein complex assembly depends upon IFT for transport to the ciliary distal tip prior to docking in the axoneme.

  11. Accurate refinement of docked protein complexes using evolutionary information and deep learning.

    Science.gov (United States)

    Akbal-Delibas, Bahar; Farhoodi, Roshanak; Pomplun, Marc; Haspel, Nurit

    2016-06-01

    One of the major challenges for protein docking methods is to accurately discriminate native-like structures from false positives. Docking methods are often inaccurate and the results have to be refined and re-ranked to obtain native-like complexes and remove outliers. In a previous work, we introduced AccuRefiner, a machine learning based tool for refining protein-protein complexes. Given a docked complex, the refinement tool produces a small set of refined versions of the input complex, with lower root-mean-square-deviation (RMSD) of atomic positions with respect to the native structure. The method employs a unique ranking tool that accurately predicts the RMSD of docked complexes with respect to the native structure. In this work, we use a deep learning network with a similar set of features and five layers. We show that a properly trained deep learning network can accurately predict the RMSD of a docked complex with 1.40 Å error margin on average, by approximating the complex relationship between a wide set of scoring function terms and the RMSD of a docked structure. The network was trained on 35000 unbound docking complexes generated by RosettaDock. We tested our method on 25 different putative docked complexes produced also by RosettaDock for five proteins that were not included in the training data. The results demonstrate that the high accuracy of the ranking tool enables AccuRefiner to consistently choose the refinement candidates with lower RMSD values compared to the coarsely docked input structures.

  12. Theoretical Studies on Docking Dynamics and Electronic Structure in Metalloprotein Complexes

    Science.gov (United States)

    Sugiyama, Ayumu; Nishikawa, Keigo; Yamamoto, Tetsunori; Purqon, Acep; Nishikawa, Kiyoshi; Nagao, Hidemi

    2007-12-01

    An investigating of docking structure and dynamics between metalloprotein is interested from the viewpoint of searching the function of protein. We investigate the cytochrome c551 and azurin complexes by three computational methods, quantum mechanical calculation, docking searching algorism and molecular dynamics simulation. At first we present the docking structure of the cytochrome c551-azurin complexes expected by ZDOCK searching algorism. Quantum chemical calculation is tools to estimate the charge distrubution around the active site for each protein and force field parameters. From these parameters, we reproduce the protein docking dynamics by molecular dynamics simulation. We analyze some physical properties of complex system such as binding free energy, dynamical cross correlation map, and so on. We discuss the docking stability and dynamical effect of the cytochrome c551-azurin complexes.

  13. A holistic molecular docking approach for predicting protein-protein complex structure

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    A holistic protein-protein molecular docking approach,HoDock,was established,composed of such steps as binding site prediction,initial complex structure sampling,refined complex structure sampling,structure clustering,scoring and final structure selection.This article explains the detailed steps and applications for CAPRI Target 39.The CAPRI result showed that three predicted binding site residues,A191HIS,B512ARG and B531ARG,were correct,and there were five submitted structures with a high fraction of correct receptor-ligand interface residues,indicating that this docking approach may improve prediction accuracy for protein-protein complex structures.

  14. FlexAID: Revisiting Docking on Non-Native-Complex Structures.

    Science.gov (United States)

    Gaudreault, Francis; Najmanovich, Rafael J

    2015-07-27

    Small-molecule protein docking is an essential tool in drug design and to understand molecular recognition. In the present work we introduce FlexAID, a small-molecule docking algorithm that accounts for target side-chain flexibility and utilizes a soft scoring function, i.e. one that is not highly dependent on specific geometric criteria, based on surface complementarity. The pairwise energy parameters were derived from a large dataset of true positive poses and negative decoys from the PDBbind database through an iterative process using Monte Carlo simulations. The prediction of binding poses is tested using the widely used Astex dataset as well as the HAP2 dataset, while performance in virtual screening is evaluated using a subset of the DUD dataset. We compare FlexAID to AutoDock Vina, FlexX, and rDock in an extensive number of scenarios to understand the strengths and limitations of the different programs as well as to reported results for Glide, GOLD, and DOCK6 where applicable. The most relevant among these scenarios is that of docking on flexible non-native-complex structures where as is the case in reality, the target conformation in the bound form is not known a priori. We demonstrate that FlexAID, unlike other programs, is robust against increasing structural variability. FlexAID obtains equivalent sampling success as GOLD and performs better than AutoDock Vina or FlexX in all scenarios against non-native-complex structures. FlexAID is better than rDock when there is at least one critical side-chain movement required upon ligand binding. In virtual screening, FlexAID results are lower on average than those of AutoDock Vina and rDock. The higher accuracy in flexible targets where critical movements are required, intuitive PyMOL-integrated graphical user interface and free source code as well as precompiled executables for Windows, Linux, and Mac OS make FlexAID a welcome addition to the arsenal of existing small-molecule protein docking methods.

  15. Fully Blind Docking at the Atomic Level for Protein-Peptide Complex Structure Prediction.

    Science.gov (United States)

    Yan, Chengfei; Xu, Xianjin; Zou, Xiaoqin

    2016-10-04

    Protein-peptide interactions play an important role in many cellular processes. In silico prediction of protein-peptide complex structure is highly desirable for mechanistic investigation of these processes and for therapeutic design. However, predicting all-atom structures of protein-peptide complexes without any knowledge about the peptide binding site and the bound peptide conformation remains a big challenge. Here, we present a docking-based method for predicting protein-peptide complex structures, referred to as MDockPeP, which starts with the peptide sequence and globally docks the all-atom, flexible peptide onto the protein structure. MDockPeP was tested on the peptiDB benchmarking database using both bound and unbound protein structures. The results show that MDockPeP successfully generated near-native peptide binding modes in 95.0% of the bound docking cases and in 92.2% of the unbound docking cases. The performance is significantly better than other existing docking methods. MDockPeP is computationally efficient and suitable for large-scale applications.

  16. On docking, scoring and assessing protein-DNA complexes in a rigid-body framework.

    Directory of Open Access Journals (Sweden)

    Marc Parisien

    Full Text Available We consider the identification of interacting protein-nucleic acid partners using the rigid body docking method FTdock, which is systematic and exhaustive in the exploration of docking conformations. The accuracy of rigid body docking methods is tested using known protein-DNA complexes for which the docked and undocked structures are both available. Additional tests with large decoy sets probe the efficacy of two published statistically derived scoring functions that contain a huge number of parameters. In contrast, we demonstrate that state-of-the-art machine learning techniques can enormously reduce the number of parameters required, thereby identifying the relevant docking features using a miniscule fraction of the number of parameters in the prior works. The present machine learning study considers a 300 dimensional vector (dependent on only 15 parameters, termed the Chemical Context Profile (CCP, where each dimension reflects a specific type of protein amino acid-nucleic acid base interaction. The CCP is designed to capture the chemical complementarities of the interface and is well suited for machine learning techniques. Our objective function is the Chemical Context Discrepancy (CCD, which is defined as the angle between the native system's CCP vector and the decoy's vector and which serves as a substitute for the more commonly used root mean squared deviation (RMSD. We demonstrate that the CCP provides a useful scoring function when certain dimensions are properly weighted. Finally, we explore how the amino acids on a protein's surface can help guide DNA binding, first through long-range interactions, followed by direct contacts, according to specific preferences for either the major or minor grooves of the DNA.

  17. Cytotoxic gallium complexes containing thiosemicarbazones derived from 9-anthraldehyde: Molecular docking with biomolecules

    Science.gov (United States)

    Beckford, Floyd A.; Brock, Alyssa; Gonzalez-Sarrías, Antonio; Seeram, Navindra P.

    2016-10-01

    We have synthesized a trio of gallium complexes bearing 9-anthraldehyde thiosemicarbazones. The complexes were assessed for their anticancer activity and their biophysical reactivity was also investigated. The three complexes displayed good cytotoxic profiles against two human colon cancer cell lines, HCT-116 and Caco-2. The IC50 ranged from 4.7 to 44.1 μM with the complex having an unsubstituted amino group on the thiosemicarbazone being the most active. This particular complex also showed a high therapeutic index. All three complexes bind strongly to DNA via intercalation with binding constants ranging from 7.46 × 104 M-1 to 3.25 × 105 M-1. The strength of the binding cannot be directly related to the level of anticancer activity. The complexes also bind strongly to human serum albumin with binding constants on the order of 104-105 M-1 as well. The complexes act as chemical nucleases as evidenced by their ability to cleave pBR322 plasmid DNA. The binding constants along with the cleavage results may suggest that the extent of DNA interaction is not directly correlated with anticancer activity. The results of docking studies with DNA, ribonucleotide reductase and human serum albumin, however showed that the complex with the best biological activity had the largest binding constant to DNA.

  18. Prediction of peptide binding to a major histocompatibility complex class I molecule based on docking simulation.

    Science.gov (United States)

    Ishikawa, Takeshi

    2016-10-01

    Binding between major histocompatibility complex (MHC) class I molecules and immunogenic epitopes is one of the most important processes for cell-mediated immunity. Consequently, computational prediction of amino acid sequences of MHC class I binding peptides from a given sequence may lead to important biomedical advances. In this study, an efficient structure-based method for predicting peptide binding to MHC class I molecules was developed, in which the binding free energy of the peptide was evaluated by two individual docking simulations. An original penalty function and restriction of degrees of freedom were determined by analysis of 361 published X-ray structures of the complex and were then introduced into the docking simulations. To validate the method, calculations using a 50-amino acid sequence as a prediction target were performed. In 27 calculations, the binding free energy of the known peptide was within the top 5 of 166 peptides generated from the 50-amino acid sequence. Finally, demonstrative calculations using a whole sequence of a protein as a prediction target were performed. These data clearly demonstrate high potential of this method for predicting peptide binding to MHC class I molecules.

  19. An effective approach for generating a three-Cys2His2 zinc-finger-DNA complex model by docking

    Directory of Open Access Journals (Sweden)

    Rajasekaran M

    2010-06-01

    Full Text Available Abstract Background Determination of protein-DNA complex structures with both NMR and X-ray crystallography remains challenging in many cases. High Ambiguity-Driven DOCKing (HADDOCK is an information-driven docking program that has been used to successfully model many protein-DNA complexes. However, a protein-DNA complex model whereby the protein wraps around DNA has not been reported. Defining the ambiguous interaction restraints for the classical three-Cys2His2 zinc-finger proteins that wrap around DNA is critical because of the complicated binding geometry. In this study, we generated a Zif268-DNA complex model using three different sets of ambiguous interaction restraints (AIRs to study the effect of the geometric distribution on the docking and used this approach to generate a newly reported Sp1-DNA complex model. Results The complex models we generated on the basis of two AIRs with a good geometric distribution in each domain are reasonable in terms of the number of models with wrap-around conformation, interface root mean square deviation, AIR energy and fraction native contacts. We derived the modeling approach for generating a three-Cys2His2 zinc-finger-DNA complex model according to the results of docking studies using the Zif268-DNA and other three crystal complex structures. Furthermore, the Sp1-DNA complex model was calculated with this approach, and the interactions between Sp1 and DNA are in good agreement with those previously reported. Conclusions Our docking data demonstrate that two AIRs with a reasonable geometric distribution in each of the three-Cys2His2 zinc-finger domains are sufficient to generate an accurate complex model with protein wrapping around DNA. This approach is efficient for generating a zinc-finger protein-DNA complex model for unknown complex structures in which the protein wraps around DNA. We provide a flowchart showing the detailed procedures of this approach.

  20. Comparative Molecular Docking Studies with ABCC1 and Aquaporin 9 in the Arsenite Complex Efflux

    Science.gov (United States)

    Poojan, Shiv; Dhasmana, Anupam; Jamal, Qazi Mohammad Sajid; Haneef, Mohd; Lohani, Mohtashim

    2014-01-01

    Arsenic is the most toxic metalloid present in the natural environment in both organic and inorganic arsenic forms. Inorganic arsenic is often more hazardous than the organic form. Arsenite and arsenate compounds are the major inorganic forms which are toxic causing severe human health dysfunction including cancer. Excretion of arsenic from the system is found elusive. Therefore, it is of interest to screen channel proteins with the arsenic complex in the different combination of arsenic, GSH (glutathione) and arsenic, selenium using docking methods. The mode of arsenic removal. The complex structure revealed the mode of arsenic binding efficiency with the receptor aquaporine 9 and ABCC1 channel protein. This provides insights to understand the mechanism of arsenic efflux. These inferences find application in the design, identification and development of novel nutracetucal or any other formulation useful in the balance of arsenic efflux. PMID:25258480

  1. Comparative Molecular Docking Studies with ABCC1 and Aquaporin 9 in the Arsenite Complex Efflux.

    Science.gov (United States)

    Poojan, Shiv; Dhasmana, Anupam; Jamal, Qazi Mohammad Sajid; Haneef, Mohd; Lohani, Mohtashim

    2014-01-01

    Arsenic is the most toxic metalloid present in the natural environment in both organic and inorganic arsenic forms. Inorganic arsenic is often more hazardous than the organic form. Arsenite and arsenate compounds are the major inorganic forms which are toxic causing severe human health dysfunction including cancer. Excretion of arsenic from the system is found elusive. Therefore, it is of interest to screen channel proteins with the arsenic complex in the different combination of arsenic, GSH (glutathione) and arsenic, selenium using docking methods. The mode of arsenic removal. The complex structure revealed the mode of arsenic binding efficiency with the receptor aquaporine 9 and ABCC1 channel protein. This provides insights to understand the mechanism of arsenic efflux. These inferences find application in the design, identification and development of novel nutracetucal or any other formulation useful in the balance of arsenic efflux.

  2. Kinematics of star complexes within the Sgr-Car arm

    Science.gov (United States)

    Glushkova, E. V.; Uglova, I. M.

    Kinematics of open star clusters (OCL) was studied in the region of A, B, and C star complexes isolated by Avedisova (1989, Astrofizika V.30, P.140) in Sgr-Car arm. As raw data, we involved the absolute proper motions of OCL derived by the stars from the 4-Million Star Catalog of Positions and Proper Motions compiled in Sternberg Institute. The typical accuracy of these proper motions am ounts to 0.005 arcsec/yr. The distances to the clusters were taken from the catalog by Dambis (1998, in press). On the first stage, the kinematic models were calculated for three cases: (i) expansion of the complex from its center at a constant velocity in the galactic plane; (ii) the symmetric case of the complex compression, and (iii) its rotation around the center, also in the plane of Galaxy. The curves V_l(l), V_l(r), V_r(l), and V_r(r) were calculated for the objects under study (here, V_l stands for the tangential velocity component along the galactic longitude, V_r denotes the radial velocity, l is the galactic longitude, and r is the heliocentric distance. For each level of the accuracy of the input data, we calculated the minimum velocity of expansion (compression, rotation), at which the effect could ever be noticed. Our analysis of the residual velocities of 19 OCL has shown that complex A is static. This conclusion was confirmed by the behavior of 11 cepheids belonging to this complex. The study of 24 OCL in complex B provided an evidence of the fact that the complex is apparently expanding at the velocity of about 25 km/s. The investigation of the tangential velocities of 15 cepheids from this complex confirmed this fact. For complex C, where we studied 32 OCL and the radial velocities of 13 cepheids, it was found to compress at about 15 km/s.

  3. Analysis of protein-protein docking decoys using interaction fingerprints: application to the reconstruction of CaM-ligand complexes

    Directory of Open Access Journals (Sweden)

    Uchikoga Nobuyuki

    2010-05-01

    Full Text Available Abstract Background Protein-protein docking for proteins with large conformational changes was analyzed by using interaction fingerprints, one of the scales for measuring similarities among complex structures, utilized especially for searching near-native protein-ligand or protein-protein complex structures. Here, we have proposed a combined method for analyzing protein-protein docking by taking large conformational changes into consideration. This combined method consists of ensemble soft docking with multiple protein structures, refinement of complexes, and cluster analysis using interaction fingerprints and energy profiles. Results To test for the applicability of this combined method, various CaM-ligand complexes were reconstructed from the NMR structures of unbound CaM. For the purpose of reconstruction, we used three known CaM-ligands, namely, the CaM-binding peptides of cyclic nucleotide gateway (CNG, CaM kinase kinase (CaMKK and the plasma membrane Ca2+ ATPase pump (PMCA, and thirty-one structurally diverse CaM conformations. For each ligand, 62000 CaM-ligand complexes were generated in the docking step and the relationship between their energy profiles and structural similarities to the native complex were analyzed using interaction fingerprint and RMSD. Near-native clusters were obtained in the case of CNG and CaMKK. Conclusions The interaction fingerprint method discriminated near-native structures better than the RMSD method in cluster analysis. We showed that a combined method that includes the interaction fingerprint is very useful for protein-protein docking analysis of certain cases.

  4. Synthesis, anticancer activity and molecular docking study of Schiff base complexes containing thiazole moiety

    Directory of Open Access Journals (Sweden)

    Mokhles M. Abd-Elzaher

    2016-03-01

    Full Text Available A Schiff base ligand 1 was prepared from condensation of salicyaldehyde with 2-amino-4-phenyl-5-methyl thiazole. The ligand forms complexes with CoII, NiII, CuII, and ZnII in good yield. The synthesized compounds were characterized by elemental analysis, magnetic susceptibility, molar conductance, infrared spectra, 1H and 13C NMR, mass, electronic absorption and ESR spectroscopy. The anticancer activity of the synthesized compounds was studied against different human tumor cell lines: breast cancer MCF-7, liver cancer HepG2, lung carcinoma A549 and colorectal cancer HCT116 in comparison with the activity of doxorubicin as a reference drug. The study showed that ZnII complex showed potent inhibition against human TRK in the four cell lines (HepG2, MCF7, A549, HCT116 by the ratio 80, 70, 61 and 64% respectively as compared to the inhibition in the untreated cells. Moreover, the molecular docking into TRK (PDB: 1t46 was done for the optimization of the aforementioned compounds as potential TRK inhibitors.

  5. 20(S)-Protopanaxadiol Phospholipid Complex: Process Optimization, Characterization, In Vitro Dissolution and Molecular Docking Studies.

    Science.gov (United States)

    Pu, Yiqiong; Zhang, Xitong; Zhang, Qi; Wang, Bing; Chen, Yuxi; Zang, Chuanqi; Wang, Yuqin; Dong, Tina Ting-Xia; Zhang, Tong

    2016-10-19

    20(S)-Protopanaxadiol (PPD), a bioactive compound extracted from ginseng, possesses cardioprotective, neuroprotective, anti-inflammatory, antiestrogenic, anticancer and anxiolytic effects. However, the clinical application of PPD is limited by its weak aqueous solubility. In this study, we optimized an efficient method of preparing its phospholipid complex (PPD-PLC) using a central composite design and response surface analysis. The prepared PPD-PLC was characterized by differential scanning calorimetric, powder X-ray diffraction, Fourier-transformed infrared spectroscopy and nuclear magnetic resonance analyses associated with molecular docking calculation. The equilibrium solubility of PPD-PLC in water and n-octanol increased 6.53- and 1.53-times, respectively. Afterwards, using PPD-PLC as the intermediate, the PPD-PLC-loaded dry suspension (PPD-PLC-SU) was prepared with our previous method. In vitro evaluations were conducted on PPD-PLC and PPD-PLC-SU, including dissolution behaviors and stability properties under different conditions. Results of in vitro dissolution behavior revealed the improved dissolution extents and rates of PPD-PLC and PPD-PLC-SU (p PLC-SU compared with free PPD. Therefore, phospholipid complex technology is a useful formulation strategy for BCS II drugs, as it could effectively improve their hydrophilicity and lipophilicity.

  6. Involvement of complexin 2 in docking, locking and unlocking of different SNARE complexes during sperm capacitation and induced acrosomal exocytosis.

    Directory of Open Access Journals (Sweden)

    Pei-Shiue J Tsai

    Full Text Available Acrosomal exocytosis (AE is an intracellular multipoint fusion reaction of the sperm plasma membrane (PM with the outer acrosomal membrane (OAM. This unique exocytotic event enables the penetration of the sperm through the zona pellucida of the oocyte. We previously observed a stable docking of OAM to the PM brought about by the formation of the trans-SNARE complex (syntaxin 1B, SNAP 23 and VAMP 3. By using electron microscopy, immunochemistry and immunofluorescence techniques in combination with functional studies and proteomic approaches, we here demonstrate that calcium ionophore-induced AE results in the formation of unilamellar hybrid membrane vesicles containing a mixture of components originating from the two fused membranes. These mixed vesicles (MV do not contain the earlier reported trimeric SNARE complex but instead possess a novel trimeric SNARE complex that contained syntaxin 3, SNAP 23 and VAMP 2, with an additional SNARE interacting protein, complexin 2. Our data indicate that the earlier reported raft and capacitation-dependent docking phenomenon between the PM and OAM allows a specific rearrangement of molecules between the two docked membranes and is involved in (1 recruiting SNAREs and complexin 2 in the newly formed lipid-ordered microdomains, (2 the assembly of a fusion-driving SNARE complex which executes Ca(2+-dependent AE, (3 the disassembly of the earlier reported docking SNARE complex, (4 the recruitment of secondary zona binding proteins at the zona interacting sperm surface. The possibility to study separate and dynamic interactions between SNARE proteins, complexin and Ca(2+ which are all involved in AE make sperm an ideal model for studying exocytosis.

  7. On the chains of star complexes and superclouds in spiral arms

    CERN Document Server

    Efremov, Yuri N

    2010-01-01

    The relation is studied between occurrence of a regular chain of star complexes and superclouds in a spiral arm, and other properties of the latter. A regular string of star complexes is located in the north-western arm of M31; they have about the same size 0.6 kpc with spacing of 1.1 kpc. Within the same arm segment the regular magnetic field with the wavelength of 2.3 kpc was found by Beck et al. (1989). We noted that this wavelength is twice as large as the spacing between complexes and suggested that they were formed in result of magneto-gravitational instability developed along the arm. In this NW arm, star complexes are located inside the gas-dust lane, whilst in the south-western arm of M31 the gas-dust lane is upstream of the bright and uniform stellar arm. Earlier, evidence for the age gradient has been found in the SW arm. All these are signatures of a spiral shock, which may be associated with unusually large (for M31) pitch-angle of this SW arm segment. Such a shock may prevent the formation of th...

  8. Spectroscopic, docking and molecular dynamics simulation studies on the interaction of two Schiff base complexes with human serum albumin

    Energy Technology Data Exchange (ETDEWEB)

    Fani, N. [Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Bordbar, A.K., E-mail: bordbar@chem.ui.ac.ir [Department of Chemistry, University of Isfahan, Isfahan 81746-73441 (Iran, Islamic Republic of); Ghayeb, Y. [Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of)

    2013-09-15

    This study was designed to examine the interaction of two Schiff base complexes with human serum albumin (HSA), by different kinds of spectroscopic and molecular modeling techniques. Fluorescence quenching and absorption spectra were investigated in order to estimate the binding parameters. The analysis of absorption data at different temperatures were done in order to estimate the thermodynamics parameters of interactions between Schiff base complexes and HSA. The experimental data suggested that both complexes demonstrated a significant binding affinity to HSA and the process is enthalpy driven. Molecular docking study indicated that both Schiff base complexes bind to polar and apolar residues located in the subdomain IB of HSA. Molecular dynamics (MD) simulations were also performed with the GROMACS program package to study the characters of HSA in binding states. Molecular dynamics results suggested that both Schiff base complexes can interact with HSA, without affecting the secondary structure of HSA but probably with a slight modification of its tertiary structure. All the molecular docking and molecular dynamics results kept in good consistence with experimental data. -- Highlights: • The fluorescence of HSA quenched due to reacting with Schiff base complexes. • The absorbance of Schiff base complexes in the presence of HSA changed. • Binding parameters and the pose of the molecules in the binding site were estimated. • Both complexes can interact with HSA, without affecting the secondary structure. • Simulation results predicted slight compactness of tertiary structure for HSA.

  9. Chlamydomonas axonemal dynein assembly locus ODA8 encodes a conserved flagellar protein needed for cytoplasmic maturation of outer dynein arm complexes.

    Science.gov (United States)

    Desai, Paurav B; Freshour, Judy R; Mitchell, David R

    2015-01-01

    The Chlamydomonas reinhardtii oda8 mutation blocks assembly of flagellar outer dynein arms (ODAs), and interacts genetically with ODA5 and ODA10, which encode axonemal proteins thought to aid dynein binding onto axonemal docking sites. We positionally cloned ODA8 and identified the gene product as the algal homolog of vertebrate LRRC56. Its flagellar localization depends on ODA5 and ODA10, consistent with genetic interaction studies, but phylogenomics suggests that LRRC56 homologs play a role in intraflagellar transport (IFT)-dependent assembly of outer row dynein arms, not axonemal docking. ODA8 distribution between cytoplasm and flagella is similar to that of IFT proteins and about half of flagellar ODA8 is in the soluble matrix fraction. Dynein extracted in vitro from wild type axonemes will rebind efficiently to oda8 mutant axonemes, without re-binding of ODA8, further supporting a role in dynein assembly or transport, not axonemal binding. Assays comparing preassembled ODA complexes from the cytoplasm of wild type and mutant strains show that dynein in oda8 mutant cytoplasm has not properly preassembled and cannot bind normally onto oda axonemes. We conclude that ODA8 plays an important role in formation and transport of mature dynein complexes during flagellar assembly.

  10. Prediction of homoprotein and heteroprotein complexes by protein docking and template-based modeling: A CASP-CAPRI experiment

    KAUST Repository

    Lensink, Marc F.

    2016-04-28

    We present the results for CAPRI Round 30, the first joint CASP-CAPRI experiment, which brought together experts from the protein structure prediction and protein-protein docking communities. The Round comprised 25 targets from amongst those submitted for the CASP11 prediction experiment of 2014. The targets included mostly homodimers, a few homotetramers, and two heterodimers, and comprised protein chains that could readily be modeled using templates from the Protein Data Bank. On average 24 CAPRI groups and 7 CASP groups submitted docking predictions for each target, and 12 CAPRI groups per target participated in the CAPRI scoring experiment. In total more than 9500 models were assessed against the 3D structures of the corresponding target complexes. Results show that the prediction of homodimer assemblies by homology modeling techniques and docking calculations is quite successful for targets featuring large enough subunit interfaces to represent stable associations. Targets with ambiguous or inaccurate oligomeric state assignments, often featuring crystal contact-sized interfaces, represented a confounding factor. For those, a much poorer prediction performance was achieved, while nonetheless often providing helpful clues on the correct oligomeric state of the protein. The prediction performance was very poor for genuine tetrameric targets, where the inaccuracy of the homology-built subunit models and the smaller pair-wise interfaces severely limited the ability to derive the correct assembly mode. Our analysis also shows that docking procedures tend to perform better than standard homology modeling techniques and that highly accurate models of the protein components are not always required to identify their association modes with acceptable accuracy. © 2016 Wiley Periodicals, Inc.

  11. Prediction of homoprotein and heteroprotein complexes by protein docking and template‐based modeling: A CASP‐CAPRI experiment

    Science.gov (United States)

    Velankar, Sameer; Kryshtafovych, Andriy; Huang, Shen‐You; Schneidman‐Duhovny, Dina; Sali, Andrej; Segura, Joan; Fernandez‐Fuentes, Narcis; Viswanath, Shruthi; Elber, Ron; Grudinin, Sergei; Popov, Petr; Neveu, Emilie; Lee, Hasup; Baek, Minkyung; Park, Sangwoo; Heo, Lim; Rie Lee, Gyu; Seok, Chaok; Qin, Sanbo; Zhou, Huan‐Xiang; Ritchie, David W.; Maigret, Bernard; Devignes, Marie‐Dominique; Ghoorah, Anisah; Torchala, Mieczyslaw; Chaleil, Raphaël A.G.; Bates, Paul A.; Ben‐Zeev, Efrat; Eisenstein, Miriam; Negi, Surendra S.; Weng, Zhiping; Vreven, Thom; Pierce, Brian G.; Borrman, Tyler M.; Yu, Jinchao; Ochsenbein, Françoise; Guerois, Raphaël; Vangone, Anna; Rodrigues, João P.G.L.M.; van Zundert, Gydo; Nellen, Mehdi; Xue, Li; Karaca, Ezgi; Melquiond, Adrien S.J.; Visscher, Koen; Kastritis, Panagiotis L.; Bonvin, Alexandre M.J.J.; Xu, Xianjin; Qiu, Liming; Yan, Chengfei; Li, Jilong; Ma, Zhiwei; Cheng, Jianlin; Zou, Xiaoqin; Shen, Yang; Peterson, Lenna X.; Kim, Hyung‐Rae; Roy, Amit; Han, Xusi; Esquivel‐Rodriguez, Juan; Kihara, Daisuke; Yu, Xiaofeng; Bruce, Neil J.; Fuller, Jonathan C.; Wade, Rebecca C.; Anishchenko, Ivan; Kundrotas, Petras J.; Vakser, Ilya A.; Imai, Kenichiro; Yamada, Kazunori; Oda, Toshiyuki; Nakamura, Tsukasa; Tomii, Kentaro; Pallara, Chiara; Romero‐Durana, Miguel; Jiménez‐García, Brian; Moal, Iain H.; Férnandez‐Recio, Juan; Joung, Jong Young; Kim, Jong Yun; Joo, Keehyoung; Lee, Jooyoung; Kozakov, Dima; Vajda, Sandor; Mottarella, Scott; Hall, David R.; Beglov, Dmitri; Mamonov, Artem; Xia, Bing; Bohnuud, Tanggis; Del Carpio, Carlos A.; Ichiishi, Eichiro; Marze, Nicholas; Kuroda, Daisuke; Roy Burman, Shourya S.; Gray, Jeffrey J.; Chermak, Edrisse; Cavallo, Luigi; Oliva, Romina; Tovchigrechko, Andrey

    2016-01-01

    ABSTRACT We present the results for CAPRI Round 30, the first joint CASP‐CAPRI experiment, which brought together experts from the protein structure prediction and protein–protein docking communities. The Round comprised 25 targets from amongst those submitted for the CASP11 prediction experiment of 2014. The targets included mostly homodimers, a few homotetramers, and two heterodimers, and comprised protein chains that could readily be modeled using templates from the Protein Data Bank. On average 24 CAPRI groups and 7 CASP groups submitted docking predictions for each target, and 12 CAPRI groups per target participated in the CAPRI scoring experiment. In total more than 9500 models were assessed against the 3D structures of the corresponding target complexes. Results show that the prediction of homodimer assemblies by homology modeling techniques and docking calculations is quite successful for targets featuring large enough subunit interfaces to represent stable associations. Targets with ambiguous or inaccurate oligomeric state assignments, often featuring crystal contact‐sized interfaces, represented a confounding factor. For those, a much poorer prediction performance was achieved, while nonetheless often providing helpful clues on the correct oligomeric state of the protein. The prediction performance was very poor for genuine tetrameric targets, where the inaccuracy of the homology‐built subunit models and the smaller pair‐wise interfaces severely limited the ability to derive the correct assembly mode. Our analysis also shows that docking procedures tend to perform better than standard homology modeling techniques and that highly accurate models of the protein components are not always required to identify their association modes with acceptable accuracy. Proteins 2016; 84(Suppl 1):323–348. © 2016 The Authors Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc. PMID:27122118

  12. Failure of Arm Movement Control in Stroke Patients, Characterized by Loss of Complexity.

    Science.gov (United States)

    Goh, Segun; Han, Kyungreem; Ryu, Jehkwang; Kim, Seonjin; Choi, MooYoung

    2015-01-01

    We study the mechanism of human arm-posture control by means of nonlinear dynamics and quantitative time series analysis methods. Utilizing linear and nonlinear measures in combination, we find that pathological tremors emerge in patient dynamics and serve as a main feature discriminating between normal and patient groups. The deterministic structure accompanied with loss of complexity inherent in the tremor dynamics is also revealed. To probe the underlying mechanism of the arm-posture dynamics, we further analyze the coupling patterns between joints and components, and discuss their roles in breaking of the organization structure. As a result, we elucidate the mechanisms in the arm-posture dynamics of normal subjects responding to the gravitational force and for the reduction of the dynamic degrees of freedom in the patient dynamics. This study provides an integrated framework for the origin of the loss of complexity in the dynamics of patients as well as the coupling structure in the arm-posture dynamics.

  13. A machine learning approach for ranking clusters of docked protein-protein complexes by pairwise cluster comparison.

    Science.gov (United States)

    Pfeiffenberger, Erik; Chaleil, Raphael A G; Moal, Iain H; Bates, Paul A

    2017-03-01

    Reliable identification of near-native poses of docked protein-protein complexes is still an unsolved problem. The intrinsic heterogeneity of protein-protein interactions is challenging for traditional biophysical or knowledge based potentials and the identification of many false positive binding sites is not unusual. Often, ranking protocols are based on initial clustering of docked poses followed by the application of an energy function to rank each cluster according to its lowest energy member. Here, we present an approach of cluster ranking based not only on one molecular descriptor (e.g., an energy function) but also employing a large number of descriptors that are integrated in a machine learning model, whereby, an extremely randomized tree classifier based on 109 molecular descriptors is trained. The protocol is based on first locally enriching clusters with additional poses, the clusters are then characterized using features describing the distribution of molecular descriptors within the cluster, which are combined into a pairwise cluster comparison model to discriminate near-native from incorrect clusters. The results show that our approach is able to identify clusters containing near-native protein-protein complexes. In addition, we present an analysis of the descriptors with respect to their power to discriminate near native from incorrect clusters and how data transformations and recursive feature elimination can improve the ranking performance. Proteins 2017; 85:528-543. © 2016 Wiley Periodicals, Inc.

  14. Synthesis, characterization, biological studies (DNA binding, cleavage, antibacterial and topoisomerase I) and molecular docking of copper(II) benzimidazole complexes.

    Science.gov (United States)

    Arjmand, Farukh; Parveen, Shazia; Afzal, Mohd; Shahid, Mohd

    2012-09-03

    To explore the therapeutic potential of copper-based benzimidazole complexes, tetranuclear Cu(II) complex 1 and dinuclear ternary amino acid complexes 2 and 3 {L-trp and L-val, respectively} were synthesized and thoroughly characterized. In vitro DNA binding studies of complexes 1-3 were carried out employing UV-vis titrations, fluorescence, circular dichroic and viscosity measurements which revealed that the complexes 1-3 bind to CT DNA preferably via groove binding. Complex 1 cleaved pBR322 DNA via hydrolytic pathway (validated by T4 DNA ligase assay), accessible to major groove while 2 followed oxidative mechanism, binding to minor groove of DNA double helix; binding events were further validated by molecular docking studies. Additionally, the complexes 1 and 2 exhibit high Topo-I inhibitory activity at different concentrations. The complexes 1-3 were evaluated for antibacterial activity against Escherichia coli and Staphylococcus aureus, and 2 was found to be most effective against Gram-positive bacteria.

  15. Spectroscopic and molecular docking studies on the interaction of human serum albumin with copper(II) complexes

    Science.gov (United States)

    Guhathakurta, Bhargab; Pradhan, Ankur Bikash; Das, Suman; Bandyopadhyay, Nirmalya; Lu, Liping; Zhu, Miaoli; Naskar, Jnan Prakash

    2017-02-01

    Two osazone based ligands, butane-2,3-dione bis(2‧-pyridylhydrazone) (BDBPH) and hexane-3,4-dione bis(2‧-pyridylhydrazone) (HDBPH), were synthesized out of the 2:1 M Schiff base condensation of 2-hydrazino pyridine respectively with 2,3-butanedione and 3,4-hexanedione. The X-ray crystal structures of both the ligands have been determined. The copper(II) complex of HDBPH has also been synthesized and structurally characterized. HDBPH and its copper(II) complex have thoroughly been characterized through various spectroscopic and analytical techniques. The X-ray crystal structure of the copper complex of HDBPH shows that it is a monomeric Cu(II) complex having 'N4O2' co-ordination chromophore. Interaction of human serum albumin (HSA) with these ligands and their monomeric copper(II) complexes have been studied by various spectroscopic means. The experimental findings show that the ligands as well as their copper complexes are good HSA binders. Molecular docking investigations have also been done to unravel the mode of binding of the species with HSA.

  16. Synthesis, complexation, and fluorescence behavior of armed crown ethers carrying naphthyl group.

    Science.gov (United States)

    Kubo, K; Sakaguchi, S; Sakurai, T

    1999-07-12

    Armed crown ethers (1-4) bonding through an amine, amide, ether, or ester linkage to naphthyl group were found to display unique photophysical properties in the presence of guest salts. Complexation of PET fluoroionophores (1a and 1b) with Zn(2+) increased the fluorescence intensities of the host by a factor of 2.4 and 2.7, respectively. (1)H and (13)C NMR analyses of this complexation behavior of 1a revealed that Zn(2+) strongly coordinates with the armed crown nitrogen to cause a dramatic decrease in an intramolecular charge-transfer character. The armed crowns (2 and 3), bonding through an ether or ester linkage to a naphthalene, gave fluorescence quenching with guest thiocyanates. While the amide derivative (4) exhibited high Ba(2+) fluorescence selectivity and in the presence of this cation the host fluorescence intensity was by a factor of 3.69.

  17. Hydrogenation of esters catalyzed by ruthenium PN3-Pincer complexes containing an aminophosphine arm

    KAUST Repository

    Chen, Tao

    2014-08-11

    Hydrogenation of esters under mild conditions was achieved using air-stable ruthenium PN3-pincer complexes containing an aminophosphine arm. High efficiency was achieved even in the presence of water. DFT studies suggest a bimolecular proton shuttle mechanism which allows H2 to be activated by the relatively stable catalyst with a reasonably low transition state barrier. © 2014 American Chemical Society.

  18. Synthesis and luminescence properties of lanthanide complexes with a new tripodal ligands featuring salicylamide arms.

    Science.gov (United States)

    Song, Xue-Qin; Dong, Wen-Kui; Zhang, Yu-Jie; Liu, Wei-Sheng

    2010-01-01

    A series of luminescent lanthanide complexes with a new tripodal ligand featuring salicylamide arms, 2,2',2''-nitrilotris(2-furfurylaminoformylphenoxy)triethylamine (L), were synthesized and characterized by elemental analysis, IR and molar conductivity measurements. Photophysical properties of the complexes were studied by means of UV-vis absorption and steady-state luminescence spectroscopy. Excited-state luminescence lifetimes and quantum yield of the complexes were determined. Luminescence studies demonstrated that the tripodal ligand featuring salicylamide arms exhibits a good antennae effect with respect to the Tb(III) and Dy(III) ion due to efficient intersystem crossing and ligand to metal energy transfer. From a more general perspective, this work offers interesting perspectives for the development of efficient luminescent stains and enlarges the arsenal for developing novel luminescent lanthanide complexes of salicylamide derivatives.

  19. Phosphoregulation of an Inner Dynein Arm Complex in Chlamydomonas reinhardtii Is Altered in Phototactic Mutant Strains

    Science.gov (United States)

    King, Stephen J.; Dutcher, Susan K.

    1997-01-01

    To gain a further understanding of axonemal dynein regulation, mutant strains of Chlamydomonas reinhardtii that had defects in both phototactic behavior and flagellar motility were identified and characterized. ptm1, ptm2, and ptm3 mutant strains exhibited motility phenotypes that resembled those of known inner dynein arm region mutant strains, but did not have biochemical or genetic phenotypes characteristic of other inner dynein arm mutations. Three other mutant strains had defects in the f class of inner dynein arms. Dynein extracts from the pf9-4 strain were missing the entire f complex. Strains with mutations in pf9/ida1, ida2, or ida3 failed to assemble the f dynein complex and did not exhibit phototactic behavior. Fractionated dynein from mia1-1 and mia2-1 axonemes exhibited a novel f class inner dynein arm biochemical phenotype; the 138-kD f intermediate chain was present in altered phosphorylation forms. In vitro axonemal dynein activity was reduced by the mia1-1 and mia2-1 mutations. The addition of kinase inhibitor restored axonemal dynein activity concomitant with the dephosphorylation of the 138-kD f intermediate chain. Dynein extracts from uni1-1 axonemes, which specifically assemble only one of the two flagella, contained relatively high levels of the altered phosphorylation forms of the 138-kD intermediate chain. We suggest that the f dynein complex may be phosphoregulated asymmetrically between the two flagella to achieve phototactic turning. PMID:9008712

  20. Low abundance of the matrix arm of complex I in mitochondria predicts longevity in mice.

    Science.gov (United States)

    Miwa, Satomi; Jow, Howsun; Baty, Karen; Johnson, Amy; Czapiewski, Rafal; Saretzki, Gabriele; Treumann, Achim; von Zglinicki, Thomas

    2014-05-12

    Mitochondrial function is an important determinant of the ageing process; however, the mitochondrial properties that enable longevity are not well understood. Here we show that optimal assembly of mitochondrial complex I predicts longevity in mice. Using an unbiased high-coverage high-confidence approach, we demonstrate that electron transport chain proteins, especially the matrix arm subunits of complex I, are decreased in young long-living mice, which is associated with improved complex I assembly, higher complex I-linked state 3 oxygen consumption rates and decreased superoxide production, whereas the opposite is seen in old mice. Disruption of complex I assembly reduces oxidative metabolism with concomitant increase in mitochondrial superoxide production. This is rescued by knockdown of the mitochondrial chaperone, prohibitin. Disrupted complex I assembly causes premature senescence in primary cells. We propose that lower abundance of free catalytic complex I components supports complex I assembly, efficacy of substrate utilization and minimal ROS production, enabling enhanced longevity.

  1. A combined spectroscopic, docking and molecular dynamics simulation approach to probing binding of a Schiff base complex to human serum albumin.

    Science.gov (United States)

    Fani, N; Bordbar, A K; Ghayeb, Y

    2013-02-15

    The molecular mechanism of a Schiff base complex ((E)-((E)-2-(3-((E)-((E)-3(mercapto (methylthio) methylene)cyclopentylidene) amino) propylimino) cyclopentylidene) (methylthio) methanethiol) binding to Human Serum Albumin (HSA) was investigated by fluorescence quenching, absorption spectroscopy, molecular docking and molecular dynamics (MD) simulation procedures. The fluorescence emission of HSA was quenched by this Schiff base complex that has been analyzed for estimation of binding parameters. The titration of Schiff base solution by various amount of HSA was also followed by UV-Vis absorption spectroscopy and the corresponding data were analyzed by suitable models. The results revealed that this Schiff base has an ability to bind strongly to HSA and formed 1:1 complex. Energy transfer mechanism of quenching was discussed and the value of 5.45 ± 0.06 nm was calculated as the mean distance between the bound complex and the Trp residue. This is implying the high possibility of energy transfer from HSA to this Schiff base complex. Molecular docking results indicated that the main active binding site for this Schiff base complex is site III in subdomain IB. Moreover, MD simulation results suggested that this Schiff base complex can interact with HSA, without affecting the secondary structure of HSA but probably with a slight modification of its tertiary structure. MD simulations, molecular docking and experimental data reciprocally supported each other.

  2. Novel water-soluble fisetin/cyclodextrins inclusion complexes: Preparation, characterization, molecular docking and bioavailability.

    Science.gov (United States)

    Zhang, Jian-qiang; Jiang, Kun-ming; An, Kun; Ren, Si-hao; Xie, Xiao-guang; Jin, Yi; Lin, Jun

    2015-12-11

    Novel water-soluble inclusion complexes for fisetin (FIT) were developed by introducing β-cyclodextrin (β-CD) and γ-CD. Properties of the obtained complexes, as well as the interactions between each component, were systematically investigated in both solution and solid states by means of ESI-MS, NMR, FT-IR, XRD, DSC, SEM etc. All characterization information demonstrated that FIT/CDs inclusion complexes were formed, and exhibited different spectroscopic features and properties from FIT. A complex with 1:1 stoichiometry of FIT and CDs was confirmed with Job's method. Meanwhile, as supported by molecular modeling calculations, we suggested that phenyl group (C ring) of FIT molecule was included in the CDs cavity from the wide side. Moreover, the water solubility of FIT/CDs was successfully improved from 2.8 mg/mL (in ethanol aqueous solution) to 4.5 mg/mL (FIT/β-CD complex) and 7.8 mg/mL (FIT/γ-CD complex), and higher thermal stability results were shown by thermal analysis for those complexes. Notably, the inclusion complexes displayed almost two times higher cytotoxicity compared to free FIT against Hela and MCF-7 cells. These results suggested that FIT/CDs complexes could be potentially useful in food industry and healthcare area.

  3. Failure of Arm Movement Control in Stroke Patients, Characterized by Loss of Complexity.

    Directory of Open Access Journals (Sweden)

    Segun Goh

    Full Text Available We study the mechanism of human arm-posture control by means of nonlinear dynamics and quantitative time series analysis methods. Utilizing linear and nonlinear measures in combination, we find that pathological tremors emerge in patient dynamics and serve as a main feature discriminating between normal and patient groups. The deterministic structure accompanied with loss of complexity inherent in the tremor dynamics is also revealed. To probe the underlying mechanism of the arm-posture dynamics, we further analyze the coupling patterns between joints and components, and discuss their roles in breaking of the organization structure. As a result, we elucidate the mechanisms in the arm-posture dynamics of normal subjects responding to the gravitational force and for the reduction of the dynamic degrees of freedom in the patient dynamics. This study provides an integrated framework for the origin of the loss of complexity in the dynamics of patients as well as the coupling structure in the arm-posture dynamics.

  4. Cobalt (II) complex with novel unsymmetrical tetradentate Schiff base (ON) ligand: in vitro cytotoxicity studies of complex, interaction with DNA/protein, molecular docking studies, and antibacterial activity.

    Science.gov (United States)

    Shokohi-Pour, Zahra; Chiniforoshan, Hossein; Sabzalian, Mohammad R; Esmaeili, Seyed-Alireza; Momtazi-Borojeni, Amir Abbas

    2017-03-08

    [C20H17N3O2] and cobalt (II) complex [Co(L(2))(MeOH)2].ClO4, (L(2) = 4-((E)-1-((2-(((E)-pyridin-2-ylmethylene) amino) phenyl) imino) ethyl) benzene-1, 3-diol) novel Schiff base has been synthesiszed and chracterized by Fourier transform infrared, UV-vis, (1)H-NMR spectroscopy, and elemental analysis techniques. The interaction of Co(II) complex with DNA and BSA was investigated by electronic absorption spectroscopy, fluorescence spectroscopy, circular dichroism, and thermal denaturation studies. Our experiments indicate that this complex could strongly bind to CT-DNA via minor groove mechanism. In addition, fluorescence spectrometry of BSA with the complex showed that the fluorescence quenching mechanism of BSA was of static type. The complex exhibited significant in vitro cytotoxicity against three human cancer cell lines (JURKAT, SKOV3, and U87). The molecular docking experiment effectively proved the binding of complex to DNA and BSA. Finally, antibacterial assay over gram-positive and gram-negative pathogenic bacterial strains was studied.

  5. A python-based docking program utilizing a receptor bound ligand shape: PythDock.

    Science.gov (United States)

    Chung, Jae Yoon; Cho, Seung Joo; Hah, Jung-Mi

    2011-09-01

    PythDock is a heuristic docking program that uses Python programming language with a simple scoring function and a population based search engine. The scoring function considers electrostatic and dispersion/repulsion terms. The search engine utilizes a particle swarm optimization algorithm. A grid potential map is generated using the shape information of a bound ligand within the active site. Therefore, the searching area is more relevant to the ligand binding. To evaluate the docking performance of PythDock, two well-known docking programs (AutoDock and DOCK) were also used with the same data. The accuracy of docked results were measured by the difference of the ligand structure between x-ray structure, and docked pose, i.e., average root mean squared deviation values of the bound ligand were compared for fourteen protein-ligand complexes. Since the number of ligands' rotational flexibility is an important factor affecting the accuracy of a docking, the data set was chosen to have various degrees of flexibility. Although PythDock has a scoring function simpler than those of other programs (AutoDock and DOCK), our results showed that PythDock predicted more accurate poses than both AutoDock4.2 and DOCK6.2. This indicates that PythDock could be a useful tool to study ligand-receptor interactions and could also be beneficial in structure based drug design.

  6. Structure prediction of LDLR-HNP1 complex based on docking enhanced by LDLR binding 3D motif.

    Science.gov (United States)

    Esmaielbeiki, Reyhaneh; Naughton, Declan P; Nebel, Jean-Christophe

    2012-04-01

    Human antimicrobial peptides (AMPs), including defensins, have come under intense scrutiny owing to their key multiple roles as antimicrobial agents. Not only do they display direct action on microbes, but also recently they have been shown to interact with the immune system to increase antimicrobial activity. Unfortunately, since mechanisms involved in the binding of AMPs to mammalian cells are largely unknown, their potential as novel anti-infective agents cannot be exploited yet. Following the reported interaction of Human Neutrophil Peptide 1 dimer (HNP1) with a low density lipoprotein receptor (LDLR), a computational study was conducted to discover their putative mode of interaction. State-of-the-art docking software produced a set of LDLR-HNP1 complex 3D models. Creation of a 3D motif capturing atomic interactions of the LDLR binding interface allowed selection of the most plausible configurations. Eventually, only two models were in agreement with the literature. Binding energy estimations revealed that only one of them is particularly stable, but also interaction with LDLR weakens significantly bonds within the HNP1 dimer. This may be significant since it suggests a mechanism for internalisation of HNP1 in mammalian cells. In addition to a novel approach for complex structure prediction, this study proposes a 3D model of the LDLR-HNP1 complex which highlights the key residues which are involved in the interactions. The putative identification of the receptor binding mechanism should inform the future design of synthetic HNPs to afford maximum internalisation, which could lead to novel anti-infective drugs.

  7. Comparing the Suitability of Autodock, Gold and Glide for the Docking and Predicting the Possible Targets of Ru(II-Based Complexes as Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Adebayo A. Adeniyi

    2013-03-01

    Full Text Available In cancer chemotherapy, metal-based complexes have been recognized as the most promising means of inhibiting cancer growth due to the successful application of cis-platin and its derivatives above many of the existing organic anticancer agents. The limitations in their rational design can be traced to the complexity of the mechanism of their operations, lack of proper knowledge of their targets and lack of force fields in docking packages to appropriately define the metal centre of the organometallic complexes. In this paper, some of the promising anticancer complexes of Ru(II such as the rapta-based complexes formulated as [Ru(η6-p-cymeneL2(pta] and those with unusual ligands are considered. CatB and kinases which have been experimentally confirmed as possible targets of the complexes are also predicted by the three methods as one of the most targeted receptors while TopII and HDAC7 are predicted by two and one of the methods as best targets. The interesting features of the binding of the complexes show that some of the complexes preferentially target specific macromolecules than the others, which is an indication of their specificity and possibility of their therapeutic combination without severe side effects that may come from competition for the same target. Also, introduction of unusual ligands is found to significantly improve the activities of most of the complexes studied. Strong correlations are observed for the predicted binding sites and the orientation of the complexes within the binding site by the three methods of docking. However there are disparities in the ranking of the complexes by the three method of docking, especially that of Glide.

  8. The Development of Bispecific Hexavalent Antibodies as a Novel Class of DOCK-AND-LOCKTM (DNLTM Complexes

    Directory of Open Access Journals (Sweden)

    Chien-Hsing Chang

    2013-05-01

    Full Text Available The DOCK-AND-LOCKTM (DNLTM method provides a modular approach to develop multivalent, multifunctional complexes of defined structures, of which bispecific hexavalent antibodies (bsHexAbs are prominent examples with potential applications in targeted therapy for malignant, autoimmune, and infectious diseases. Currently, bsHexAbs are constructed by derivatizing a divalent IgG, at the carboxyl termini of either the heavy chain (the CH3-format or the light chain (the Ck-format, to contain two stabilized dimers of Fab having a different specificity from the IgG. In this review, we briefly outline the features of the DNLTM method and describe key aspects of bsHexAbs examined with diverse preclinical studies, which include binding affinity to target cells, induction of signaling pathways, effector functions, serum stability, pharmacokinetics, and antitumor activity in human tumor xenograft models. Our findings favor the selection of the CK- over the CH3-format for further exploration of bsHexAbs in clinical trials.

  9. DockingShop: A Tool for Interactive Molecular Docking

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Ting-Cheng; Max, Nelson L.; Ding, Jinhui; Bethel, E. Wes; Crivelli, Silvia N.

    2005-04-24

    Given two independently determined molecular structures, the molecular docking problem predicts the bound association, or best fit between them, while allowing for conformational changes of the individual molecules during construction of a molecular complex. Docking Shop is an integrated environment that permits interactive molecular docking by navigating a ligand or protein to an estimated binding site of a receptor with real-time graphical feedback of scoring factors as visual guides. Our program can be used to create initial configurations for a protein docking prediction process. Its output--the structure of aprotein-ligand or protein-protein complex--may serve as an input for aprotein docking algorithm, or an optimization process. This tool provides molecular graphics interfaces for structure modeling, interactive manipulation, navigation, optimization, and dynamic visualization to aid users steer the prediction process using their biological knowledge.

  10. A combined atomic force microscopy imaging and docking study to investigate the complex between p53 DNA binding domain and Azurin.

    Science.gov (United States)

    Bizzarri, Anna Rita; Di Agostino, Silvia; Andolfi, Laura; Cannistraro, Salvatore

    2009-01-01

    The tumor suppressor p53 interacts with the redox copper protein Azurin (AZ) forming a complex which is of some relevance in biomedicine and cancer therapy. To obtain information on the spatial organization of this complex when it is immobilized on a substrate, we have used tapping mode-atomic force microscopy (TM-AFM) imaging combined with computational docking. The vertical dimension and the bearing volume of the DNA binding domain (DBD) of p53, anchored to functionalized gold substrate through exposed lysine residues, alone and after deposing AZ, have been measured by TM-AFM. By a computational docking approach, a three-dimensional model for the DBD of p53, before and after addition of AZ, have been predicted. Then we have calculated the possible arrangements of these biomolecular systems on gold substrate by finding a good agreement with the related experimental distribution of the height. The potentiality of the approach combining TM-AFM imaging and computational docking for the study of biomolecular complexes immobilized on substrates is briefly discussed.

  11. Hardware-Software Complex for Functional and Parametric Tests of ARM Microcontrollers STM32F1XX

    Directory of Open Access Journals (Sweden)

    Egorov Aleksey

    2016-01-01

    Full Text Available The article presents the hardware-software complex for functional and parametric tests of ARM microcontrollers STM32F1XX. The complex is based on PXI devices by National Instruments and LabVIEW software environment. Data exchange procedure between a microcontroller under test and the complex hardware is describes. Some test results are also presented.

  12. Synthesis, molecular docking and evaluation of antifungal activity of Ni(II), Co(II) and Cu(II) complexes of porphyrin core macromolecular ligand.

    Science.gov (United States)

    Singh, Urvashi; Malla, Ali Mohammad; Bhat, Imtiyaz Ahmad; Ahmad, Ajaz; Bukhari, Mohd Nadeem; Bhat, Sneha; Anayutullah, Syed; Hashmi, Athar Adil

    2016-04-01

    Porphyrin core dendrimeric ligand (L) was synthesized by Rothemund synthetic route in which p-hydroxy benzaldehyde and pyrrole were fused together. The prepared ligand was complexed with Ni(II), Cu(II) and Co(II) ions, separately. Both the ligand and its complexes were characterized by elemental analysis and spectroscopic studies (FT-IR, UV-Vis, (1)HNMR). Square planar geometries were proposed for Cu(II), Ni(II) and Co(II) ions in cobalt, Nickel and copper complexes, respectively on the basis of UV-Vis spectroscopic data. The ligand and its complex were screened on Candida albicans (ATCC 10231), Aspergillus fumigatus (ATCC 1022), Trichophyton mentagrophytes (ATCC 9533) and Pencillium marneffei by determining MICs and inhibition zones. The activity of the ligand and its complexes was found to be in the order: CuL ˃ CoL ≈ NiL ˃ L. Detection of DNA damage at the level of the individual eukaryotic cell was observed by commet assay. Molecular docking technique was used to understand the ligand-DNA interactions. From docking experiment, we conclude that copper complex interacts more strongly than rest two.

  13. Delineation of the complement receptor type 2-C3d complex by site-directed mutagenesis and molecular docking.

    Science.gov (United States)

    Shaw, Craig D; Storek, Michael J; Young, Kendra A; Kovacs, James M; Thurman, Joshua M; Holers, V Michael; Hannan, Jonathan P

    2010-12-10

    The interactions between the complement receptor type 2 (CR2) and the C3 complement fragments C3d, C3dg, and iC3b are essential for the initiation of a normal immune response. A crystal-derived structure of the two N-terminal short consensus repeat (SCR1-2) domains of CR2 in complex with C3d has previously been elucidated. However, a number of biochemical and biophysical studies targeting both CR2 and C3d appear to be in conflict with these structural data. Previous mutagenesis and heteronuclear NMR spectroscopy studies directed toward the C3d-binding site on CR2 have indicated that the CR2-C3d cocrystal structure may represent an encounter/intermediate or nonphysiological complex. With regard to the CR2-binding site on C3d, mutagenesis studies by Isenman and coworkers [Isenman, D. E., Leung, E., Mackay, J. D., Bagby, S. & van den Elsen, J. M. H. (2010). Mutational analyses reveal that the staphylococcal immune evasion molecule Sbi and complement receptor 2 (CR2) share overlapping contact residues on C3d: Implications for the controversy regarding the CR2/C3d cocrystal structure. J. Immunol. 184, 1946-1955] have implicated an electronegative "concave" surface on C3d in the binding process. This surface is discrete from the CR2-C3d interface identified in the crystal structure. We generated a total of 18 mutations targeting the two (X-ray crystallographic- and mutagenesis-based) proposed CR2 SCR1-2 binding sites on C3d. Using ELISA analyses, we were able to assess binding of mutant forms of C3d to CR2. Mutations directed toward the concave surface of C3d result in substantially compromised CR2 binding. By contrast, targeting the CR2-C3d interface identified in the cocrystal structure and the surrounding area results in significantly lower levels of disruption in binding. Molecular modeling approaches used to investigate disparities between the biochemical data and the X-ray structure of the CR2-C3d cocrystal result in highest-scoring solutions in which CR2 SCR1-2 is

  14. Modeling holo-ACP:DH and holo-ACP:KR complexes of modular polyketide synthases: a docking and molecular dynamics study

    Directory of Open Access Journals (Sweden)

    Anand Swadha

    2012-05-01

    Full Text Available Abstract Background Modular polyketide synthases are multifunctional megasynthases which biosynthesize a variety of secondary metabolites using various combinations of dehydratase (DH, ketoreductase (KR and enoyl-reductase (ER domains. During the catalysis of various reductive steps these domains act on a substrate moiety which is covalently attached to the phosphopantetheine (P-pant group of the holo-Acyl Carrier Protein (holo-ACP domain, thus necessitating the formation of holo-ACP:DH and holo-ACP:KR complexes. Even though three dimensional structures are available for DH, KR and ACP domains, no structures are available for DH or KR domains in complex with ACP or substrate moieties. Since Ser of holo-ACP is covalently attached to a large phosphopantetheine group, obtaining complexes involving holo-ACP by standard protein-protein docking has been a difficult task. Results We have modeled the holo-ACP:DH and holo-ACP:KR complexes for identifying specific residues on DH and KR domains which are involved in interaction with ACP, phosphopantetheine and substrate moiety. A novel combination of protein-protein and protein-ligand docking has been used to first model complexes involving apo-ACP and then dock the phosphopantetheine and substrate moieties using covalent connectivity between ACP, phosphopantetheine and substrate moiety as constraints. The holo-ACP:DH and holo-ACP:KR complexes obtained from docking have been further refined by restraint free explicit solvent MD simulations to incorporate effects of ligand and receptor flexibilities. The results from 50 ns MD simulations reveal that substrate enters into a deep tunnel in DH domain while in case of KR domain the substrate binds a shallow surface exposed cavity. Interestingly, in case of DH domain the predicted binding site overlapped with the binding site in the inhibitor bound crystal structure of FabZ, the DH domain from E.Coli FAS. In case of KR domain, the substrate binding site

  15. Involvement of Complexin 2 in Docking, Locking and Unlocking of Different SNARE Complexes during Sperm Capacitation and Induced Acrosomal Exocytosis.

    NARCIS (Netherlands)

    Tsai, P.S.; Brewis, I.A.; van Maaren, J.; Gadella, B.M.

    2012-01-01

    Acrosomal exocytosis (AE) is an intracellular multipoint fusion reaction of the sperm plasma membrane (PM) with the outer acrosomal membrane (OAM). This unique exocytotic event enables the penetration of the sperm through the zona pellucida of the oocyte. We previously observed a stable docking of O

  16. Prediction of homoprotein and heteroprotein complexes by protein docking and template-based modeling : A CASP-CAPRI experiment

    NARCIS (Netherlands)

    Lensink, Marc F.; Velankar, Sameer; Kryshtafovych, Andriy; Huang, Shen You; Schneidman-Duhovny, Dina; Sali, Andrej; Segura, Joan; Fernandez-Fuentes, Narcis; Viswanath, Shruthi; Elber, Ron; Grudinin, Sergei; Popov, Petr; Neveu, Emilie; Lee, Hasup; Baek, Minkyung; Park, Sangwoo; Heo, Lim; Rie Lee, Gyu; Seok, Chaok; Qin, Sanbo; Zhou, Huan Xiang; Ritchie, David W.; Maigret, Bernard; Devignes, Marie Dominique; Ghoorah, Anisah; Torchala, Mieczyslaw; Chaleil, Raphaël A G; Bates, Paul A.; Ben-Zeev, Efrat; Eisenstein, Miriam; Negi, Surendra S.; Weng, Zhiping; Vreven, Thom; Pierce, Brian G.; Borrman, Tyler M.; Yu, Jinchao; Ochsenbein, Françoise; Guerois, Raphaël; Vangone, Anna; Garcia Lopes Maia Rodrigues, João; van Zundert, Gydo; Nellen, Mehdi; Xue, Li; Karaca, Ezgi; Melquiond, Adrien S J; Visscher, Koen; Kastritis, Panagiotis L.; Bonvin, Alexandre M J J; Xu, Xianjin; Qiu, Liming; Yan, Chengfei; Li, Jilong; Ma, Zhiwei; Cheng, Jianlin; Zou, Xiaoqin; Shen, Yang; Peterson, Lenna X.; Kim, Hyung Rae; Roy, Amit; Han, Xusi; Esquivel-Rodriguez, Juan; Kihara, Daisuke; Yu, Xiaofeng; Bruce, Neil J.; Fuller, Jonathan C.; Wade, Rebecca C.; Anishchenko, Ivan; Kundrotas, Petras J.; Vakser, Ilya A.; Imai, Kenichiro; Yamada, Kazunori; Oda, Toshiyuki; Nakamura, Tsukasa; Tomii, Kentaro; Pallara, Chiara; Romero-Durana, Miguel; Jiménez-García, Brian; Moal, Iain H.; Férnandez-Recio, Juan; Joung, Jong Young; Kim, Jong Yun; Joo, Keehyoung; Lee, Jooyoung; Kozakov, Dima; Vajda, Sandor; Mottarella, Scott; Hall, David R.; Beglov, Dmitri; Mamonov, Artem; Xia, Bing; Bohnuud, Tanggis; Del Carpio, Carlos A.; Ichiishi, Eichiro; Marze, Nicholas; Kuroda, Daisuke; Roy Burman, Shourya S.; Gray, Jeffrey J.; Chermak, Edrisse; Cavallo, Luigi; Oliva, Romina; Tovchigrechko, Andrey; Wodak, Shoshana J.

    2016-01-01

    We present the results for CAPRI Round 30, the first joint CASP-CAPRI experiment, which brought together experts from the protein structure prediction and protein-protein docking communities. The Round comprised 25 targets from amongst those submitted for the CASP11 prediction experiment of 2014. Th

  17. Manipulability measure of dual-arm space robot and its application to design an optimal configuration

    Science.gov (United States)

    Zhang, Bo; Liang, Bin; Wang, Xueqian; Li, Gang; Chen, Zhang; Zhu, Xiaojun

    2016-11-01

    Coupling effect exists among different arms and the base in a multi-arm space robot. The manipulability measure of one arm can be affected by the base and the other arms, which has important effects on the configuration optimization, the singularity avoidance and the compliant control. The manipulability measure for a multi-arm space robot is more complex than that of a single-arm space robot. At present, the manipulability measure of a multi-arm space robot has not been studied. In the paper, a new concept of manipulability measure is applied to analyze the manipulability measure for a dual-arm space robot, especially for the manipulability measure of the mission arm subjecting to the influence from coupling effect of auxiliary arm and the base. Based on the manipulability measure of mission arm, a performance index is introduced and used to design and choose an optimization configuration for a dual-arm space robot. Finally, a plane dual-arm space robot is simulated, which is illustrated the influence of joint angles and the base attitude on mission arm's manipulability measure. Simulation results show that the proposed manipulability measure is useful for a multi-arm space robot and optimal configuration can be extended and applied to the coordinated soft rendezvous and docking and the target capture in the field of on-orbit servicing.

  18. Synthesis, spectroscopic characterization, potentiometric studies, cytotoxic studies and molecular docking studies of DNA binding of transition metal complexes with 1,1-diaminopropane-Schiff base

    Science.gov (United States)

    Alaghaz, Abdel-Nasser M. A.; El-Sayed, Badr A.; El-Henawy, Ahmed A.; Ammar, Reda A. A.

    2013-03-01

    A new series of Schiff base transition metal complexes with N,N'-bis(2-hydroxybenzylidene)-1,1-diaminopropane (H2BHBDAP) have been prepared and characterized by elemental analysis, spectroscopic and magnetic measurements. Protonation constants of Schiff base and stability constants of their binary metal complexes have been determined potentiometrically in 50% DMSO-water media at 25 °C and ionic strength 0.10 M sodium perchlorate. Quantum chemical calculations were performed with semi-empirical method to find the optimum geometry of the ligand and its complexes. Additionally in silico, the Docking studies and the calculated pharmacokinetic parameters show promising futures for application of the ligand and complexes as high potency agents for DNA binding activity.

  19. Application of a Dual-Arm Robot in Complex Sample Preparation and Measurement Processes.

    Science.gov (United States)

    Fleischer, Heidi; Drews, Robert Ralf; Janson, Jessica; Chinna Patlolla, Bharath Reddy; Chu, Xianghua; Klos, Michael; Thurow, Kerstin

    2016-10-01

    Automation systems with applied robotics have already been established in industrial applications for many years. In the field of life sciences, a comparable high level of automation can be found in the areas of bioscreening and high-throughput screening. Strong deficits still exist in the development of flexible and universal fully automated systems in the field of analytical measurement. Reasons are the heterogeneous processes with complex structures, which include sample preparation and transport, analytical measurements using complex sensor systems, and suitable data analysis and evaluation. Furthermore, the use of nonstandard sample vessels with various shapes and volumes results in an increased complexity. The direct use of existing automation solutions from bioscreening applications is not possible. A flexible automation system for sample preparation, analysis, and data evaluation is presented in this article. It is applied for the determination of cholesterol in biliary endoprosthesis using gas chromatography-mass spectrometry (GC-MS). A dual-arm robot performs both transport and active manipulation tasks to ensure human-like operation. This general robotic concept also enables the use of manual laboratory devices and equipment and is thus suitable in areas with a high standardization grade.

  20. Complex wireframe DNA origami nanostructures with multi-arm junction vertices.

    Science.gov (United States)

    Zhang, Fei; Jiang, Shuoxing; Wu, Siyu; Li, Yulin; Mao, Chengde; Liu, Yan; Yan, Hao

    2015-09-01

    Structural DNA nanotechnology and the DNA origami technique, in particular, have provided a range of spatially addressable two- and three-dimensional nanostructures. These structures are, however, typically formed of tightly packed parallel helices. The development of wireframe structures should allow the creation of novel designs with unique functionalities, but engineering complex wireframe architectures with arbitrarily designed connections between selected vertices in three-dimensional space remains a challenge. Here, we report a design strategy for fabricating finite-size wireframe DNA nanostructures with high complexity and programmability. In our approach, the vertices are represented by n × 4 multi-arm junctions (n = 2-10) with controlled angles, and the lines are represented by antiparallel DNA crossover tiles of variable lengths. Scaffold strands are used to integrate the vertices and lines into fully assembled structures displaying intricate architectures. To demonstrate the versatility of the technique, a series of two-dimensional designs including quasi-crystalline patterns and curvilinear arrays or variable curvatures, and three-dimensional designs including a complex snub cube and a reconfigurable Archimedean solid were constructed.

  1. Synthesis, structure, biochemical, and docking studies of a new dinitrosyl iron complex [Fe2(μ-SC4H3SCH2)2(NO)4

    Science.gov (United States)

    Davidovich, P. B.; Fischer, A. I.; Korchagin, D. V.; Panchuk, V. V.; Shchukarev, A. V.; Garabadzhiu, A. V.; Belyaev, A. N.

    2015-07-01

    A new dinitrosyl iron complex of binuclear structure [Fe2(μ-S-2-methylthiophene)2(NO)4] was first synthesized and structurally characterized by XRD and theoretical methods. Using caspase-3 as an example it was shown that [Fe2(μ-S-2-methylthiophene)2(NO)4] and its analog [Fe2(μ-S-2-methylfurane)2(NO)4] can inhibit the action of active site cysteine proteins; the difference in inhibitory activity was explained by molecular docking studies. Biochemical and in silico studies give grounds that the biological activity of dinitrosyl iron complexes is a μ-SR bridging ligand structure function. Thus the rational design strategy of [Fe2(μ-SR)2(NO)4] complexes can be applied to make NO prodrugs with high affinity to therapeutically significant targets involved in cancer and inflammation.

  2. Quinoxaline based bio-active mixed ligand transition metal complexes: Synthesis, characterization, electrochemical, antimicrobial, DNA binding, cleavage, antioxidant and molecular docking studies.

    Science.gov (United States)

    Dhanaraj, C Justin; Johnson, Jijo

    2015-10-01

    Co(II), Ni(II), Cu(II) and Zn(II) mixed ligand complexes have been synthesized from N(2), N(3)-bis(4-nitrophenyl)quinoxaline-2,3-diamine and 1,10-phenanthroline. The compounds were characterized by elemental analyses, molar conductance, magnetic susceptibility, IR, UV-Vis., (1)H NMR, mass and ESR spectra. Octahedral geometry has been assigned for Co(II), Ni(II) and Zn(II) complexes and distorted octahedral geometry for Cu(II) complex. Electrochemical behavior of the synthesized complexes was studied using cyclic voltammetry. Grain size and surface morphologies of the complexes were determined by powder XRD and SEM analyses. The mixed ligand metal complexes were screened for antimicrobial activity against bacterial species Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus; fungal species Aspergillus niger, and Candida albicans by disc diffusion method. The DNA binding and DNA cleavage activities of the compounds were determined using electronic absorption titration and agarose gel electrophoresis respectively. The superoxide radical scavenging and free radical scavenging activities of the Cu(II) complex was also evaluated. Molecular docking studies of the synthesized mixed ligand metal complexes were carried out against B-DNA dodecamer and the protein Plasmodium falciparum dihydrofolate reductase (pf DHFR).

  3. Synthesis and spectral characterization of 2-((2-hydroxybenzylidene)amino)-2-methylpropane-1,3-diol derived complexes: Molecular docking and antimicrobial studies

    Science.gov (United States)

    Ansari, Istikhar A.; Sama, Farasha; Raizada, Mukul; Shahid, M.; Rajpoot, Ravi Kant; Siddiqi, Zafar A.

    2017-01-01

    A series of four homo-dinuclear transition metal complexes with stoichiometry [M2(HL)2(H2O)2] [M = Fe (1), Co (2), Ni (3) and Cu (4); H3L = 2-((2-hydroxybenzylidene)amino)-2-methylpropane-1,3-diol] has been prepared. Ligand (H3L) was obtained by the condensation of 2-amino-2-methyl-1,3-propanediol (H2ampd) with salicylaldehyde. The complexes (1-4) are characterized employing elemental analysis, FTIR, ESI mass, 1H &13C NMR, EPR, UV Visible, TGA, cyclic voltammetry, and magnetic studies. Spectral data ascertained the bonding features and the geometry of the complexes and revealed that all the complexes adopt distorted octahedral geometry with high spin state of metal ions. Thermal and ESI mass data confirmed the proposed stoichiometry of the complexes. Cyclic voltammetric (CV) studies ascertain the formation of MII/MIII quasi-reversible redox couples in solution. The antimicrobial activities of the present complexes have been examined against few bacteria (E. coli, B. subtilis, S. aureus and S. typhymurium) and fungi (C. albicans, A. fumigatus and P. marneffeiin) suggesting that the present compounds show moderate to high antimicrobial properties. Among all the compounds tested, complex (4) exhibited highest antibacterial as well as antifungal activity. Molecular docking studies of the free ligand and the complexes are performed with BDNA.

  4. Binding affinities of Schiff base Fe(II) complex with BSA and calf-thymus DNA: Spectroscopic investigations and molecular docking analysis.

    Science.gov (United States)

    Rudra, Suparna; Dasmandal, Somnath; Patra, Chiranjit; Kundu, Arjama; Mahapatra, Ambikesh

    2016-09-05

    The binding interaction of a synthesized Schiff base Fe(II) complex with biological macromolecules viz., bovine serum albumin (BSA) and calf thymus(ct)-DNA have been investigated using different spectroscopic techniques coupled with viscosity measurements at physiological pH and 298K. Regular amendments in emission intensities of BSA upon the action of the complex indicate significant interaction between them, and the binding interaction have been characterized by Stern Volmer plots and thermodynamic binding parameters. On the basis of this quenching technique one binding site with binding constant (Kb=(7.6±0.21)×10(5)) between complex and protein have been obtained at 298K. Time-resolved fluorescence studies have also been encountered to understand the mechanism of quenching induced by the complex. Binding affinities of the complex to the fluorophores of BSA namely tryptophan (Trp) and tyrosine (Tyr) have been judged by synchronous fluorescence studies. Secondary structural changes of BSA rooted by the complex has been revealed by CD spectra. On the other hand, hypochromicity of absorption spectra of the complex with the addition of ct-DNA and the gradual reduction in emission intensities of ethidium bromide bound ct-DNA in presence of the complex indicate noticeable interaction between ct-DNA and the complex with the binding constant (4.2±0.11)×10(6)M(-1). Life-time measurements have been studied to determine the relative amplitude of binding of the complex to ct-DNA base pairs. Mode of binding interaction of the complex with ct-DNA has been deciphered by viscosity measurements. CD spectra have also been used to understand the changes in ct-DNA structure upon binding with the metal complex. Density functional theory (DFT) and molecular docking analysis have been employed in highlighting the interactive phenomenon and binding location of the complex with the macromolecules.

  5. Binding affinities of Schiff base Fe(II) complex with BSA and calf-thymus DNA: Spectroscopic investigations and molecular docking analysis

    Science.gov (United States)

    Rudra, Suparna; Dasmandal, Somnath; Patra, Chiranjit; Kundu, Arjama; Mahapatra, Ambikesh

    2016-09-01

    The binding interaction of a synthesized Schiff base Fe(II) complex with biological macromolecules viz., bovine serum albumin (BSA) and calf thymus(ct)-DNA have been investigated using different spectroscopic techniques coupled with viscosity measurements at physiological pH and 298 K. Regular amendments in emission intensities of BSA upon the action of the complex indicate significant interaction between them, and the binding interaction have been characterized by Stern Volmer plots and thermodynamic binding parameters. On the basis of this quenching technique one binding site with binding constant (Kb = (7.6 ± 0.21) × 105) between complex and protein have been obtained at 298 K. Time-resolved fluorescence studies have also been encountered to understand the mechanism of quenching induced by the complex. Binding affinities of the complex to the fluorophores of BSA namely tryptophan (Trp) and tyrosine (Tyr) have been judged by synchronous fluorescence studies. Secondary structural changes of BSA rooted by the complex has been revealed by CD spectra. On the other hand, hypochromicity of absorption spectra of the complex with the addition of ct-DNA and the gradual reduction in emission intensities of ethidium bromide bound ct-DNA in presence of the complex indicate noticeable interaction between ct-DNA and the complex with the binding constant (4.2 ± 0.11) × 106 M- 1. Life-time measurements have been studied to determine the relative amplitude of binding of the complex to ct-DNA base pairs. Mode of binding interaction of the complex with ct-DNA has been deciphered by viscosity measurements. CD spectra have also been used to understand the changes in ct-DNA structure upon binding with the metal complex. Density functional theory (DFT) and molecular docking analysis have been employed in highlighting the interactive phenomenon and binding location of the complex with the macromolecules.

  6. Synthesis, characterization and studies on antioxidant and molecular docking of metal complexes of 1-(benzo[d]thiazol-2-yl)thiourea

    Indian Academy of Sciences (India)

    Harinath Yapati; Subba Rao Devineni; Suresh Chirumamilla; Seshaiah Kalluru

    2016-01-01

    In the present study, a new thiourea derivative bearing benzothiazole ligand, 1-(benzo[d]thiazol-2-yl)thiourea (btt) and its ternary metal (Cu(II), Co(II) and Ni(II)) complexes were synthesized. The structural characterization was carried out by micro analysis, IR, 1H-NMR, EPR, UV-Visible spectral analyses, molar conductance and thermal analysis studies. Spectral studies of complexes revealed that the metal complexes have distorted octahedral geometry. Molecular modelling study was performed to evaluate the recognition of target compounds at the 3MNG binding pocket. The docking results revealed that copper complex selectively binds to the crucial amino acid residues in the active site of 3MNG. The in vitro antioxidant activity of the ligand and its metal complexes was assayed by radical scavenging activity (DPPH, H2O2 and NO) and ferric reducing antioxidant power (FRAP) methods. The ligand showed moderate antioxidant activity whereas the metal complexes exhibited better antioxidant activity than that of the ligand. The results of the four methods proved that the copper complex is the most potent antioxidant among all the tested compounds.

  7. Synthesis, crystal structures, molecular docking, and in vitro biological activities evaluation of transition metal complexes with 4-(3,4-dichlorophenyl) piperazine-1-carboxylic acid

    Science.gov (United States)

    Chen, Zhi-Jian; Chen, Ya-Na; Xu, Chun-Na; Zhao, Shan-Shan; Cao, Qi-Yue; Qian, Shao-Song; Qin, Jie; Zhu, Hai-Liang

    2016-08-01

    Three novel mononuclear complexes, [MⅡ(L)2·2H2O], (M = Cu, Ni or Cd; HL = 4-(3,4-dichlorophenyl)piperazine-1-carboxylic acid)were synthesized and structurally determined by single-crystal X-ray diffraction. Molecular docking study preliminarily revealed that complex 1 had potential urease inhibitory activity. In accordance with the result of calculation, in vitro tests of the inhibitory activities of complexes 1-3 against jack bean urease showed complex 1 (IC50 = 8.17 ± 0.91 μM) had better inhibitory activities than the positive reference acetohydroxamic acid (AHA) (IC50 = 26.99 ± 1.43 μM), while complexes 2 and 3 showed no inhibitory activities., kinetics study was carried out to explore the mechanism of the inhibiting of the enzyme, and the result indicated that complex 1 was a competitive inhibitor of urease. Albumin binding experiment and in vitro toxicity evaluation of complex 1 were implemented to explore its Pharmacological properties.

  8. Newer mixed ligand Schiff base complexes from aquo-N-(2‧-hydroxy acetophenone) glycinatocopper(II) as synthon: DFT, antimicrobial activity and molecular docking study

    Science.gov (United States)

    Pramanik, Harun A. R.; Das, Dharitri; Paul, Pradip C.; Mondal, Paritosh; Bhattacharjee, Chira R.

    2014-02-01

    Synthesis of a series of newer mixed ligand copper(II) complexes of aminoacid Schiff base of the type [CuL(X)] (L = N-(2‧-hydroxy acetophenone) glycinate, X = imidazole (im) 2, benzimidazole (benz) 3, pyridine (py) 4, hydrazine (hz) 5,8-hydroxyquinoline (8-hq) 6, pyrrolidine (pyrr) 7, piperidine (pip) 8, and nicotinamide (nic) 9) have been accomplished from the interaction of an aquated Schiff base complex, [CuL(H2O)]·H2O, 1 with some selected neutral nitrogen-donor ligands. The copper(II) Schiff base complex, [CuL(H2O)]·H2O, L = N-(2‧-hydroxy acetophenone) glycinate was synthesized from the reaction of glycine and 2‧ hydroxy acetophenone and copper(II) acetate. The compounds were characterised by elemental analysis, spectral, magnetic and thermal studies. The density functional theory calculations were performed using LANL2DZ and 6-311 G(d, p) basis sets with B3LYP correlation functional to ascertain the stable electronic structure, HOMO-LUMO energy gap, chemical hardness and dipole moment of the mixed ligand complexes. A distorted square planar geometry has been conjectured for the complexes. Antibacterial activities of the ligand and its metal complexes have been tested against selected gram-positive and gram-negative strains and correlated with computational docking scores.

  9. Text Mining for Protein Docking.

    Directory of Open Access Journals (Sweden)

    Varsha D Badal

    2015-12-01

    Full Text Available The rapidly growing amount of publicly available information from biomedical research is readily accessible on the Internet, providing a powerful resource for predictive biomolecular modeling. The accumulated data on experimentally determined structures transformed structure prediction of proteins and protein complexes. Instead of exploring the enormous search space, predictive tools can simply proceed to the solution based on similarity to the existing, previously determined structures. A similar major paradigm shift is emerging due to the rapidly expanding amount of information, other than experimentally determined structures, which still can be used as constraints in biomolecular structure prediction. Automated text mining has been widely used in recreating protein interaction networks, as well as in detecting small ligand binding sites on protein structures. Combining and expanding these two well-developed areas of research, we applied the text mining to structural modeling of protein-protein complexes (protein docking. Protein docking can be significantly improved when constraints on the docking mode are available. We developed a procedure that retrieves published abstracts on a specific protein-protein interaction and extracts information relevant to docking. The procedure was assessed on protein complexes from Dockground (http://dockground.compbio.ku.edu. The results show that correct information on binding residues can be extracted for about half of the complexes. The amount of irrelevant information was reduced by conceptual analysis of a subset of the retrieved abstracts, based on the bag-of-words (features approach. Support Vector Machine models were trained and validated on the subset. The remaining abstracts were filtered by the best-performing models, which decreased the irrelevant information for ~ 25% complexes in the dataset. The extracted constraints were incorporated in the docking protocol and tested on the Dockground unbound

  10. Luminescent Behavior of Ru(II) Polypyridyl Morpholine Complexes, Synthesis, Characterization, DNA, Protein Binding, Sensor Effect of Ions/Solvents and Docking Studies.

    Science.gov (United States)

    Vuradi, Ravi Kumar; Putta, Venkat Reddy; Nancherla, Deepika; Sirasani, Satyanarayana

    2016-03-01

    New three ruthenium (II) polypyridyl complexes [Ru(phen)2mpip](2+)(1) {mpip = 2-(4-morpholinophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline}, (phen = 1,10-Phenanthrolene), [Ru(bpy)2mpip](2+)(2) (bpy = 2,2'bipyridyl), [Ru(dmb)2mpip](2+)(3) (dmb = 4, 4-dimethyl 2, 2'-bipyridine) have been synthesized and characterized by spectral studies IR, UV-vis, (1)H, (13)C-NMR, mass and elemental analysis. The binding properties of these three complexes towards calf-thymus DNA (CT-DNA) have been investigated by UV-Vis spectroscopy, different fluorescence methods and viscosity measurements, indicating that all the complexes bind to CT-DNA by means of intercalation, but with different binding affinities. Sensor effect of ions/solvents and BSA (Bovine Serum Albumin) binding studies of these complexes were also studied. Docking studies also reveals that complexes will bind in between base pairs (Intercalate) of DNA and gives information about the binding strength.

  11. Anticipatory postural adjustments to arm movement reveal complex control of paraspinal muscles in the thorax.

    Science.gov (United States)

    Lee, Linda-Joy; Coppieters, Michel W; Hodges, Paul W

    2009-02-01

    Anatomical and empirical data suggest that deep and superficial muscles may have different functions for thoracic spine control. This study investigated thoracic paraspinal muscle activity during anticipatory postural adjustments associated with arm movement. Electromyographic (EMG) recordings were made from the right deep (multifidus/rotatores) and superficial (longissimus) muscles at T5, T8, and T11 levels using fine-wire electrodes. Ten healthy participants performed fast unilateral and bilateral flexion and extension arm movements in response to a light. EMG amplitude was measured during 25ms epochs for 150ms before and 400ms after deltoid EMG onset. During arm flexion movements, multifidus and longissimus had two bursts of activity, one burst prior to deltoid and a late burst. With arm extension both muscles were active in a single burst after deltoid onset. There was differential activity with respect to direction of trunk rotation induced by arm movement. Right longissimus was most active with left arm movements and right multifidus was most active with right arm movements. All levels of the thorax responded similarly. We suggest that although thoracic multifidus and longissimus function similarly to control sagittal plane perturbations, these muscles are differentially active with rotational forces on the trunk.

  12. Side docking of the da Vinci robotic system for radical prostatectomy: advantages over traditional docking.

    Science.gov (United States)

    Cestari, Andrea; Ferrari, Matteo; Zanoni, Matteo; Sangalli, Mattia; Ghezzi, Massimo; Fabbri, Fabio; Sozzi, Francesco; Rigatti, Patrizio

    2015-09-01

    The standard low lithotomic position, used during robot-assisted radical prostatectomy (RARP), with prolonged positioning in stirrups together with steep Trendelenburg may expose the patient to neurapraxia phenomena of the lower limbs and can rarely be used in patients with problems of hip abduction. To overcome these hurdles, we evaluated the clinical benefits of "side docking" (SD) of the da Vinci(®) robotic system in comparison to "traditional docking" (TD). A cohort of 120 patients submitted to RARP were prospectively randomized into two groups by docking approach: SD with the patient supine with lower limbs slightly abducted on the operating table, and TD docking time, intraoperative number of collisions between the robotic arms and postoperative neurological problems in the lower limbs were noted. Descriptive statistics was used to analyze outcomes. Docking time was shorter for the SD group [SD: median 13 min (range 10-18); TD: median 21 min (range 15-34)]. None in the SD group and six of 60 patients (10%) in the TD group suffered from temporary (<30 days) unilateral neurological deficits of the lower limbs. In both groups no collisions between the robotic arms occurred. The SD approach is technically feasible. It does not cause collisions between the robotic arms, and is a reliable method for reducing the setup time of RARP. The supine position of the patient may prevent neurological complications of the lower limbs. Based on these results, SD has become the standard docking technique used by our department.

  13. Dinuclear manganese(II) complexes of hexaazamacrocycles bearing N-benzoylated pendant separated by aromatic spacers: Antibacterial, DNA interaction, cytotoxic and molecular docking studies.

    Science.gov (United States)

    Arthi, P; Shobana, S; Srinivasan, P; Prabhu, D; Arulvasu, C; Kalilur Rahiman, A

    2015-12-01

    Three new homodinuclear manganese(II) complexes of the type [Mn2L(1-3)(ClO4)(H2O)](ClO4)3 (1-3) have been synthesized via cyclocondensation of terephthalaldehyde with three different benzoylated pendants in the presence of manganese(II) perchlorate and characterized by spectroscopic methods. Cyclic voltammetric investigation of complexes (1-3) depict two quasi-reversible one electron reduction processes in the cathodic potential region (E(1)pc=-0.73 to-0.83 V, E(2)pc=-1.31 to -1.40 V) and two quasi-reversible one electron oxidation processes in the anodic potential region (E(1)pa=1.03 to 1.10 V, E(2)pa=1.69 to 1.77 V). Electronic absorption spectra of the complexes suggested tetrahedral geometry around the central metal ion. The observed low magnetic moment values (μeff, 5.60-5.68 B.M.) of the complexes indicate the presence of an antiferromagnetic spin-exchange interaction between two metal centers, which was also supported by the broad EPR signal. All the compounds were tested for antibacterial activity against Gram (-ve) and Gram (+ve) bacterial strains. The binding studies of complexes with CT-DNA suggested minor-groove mode of interaction. Molecular docking studies were carried out in order to find the binding affinity of complexes with DNA and protein EGFR Kinase. The complexes are stabilized by additional electrostatic and van der Waals interaction with the DNA, and support minor groove mode of binding. The cleavage activity of complexes on pBR322 plasmid DNA displays efficient activity through a mechanistic pathway involving hydroxyl radicals. The cytotoxicity of complexes 2 and 3 have been tested against human liver adenocarcinoma (HepG2) cell line. Nuclear-chromatin cleavage has also been observed with propidium iodide (PI) staining and alkaline single-cell gel electrophoresis (comet assay) techniques.

  14. Study of the interaction between two newly synthesized cyclometallated platinum (II) complexes and human serum albumin: Spectroscopic characterization and docking simulation

    Energy Technology Data Exchange (ETDEWEB)

    Yousefi, Reza, E-mail: ryousefi@shirazu.ac.ir [Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz (Iran, Islamic Republic of); Mohammadi, Roghayeh [Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz (Iran, Islamic Republic of); Taheri-Kafrani, Asghar [Department of Biotechnology, Faculty of Advanced Sciences and Technologies, University of Isfahan, Isfahan 81746-73441 (Iran, Islamic Republic of); Bagher Shahsavani, Mohammad [Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz (Iran, Islamic Republic of); Dadkhah Aseman, Marzieh; Masoud Nabavizadeh, S.; Rashidi, Mehdi [Department of Chemistry, College of Sciences, Shiraz University, Shiraz (Iran, Islamic Republic of); Poursasan, Najmeh; Moosavi-Movahedi, Ali-Akbar [Institute of Biochemistry and Biophysics (IBB), the University of Tehran, Tehran (Iran, Islamic Republic of)

    2015-03-15

    This study describes HSA binding properties of two cyclometalated platinum (II) complexes with non-leaving lipophilic ligands; deprotonated 2-phenylpyridine (ppy): C{sub 1} and deprotonated benzo [h]quinolone (bhq): C{sub 2}, using UV–vis, fluorescence and circular dichroism (CD) spectroscopy. The absorption spectra of HSA decreased in the presence of increasing concentration of these complexes, reflecting HSA structural alteration after drug's binding. Also the thermodynamic parameters (ΔG, ΔH and ΔS) that obtained from Trp fluorescence study revealed that the interaction between these complexes and HSA were spontaneous. In addition, C{sub 1} with flexible chemical structure indicated significantly higher fluorescence quenching and binding affinity to HSA than C{sub 2} which possesses a higher structural rigidity. The ANS fluorescence results also indicated that two Pt (II) complexes were competing for binding to the hydrophobic regions of HSA. Moreover, CD results demonstrated that C{sub 2} complex induced alteration of HSA conformation to more significant extent compared to C{sub 1}. The molecular docking results revealed the involvement of π–π stacking and hydrophobic interaction between these complexes and the protein. Overall, this study may highlight the significance of structural flexibility in designing of future anticancer Pt (II) complexes with improved binding affinity for HSA. - Highlights: • HSA is a general transport carrier for a wide variety of ligands such as metabolites and pharmaceutical drugs. • The HSA binding properties of two structurally related cyclometallated platinum (II) complexes (C{sub 1} and C{sub 2}) were studied. • The complexes can bind to HSA and induce structural alteration in this protein. • The thermodynamic parameters revealed that the interactions were spontaneous and mainly hydrophobic driven. • C{sub 1} with flexible chemical structure indicated a higher binding affinity for HSA than C{sub 2}.

  15. Energetic Mechanism of Cytochrome c-Cytochrome c Oxidase Electron Transfer Complex Formation under Turnover Conditions Revealed by Mutational Effects and Docking Simulation.

    Science.gov (United States)

    Sato, Wataru; Hitaoka, Seiji; Inoue, Kaoru; Imai, Mizue; Saio, Tomohide; Uchida, Takeshi; Shinzawa-Itoh, Kyoko; Yoshikawa, Shinya; Yoshizawa, Kazunari; Ishimori, Koichiro

    2016-07-15

    Based on the mutational effects on the steady-state kinetics of the electron transfer reaction and our NMR analysis of the interaction site (Sakamoto, K., Kamiya, M., Imai, M., Shinzawa-Itoh, K., Uchida, T., Kawano, K., Yoshikawa, S., and Ishimori, K. (2011) Proc. Natl. Acad. Sci. U.S.A. 108, 12271-12276), we determined the structure of the electron transfer complex between cytochrome c (Cyt c) and cytochrome c oxidase (CcO) under turnover conditions and energetically characterized the interactions essential for complex formation. The complex structures predicted by the protein docking simulation were computationally selected and validated by the experimental kinetic data for mutant Cyt c in the electron transfer reaction to CcO. The interaction analysis using the selected Cyt c-CcO complex structure revealed the electrostatic and hydrophobic contributions of each amino acid residue to the free energy required for complex formation. Several charged residues showed large unfavorable (desolvation) electrostatic interactions that were almost cancelled out by large favorable (Columbic) electrostatic interactions but resulted in the destabilization of the complex. The residual destabilizing free energy is compensated by the van der Waals interactions mediated by hydrophobic amino acid residues to give the stabilized complex. Thus, hydrophobic interactions are the primary factors that promote complex formation between Cyt c and CcO under turnover conditions, whereas the change in the electrostatic destabilization free energy provides the variance of the binding free energy in the mutants. The distribution of favorable and unfavorable electrostatic interactions in the interaction site determines the orientation of the binding of Cyt c on CcO.

  16. Synthesis, interactions, molecular structure, biological properties and molecular docking studies on Mn, Co, Zn complexes containing acetylacetone and pyridine ligands with DNA duplex.

    Science.gov (United States)

    Thamilarasan, V; Sengottuvelan, N; Stalin, N; Srinivasan, P; Chakkaravarthi, G

    2016-07-01

    Three metal complexes (1-3) of the type [Mn(acac)2(py)·H2O] (1), [Co(acac)2(py)·H2O] (2) and [Zn(acac)2(py)·H2O] (3), [Where acac=acetylacetone, py=pyridine] were synthesized and characterized by spectral (UV-vis, FT-IR, ESI-mass) analysis. The structure of complex 2 has been determined by single crystal X-ray diffraction studies and the configuration of ligand-coordinated to metal(II) ion was well described as distorted octahedral coordination geometry. The interaction of the complexes with CT-DNA has been explored by absorption, fluorescence, circular dichromism spectroscopy, viscosity measurements and molecular docking studies. The intrinsic binding constant Kb of complexes 1-3 with CT-DNA obtained from UV-vis absorption spectral studies were 2.1×10(4), 2.1×10(5) and 1.98×10(4)M(-1), respectively, which revealed that the complexes could interact with CT-DNA through groove binding. The results indicated that the complexes (1-3) were able to bind to DNA with different binding affinity, in the order: 2>1>3. The interaction of the compounds with bovine serum albumins were also investigated using fluorescence methods and the gel electrophoresis assay demonstrates weak cleavage ability of the pBR322 plasmid DNA in the presence of the metal complexes (1-3) with various activators. Further, the in vitro cytotoxic effect of the complexes were examined on cancerous cell line, with human breast cancer cells MCF-7.

  17. Synthesis and luminescence properties of lanthanide complexes with a new tripodal ligand featuring N-thenylsalicylamide arms.

    Science.gov (United States)

    Song, Xue-Qin; Zheng, Qing-Fang; Wang, Li; Liu, Wei-Sheng

    2012-01-01

    To explore the relationship between the structure of the ligands and the luminescent properties of the lanthanide complexes, luminescent lanthanide complexes of a new tripodal ligand, featuring N-thenylsalicylamide arms, were synthesized and characterized by elemental analysis, IR and TGA measurements. Photophysical properties of the complexes were studied by means of UV - visible absorption and steady-state luminescence spectroscopy. The results of UV - vis spectra indicate that metal binding does not disturb the electronic structure of the ligand. Excited-state luminescence lifetimes and quantum yields of the complexes were determined. The photoluminescence analysis suggested that there is an efficient ligand - Ln(III) energy transfer for the Tb(III) complex, and the ligand is an efficient 'antenna' for Tb(III). From a more general perspective, the results demonstrated the potential application of the lanthanide complex as luminescent materials in material chemistry.

  18. The HADDOCK web server for data-driven biomolecular docking

    NARCIS (Netherlands)

    de Vries, S.J.; van Dijk, M.; Bonvin, A.M.J.J.

    2010-01-01

    Computational docking is the prediction or modeling of the three-dimensional structure of a biomolecular complex, starting from the structures of the individual molecules in their free, unbound form. HADDOC K is a popular docking program that takes a datadriven approach to docking, with support for

  19. Field guide to the Mesozoic accretionary complex along Turnagain Arm and Kachemak Bay, south-central Alaska

    Science.gov (United States)

    Bradley, Dwight C.; Kusky, Timothy M.; Karl, Susan M.; Haeussler, Peter J.

    1997-01-01

    Turnagain Arm, just east of Anchorage, provides a readily accessible, world-class cross section through a Mesozoic accretionary wedge. Nearly continuous exposures along the Seward Highway, the Alaska Railroad, and the shoreline of Turnagain Arm display the two main constituent units of the Chugach terrane: the McHugh Complex and Valdez Group. In this paper we describe seven bedrock geology stops along Turnagain Arm, and two others in the Chugach Mountains just to the north (Stops 1-7 and 9), which will be visited as part of the May, 1997 field trip of the Alaska Geological Society. Outcrops along Turnagain Arm have already been described in two excellent guidebook articles (Clark, 1981; Winkler and others 1984), both of which remain as useful and valid today as when first published. Since the early 1980's, studies along Turnagain Arm have addressed radiolarian ages of chert and conodont ages of limestone in the McHugh Complex (Nelson and others, 1986, 1987); geochemistry of basalt in the McHugh Complex (Nelson and Blome, 1991); post-accretion brittle faulting (Bradley and Kusky, 1990; Kusky and others, 1997); and the age and tectonic setting of gold mineralization (Haeussler and others, 1995). Highlights of these newer findings will described both in the text below, and in the stop descriptions.Superb exposures along the southeastern shore of Kachemak Bay show several other features of the McHugh Complex that are either absent or less convincing along Turnagain Arm. While none of these outcrops can be reached via the main road network, they are still reasonably accessible - all are within an hour by motorboat from Homer, seas permitting. Here, we describe seven outcrops along the shore of Kachemak Bay that we studied between 1989 and 1993 during geologic mapping of the Seldovia 1:250,000- scale quadrangle. These outcrops (Stops 61-67) will not be part of the 1997 itinerary, but are included here tor the benefit of those who may wish to visit them later.

  20. Exploring the selectivity of auto-inducer complex with LuxR using molecular docking, mutational studies and molecular dynamics simulations

    Science.gov (United States)

    Rajamanikandan, Sundaraj; Srinivasan, Pappu

    2017-03-01

    Bacteria communicate with one another using extracellular signaling molecules called auto-inducers (AHLs), a process termed as quorum sensing. The quorum sensing process allows bacteria to regulate various physiological activities. In this regard, quorum sensing master regulator LuxR from Vibrio harveyi represents an attractive therapeutic target for the development of novel anti-quorum sensing agents. Eventhough the binding of AHL complex with LuxR is evidenced in earlier reports, but their mode of binding is not clearly determined. Therefore, in the present work, molecular docking, in silico mutational studies, molecular dynamics simulations and free energy calculations were performed to understand the selectivity of AHL into the binding site of LuxR. The results revealed that Asn133 and Gln137 residues play a crucial role in recognizing AHL more effectively into the binding site of LuxR with good binding free energy. In addition to that, the carbonyl group presents in the lactone ring and amide group of AHL plays a vital role in the formation of hydrogen bond interactions with the protein. Further, structure based virtual screening was performed using ChemBridge database to screen potent lead molecules against LuxR. 4-benzyl-2-pyrrolidinone and N-[2(1-cyclohexen-1-yl) enthyl]-N'(2-ethoxyphenyl) were selected based on dock score, binding affinity and mode of interactions with the receptor. Furthermore, binding free energy, density functional theory and ADME prediction were performed to rank the lead molecules. Thus, the identified lead molecules can be used for the development of anti-quorum sensing drugs.

  1. Synthesis, spectroscopic properties, molecular docking, anti-colon cancer and anti-microbial studies of some novel metal complexes for 2-amino-4-phenylthiazole derivative

    Science.gov (United States)

    Al-Harbi, Sami A.; Bashandy, Mahmoud S.; Al-Saidi, Hammed M.; Emara, Adel A. A.; Mousa, Tarek A. A.

    2015-06-01

    This article describes the synthesis of novel bidentate Schiff base (H2L) from condensation of 2-amino-4-phenylthiazole (APT) with 4,6-diacetylresorcinol (DAR) in the molar ratio 2:1. We studied interaction of ligand (H2L) with transition metal ions such as Cr(III), Fe(III), Cu(II), Zn(II) and Cd(II). The ligand (H2L) has two bidentate sets of (N-O) units which can coordinate with two metal ions to afford novel binuclear metal complexes. The directions of coordinate bonds are from nitrogen atoms of azomethine groups and oxygen atoms of the phenolic groups. Structures of the newly synthesized complexes were confirmed by elemental analysis, IR, UV, 1H NMR, ESR, TGA and mass spectral data. All of the newly synthesized complexes were evaluated for their antibacterial and anti-fungal activities. They were also evaluated for their in vitro anticancer activity against human colon carcinoma cells (HCT-116) and mammalian cells of African green monkey kidney (VERO). The Cu(II) complex with selectivity index (S.I.) = 21.26 exhibited better activity than methotrexate (MTX) as a reference drug with S.I. value = 13.30, while Zn(II) complex with S.I. value = 10.24 was found to be nearly as active as MTX. Molecular docking studies further helped in understanding the mode of action of the compounds through their various interactions with active sites of dihydrofolate reductase (DHFR) enzyme. The observed activity of Fe(III) and Cu(II) complexes gave rise to the conclusion that they might exert their action through inhibition of the DHFR enzyme.

  2. Protein docking prediction using predicted protein-protein interface

    Directory of Open Access Journals (Sweden)

    Li Bin

    2012-01-01

    Full Text Available Abstract Background Many important cellular processes are carried out by protein complexes. To provide physical pictures of interacting proteins, many computational protein-protein prediction methods have been developed in the past. However, it is still difficult to identify the correct docking complex structure within top ranks among alternative conformations. Results We present a novel protein docking algorithm that utilizes imperfect protein-protein binding interface prediction for guiding protein docking. Since the accuracy of protein binding site prediction varies depending on cases, the challenge is to develop a method which does not deteriorate but improves docking results by using a binding site prediction which may not be 100% accurate. The algorithm, named PI-LZerD (using Predicted Interface with Local 3D Zernike descriptor-based Docking algorithm, is based on a pair wise protein docking prediction algorithm, LZerD, which we have developed earlier. PI-LZerD starts from performing docking prediction using the provided protein-protein binding interface prediction as constraints, which is followed by the second round of docking with updated docking interface information to further improve docking conformation. Benchmark results on bound and unbound cases show that PI-LZerD consistently improves the docking prediction accuracy as compared with docking without using binding site prediction or using the binding site prediction as post-filtering. Conclusion We have developed PI-LZerD, a pairwise docking algorithm, which uses imperfect protein-protein binding interface prediction to improve docking accuracy. PI-LZerD consistently showed better prediction accuracy over alternative methods in the series of benchmark experiments including docking using actual docking interface site predictions as well as unbound docking cases.

  3. Fully automated flexible docking of ligands into flexible synthetic receptors using forward and inverse docking strategies.

    Science.gov (United States)

    Kämper, Andreas; Apostolakis, Joannis; Rarey, Matthias; Marian, Christel M; Lengauer, Thomas

    2006-01-01

    The prediction of the structure of host-guest complexes is one of the most challenging problems in supramolecular chemistry. Usual procedures for docking of ligands into receptors do not take full conformational freedom of the host molecule into account. We describe and apply a new docking approach which performs a conformational sampling of the host and then sequentially docks the ligand into all receptor conformers using the incremental construction technique of the FlexX software platform. The applicability of this approach is validated on a set of host-guest complexes with known crystal structure. Moreover, we demonstrate that due to the interchangeability of the roles of host and guest, the docking process can be inverted. In this inverse docking mode, the receptor molecule is docked around its ligand. For all investigated test cases, the predicted structures are in good agreement with the experiment for both normal (forward) and inverse docking. Since the ligand is often smaller than the receptor and, thus, its conformational space is more restricted, the inverse docking approach leads in most cases to considerable speed-up. By having the choice between two alternative docking directions, the application range of the method is significantly extended. Finally, an important result of this study is the suitability of the simple energy function used here for structure prediction of complexes in organic media.

  4. Extracellular signal-regulated kinase 2 (ERK2) phosphorylation sites and docking domain on the nuclear pore complex protein Tpr cooperatively regulate ERK2-Tpr interaction.

    Science.gov (United States)

    Vomastek, Tomás; Iwanicki, Marcin P; Burack, W Richard; Tiwari, Divya; Kumar, Devanand; Parsons, J Thomas; Weber, Michael J; Nandicoori, Vinay Kumar

    2008-11-01

    Identifying direct substrates of mitogen-activated protein kinases (MAPKs) and understanding how those substrates are selected is central to understanding how these ubiquitously activated enzymes generate diverse biological responses. In previous work, we identified several new candidate substrates for the MAPK ERK2 (extracellular signal-regulated kinase 2), including the nuclear pore complex protein Tpr (translocated promoter region). In this report, we identify sites on Tpr for ERK2 phosphorylation and binding and demonstrate their functional interaction. ERK2 phosphorylation and dimerization are necessary for ERK2-Tpr binding, and this occurs through a DEF (docking site for ERK2, FXF) domain on Tpr. Surprisingly, the DEF domain and the phosphorylation sites displayed positive cooperativity to promote ERK2 binding to Tpr, in contrast to substrates where phosphorylation reduces binding. Ectopic expression or depletion of Tpr resulted in decreased movement of activated ERK2 from the cytoplasm to the nucleus, implying a role for Tpr in ERK2 translocation. Collectively, the data provide direct evidence that a component of the nuclear pore complex is a bona fide substrate of ERK2 in vivo and that activated ERK2 stably associates with this substrate after phosphorylation, where it could play a continuing role in nuclear pore function. We propose that Tpr is both a substrate and a scaffold for activated ERKs.

  5. A general approach for developing system-specific functions to score protein-ligand docked complexes using support vector inductive logic programming.

    Science.gov (United States)

    Amini, Ata; Shrimpton, Paul J; Muggleton, Stephen H; Sternberg, Michael J E

    2007-12-01

    Despite the increased recent use of protein-ligand and protein-protein docking in the drug discovery process due to the increases in computational power, the difficulty of accurately ranking the binding affinities of a series of ligands or a series of proteins docked to a protein receptor remains largely unsolved. This problem is of major concern in lead optimization procedures and has lead to the development of scoring functions tailored to rank the binding affinities of a series of ligands to a specific system. However, such methods can take a long time to develop and their transferability to other systems remains open to question. Here we demonstrate that given a suitable amount of background information a new approach using support vector inductive logic programming (SVILP) can be used to produce system-specific scoring functions. Inductive logic programming (ILP) learns logic-based rules for a given dataset that can be used to describe properties of each member of the set in a qualitative manner. By combining ILP with support vector machine regression, a quantitative set of rules can be obtained. SVILP has previously been used in a biological context to examine datasets containing a series of singular molecular structures and properties. Here we describe the use of SVILP to produce binding affinity predictions of a series of ligands to a particular protein. We also for the first time examine the applicability of SVILP techniques to datasets consisting of protein-ligand complexes. Our results show that SVILP performs comparably with other state-of-the-art methods on five protein-ligand systems as judged by similar cross-validated squares of their correlation coefficients. A McNemar test comparing SVILP to CoMFA and CoMSIA across the five systems indicates our method to be significantly better on one occasion. The ability to graphically display and understand the SVILP-produced rules is demonstrated and this feature of ILP can be used to derive hypothesis for

  6. Synthesis, characterization, DNA interactions, DNA cleavage, radical scavenging activity, antibacterial, anti-proliferative and docking studies of new transition metal complexes.

    Science.gov (United States)

    Chennam, Kishan Prasad; Ravi, Mudavath; Ushaiah, B; Srinu, V; Eslavath, Ravi Kumar; Devi, Ch Sarala

    2016-01-01

    The compound N-(2-hydroxybenzylidene)-1-ethyl-1, 4-dihydro-7-methyl-4-oxo-1, 8 naphthyridine-3-carbohydrazide (LH) and its Cu (II), Co (II) and Zn (II) complexes were synthesized and characterized. The absorption spectral titrations and competitive DNA binding studies depicted those complexes of title compound bind to CT-DNA through intercalation. Interestingly [Cu (II)-(L2)] showed relatively high binding constant value (6.61 x 10(5) M(-1)) compared to [Co (II)-(L2)] (4.378× 10(5) M(-1)) and [Zn (II)-(L2)] (3.1x10(5) M(-1)). Ligand and its complexes were also examined for DNA nuclease activity against pBR-322 plasmid DNA, which showed that [Cu (II)-(L2)] had the best hydrolytic cleavage property displaying prominent double-strand DNA cleavage. In addition, antioxidant activities of the ligand and its metal complexes investigated through scavenging effects for DPPH radical in- vitro, indicated their potentiality as good antioxidants. The in vitro anti-bacterial study inferred the better anti-bacterial activity of [Cu (II)-(L2)] and this was also correlated theoretically by employing docking studies wherein [Cu (II)-(L2)] displayed good Gold score and Chem score. Finally the in vitro anti- proliferative activity of studied compounds was tested against HeLa and MCF-7 cell lines. Interestingly [Cu (II)-(L2)] displayed lower IC50 value and lower percentage of viability in both HeLa and MCF-7 cell lines.

  7. Pendant-armed Unsymmetrical Aza-macrocycles: Syntheses,Coordination Behavior and Crystal Structure of a Dinuclear Cadmium Complex

    Institute of Scientific and Technical Information of China (English)

    TAO,Jing-Chao(陶京朝); LIAO,Xin-Cheng(廖新成); WANG,Xing-Wang(王兴旺); DU,Chen-Xia(杜晨霞)

    2002-01-01

    Two nsymmetrical tetradentate aza-macrocycles with side arms attached to the N3sp atoms, L1 and L2, as well as their complexes with different metal cations were synthesized and characterized by EA, UV, IR, 1H NMR and MS spectra. Both the two ligands can efficiently transport alkali and transition metal cations across an organic membrane with high selectivity ratio. The structure of a dinuclear Cd(Ⅱ)complex [L1@(CdCl2)2] was elucdated by X-ray crystallography and was solved by the heavy-atom method to afinal R value of 0.029 for 3084reflections with |F| >3σ(I). In the exo-structore of the dinuclear complex each cadmium atom is five-coordinated, bonding to three N atoms and two chlorine atoms.

  8. Pendant—armed Unsymmetrical Aza—macrocycles:Syntheses,Coordination Behavior and Crystal Structure of a Dinuclear Cadmium Complex

    Institute of Scientific and Technical Information of China (English)

    陶京朝; 廖新成; 等

    2002-01-01

    Two unsymmetridcal tetradentate aza-macrocycles with side arms attached to whte Nsp3 atoms ,L1 and L2 ,as well as their complexes with different metal cations were synthesized and characterized by EA,UV IR ,1H NMR and MS spectra ,Both the two ligands can efficiently transport alkai and transition metal cations across an organic membrane with high selectivity ratio.The structure of a dinuclear Cd(Ⅱ) complex [L1.(CdCl2)2] was elucidated by X-ray crystallography and was solved by the heavy-atom method to a final R value of 0.029 for 3084 reflections with |F|>3σ(I), In the exo-structure of the dinuclear complex each cadmium atom is five-coordinated,bonding to three N atoms and two chlorine atoms.

  9. Protein-protein docking with F(2Dock 2.0 and GB-rerank.

    Directory of Open Access Journals (Sweden)

    Rezaul Chowdhury

    Full Text Available MOTIVATION: Computational simulation of protein-protein docking can expedite the process of molecular modeling and drug discovery. This paper reports on our new F(2 Dock protocol which improves the state of the art in initial stage rigid body exhaustive docking search, scoring and ranking by introducing improvements in the shape-complementarity and electrostatics affinity functions, a new knowledge-based interface propensity term with FFT formulation, a set of novel knowledge-based filters and finally a solvation energy (GBSA based reranking technique. Our algorithms are based on highly efficient data structures including the dynamic packing grids and octrees which significantly speed up the computations and also provide guaranteed bounds on approximation error. RESULTS: The improved affinity functions show superior performance compared to their traditional counterparts in finding correct docking poses at higher ranks. We found that the new filters and the GBSA based reranking individually and in combination significantly improve the accuracy of docking predictions with only minor increase in computation time. We compared F(2 Dock 2.0 with ZDock 3.0.2 and found improvements over it, specifically among 176 complexes in ZLab Benchmark 4.0, F(2 Dock 2.0 finds a near-native solution as the top prediction for 22 complexes; where ZDock 3.0.2 does so for 13 complexes. F(2 Dock 2.0 finds a near-native solution within the top 1000 predictions for 106 complexes as opposed to 104 complexes for ZDock 3.0.2. However, there are 17 and 15 complexes where F(2 Dock 2.0 finds a solution but ZDock 3.0.2 does not and vice versa; which indicates that the two docking protocols can also complement each other. AVAILABILITY: The docking protocol has been implemented as a server with a graphical client (TexMol which allows the user to manage multiple docking jobs, and visualize the docked poses and interfaces. Both the server and client are available for download. Server

  10. SwissDock, a protein-small molecule docking web service based on EADock DSS.

    Science.gov (United States)

    Grosdidier, Aurélien; Zoete, Vincent; Michielin, Olivier

    2011-07-01

    Most life science processes involve, at the atomic scale, recognition between two molecules. The prediction of such interactions at the molecular level, by so-called docking software, is a non-trivial task. Docking programs have a wide range of applications ranging from protein engineering to drug design. This article presents SwissDock, a web server dedicated to the docking of small molecules on target proteins. It is based on the EADock DSS engine, combined with setup scripts for curating common problems and for preparing both the target protein and the ligand input files. An efficient Ajax/HTML interface was designed and implemented so that scientists can easily submit dockings and retrieve the predicted complexes. For automated docking tasks, a programmatic SOAP interface has been set up and template programs can be downloaded in Perl, Python and PHP. The web site also provides an access to a database of manually curated complexes, based on the Ligand Protein Database. A wiki and a forum are available to the community to promote interactions between users. The SwissDock web site is available online at http://www.swissdock.ch. We believe it constitutes a step toward generalizing the use of docking tools beyond the traditional molecular modeling community.

  11. Lock-arm supramolecular ordering: a molecular construction set for cocrystallizing organic charge transfer complexes.

    Science.gov (United States)

    Blackburn, Anthea K; Sue, Andrew C-H; Shveyd, Alexander K; Cao, Dennis; Tayi, Alok; Narayanan, Ashwin; Rolczynski, Brian S; Szarko, Jodi M; Bozdemir, Ozgur A; Wakabayashi, Rie; Lehrman, Jessica A; Kahr, Bart; Chen, Lin X; Nassar, Majed S; Stupp, Samuel I; Stoddart, J Fraser

    2014-12-10

    Organic charge transfer cocrystals are inexpensive, modular, and solution-processable materials that are able, in some instances, to exhibit properties such as optical nonlinearity, (semi)conductivity, ferroelectricity, and magnetism. Although the properties of these cocrystals have been investigated for decades, the principal challenge that researchers face currently is to devise an efficient approach which allows for the growth of high-quality crystalline materials, in anticipation of a host of different technological applications. The research reported here introduces an innovative design, termed LASO-lock-arm supramolecular ordering-in the form of a modular approach for the development of responsive organic cocrystals. The strategy relies on the use of aromatic electronic donor and acceptor building blocks, carrying complementary rigid and flexible arms, capable of forming hydrogen bonds to amplify the cocrystallization processes. The cooperativity of charge transfer and hydrogen-bonding interactions between the building blocks leads to binary cocrystals that have alternating donors and acceptors extending in one and two dimensions sustained by an intricate network of hydrogen bonds. A variety of air-stable, mechanically robust, centimeter-long, organic charge transfer cocrystals have been grown by liquid-liquid diffusion under ambient conditions inside 72 h. These cocrystals are of considerable interest because of their remarkable size and stability and the promise they hold when it comes to fabricating the next generation of innovative electronic and photonic devices.

  12. International Docking Standardization NASA

    Science.gov (United States)

    Donahoe, Stanley; Lewis, J.; Carroll, M.; Le, T.

    2009-01-01

    This slide presentation reviews the different types of docking types. The objective is the pressurized vehicle connection and crew transfer. Androgynous Docking is defined as the joining or coming together of two free flying space vehicles with alike interfaces. Androgynous mating allows for collaboration between any two vehicles. The subsytems of an androgynous mating system are reviewed, including: Hard docking subsystems: latch system, tunnel housing, alignment system and seal.

  13. A Chlamydomonas Homologue of the Putative Murine t Complex Distorter Tctex-2 Is an Outer Arm Dynein Light Chain

    Science.gov (United States)

    Patel-King, Ramila S.; Benashski, Sharon E.; Harrison, Alistair; King, Stephen M.

    1997-01-01

    Molecular analysis of a 19,000-Mr protein from the Chlamydomonas flagellum reveals that it is homologous to the t complex–encoded protein Tctex-2, which is a candidate for one of the distorter products that cause the extreme transmission ratio distortion (meiotic drive) of the murine t complex. The 19,000-Mr protein is extracted from the axoneme with 0.6 M NaCl and comigrates with the outer dynein arm in sucrose density gradients. This protein also is specifically missing in axonemes prepared from a mutant that does not assemble the outer arm. These data raise the possibility that Tctex-2 is a sperm flagellar dynein component. Combined with the recent identification of Tctex-1 (another distorter candidate) as a light chain of cytoplasmic dynein, these results lead to a biochemical model for how differential defects in spermiogenesis that result in the phenomenon of meiotic drive might be generated in wild-type vs t-bearing sperm. PMID:9166408

  14. Transport of the outer dynein arm complex to cilia requires a cytoplasmic protein Lrrc6.

    Science.gov (United States)

    Inaba, Yasuko; Shinohara, Kyosuke; Botilde, Yanick; Nabeshima, Ryo; Takaoka, Katsuyoshi; Ajima, Rieko; Lamri, Lynda; Takeda, Hiroyuki; Saga, Yumiko; Nakamura, Tetsuya; Hamada, Hiroshi

    2016-07-01

    Lrrc6 encodes a cytoplasmic protein that is expressed specifically in cells with motile cilia including the node, trachea and testes of the mice. A mutation of Lrrc6 has been identified in human patients with primary ciliary dyskinesia (PCD). Mutant mice lacking Lrrc6 show typical PCD defects such as hydrocephalus and laterality defects. We found that in the absence of Lrrc6, the morphology of motile cilia remained normal, but their motility was completely lost. The 9 + 2 arrangement of microtubules remained normal in Lrrc6(-/-) mice, but the outer dynein arms (ODAs), the structures essential for the ciliary beating, were absent from the cilia. In the absence of Lrrc6, ODA proteins such as DNAH5, DNAH9 and IC2, which are assembled in the cytoplasm and transported to the ciliary axoneme, remained in the cytoplasm and were not transported to the ciliary axoneme. The IC2-IC1 interaction, which is the first step of ODA assembly, was normal in Lrrc6(-/-) mice testes. Our results suggest that ODA proteins may be transported from the cytoplasm to the cilia by an Lrrc6-dependent mechanism.

  15. Ruthenium(II) pincer complexes with oxazoline arms for efficient transfer hydrogenation reactions

    KAUST Repository

    Chen, Tao

    2012-08-01

    Well-defined P NN CN pincer ruthenium complexes bearing both strong phosphine and weak oxazoline donors were developed. These easily accessible complexes exhibit significantly better catalytic activity in transfer hydrogenation of ketones compared to their PN 3P analogs. These reactions proceed under mild and base-free conditions via protonation- deprotonation of the \\'NH\\' group in the aromatization-dearomatization process. © 2012 Elsevier Ltd. All rights reserved.

  16. VORFFIP-Driven Dock: V-D2OCK, a Fast and Accurate Protein Docking Strategy

    Science.gov (United States)

    Segura, Joan; Marín-López, Manuel Alejandro; Jones, Pamela F.; Oliva, Baldo; Fernandez-Fuentes, Narcis

    2015-01-01

    The experimental determination of the structure of protein complexes cannot keep pace with the generation of interactomic data, hence resulting in an ever-expanding gap. As the structural details of protein complexes are central to a full understanding of the function and dynamics of the cell machinery, alternative strategies are needed to circumvent the bottleneck in structure determination. Computational protein docking is a valid and valuable approach to model the structure of protein complexes. In this work, we describe a novel computational strategy to predict the structure of protein complexes based on data-driven docking: VORFFIP-driven dock (V-D2OCK). This new approach makes use of our newly described method to predict functional sites in protein structures, VORFFIP, to define the region to be sampled during docking and structural clustering to reduce the number of models to be examined by users. V-D2OCK has been benchmarked using a validated and diverse set of protein complexes and compared to a state-of-art docking method. The speed and accuracy compared to contemporary tools justifies the potential use of VD2OCK for high-throughput, genome-wide, protein docking. Finally, we have developed a web interface that allows users to browser and visualize V-D2OCK predictions from the convenience of their web-browsers. PMID:25763838

  17. VORFFIP-driven dock: V-D2OCK, a fast and accurate protein docking strategy.

    Directory of Open Access Journals (Sweden)

    Joan Segura

    Full Text Available The experimental determination of the structure of protein complexes cannot keep pace with the generation of interactomic data, hence resulting in an ever-expanding gap. As the structural details of protein complexes are central to a full understanding of the function and dynamics of the cell machinery, alternative strategies are needed to circumvent the bottleneck in structure determination. Computational protein docking is a valid and valuable approach to model the structure of protein complexes. In this work, we describe a novel computational strategy to predict the structure of protein complexes based on data-driven docking: VORFFIP-driven dock (V-D2OCK. This new approach makes use of our newly described method to predict functional sites in protein structures, VORFFIP, to define the region to be sampled during docking and structural clustering to reduce the number of models to be examined by users. V-D2OCK has been benchmarked using a validated and diverse set of protein complexes and compared to a state-of-art docking method. The speed and accuracy compared to contemporary tools justifies the potential use of VD2OCK for high-throughput, genome-wide, protein docking. Finally, we have developed a web interface that allows users to browser and visualize V-D2OCK predictions from the convenience of their web-browsers.

  18. Enantiomeric in vitro DNA binding, pBR322 DNA cleavage and molecular docking studies of chiral L- and D-ternary copper(II) complexes of histidine and picolinic acid.

    Science.gov (United States)

    Parveen, Shazia; Arjmand, Farukh; Ahmad, Iqbal

    2014-01-05

    Novel chiral ternary Cu(II) and Ni(II) complexes of l/d-histidine and picolinic acid, 1 and 2(a and b) were synthesized and characterized by elemental analysis, molar conductance and spectroscopic data (IR, NMR, EPR, UV-vis). In vitro DNA binding profile of both Cu(II) and Ni(II) complexes have been investigated by UV-vis titrations, while fluorescence spectroscopy, circular dichroism and viscosity measurements were carried out for Cu(II) complexes 1(a and b). Both the enantiomers of 1 and 2(a and b) bind to CT DNA via electrostatic interactions and the intrinsic binding constant, Kb values for complexes 1 and 2(a and b) were found to be 5.6×10(4), 9.8×10(3), 8.2×10(3) and 6.7×10(3)M(-1), respectively suggesting greater binding propensity of l-form of Cu(II) complex 1a. The DNA cleavage activity of complexes 1(a and b), investigated by agarose gel electrophoresis suggested an oxidative pathway for DNA cleavage. Further, the molecular docking studies of complexes 1(a and b) were carried out with B-DNA revealing that the complexes bind to the adenine-thymine residues in the minor groove of the DNA. The resulting binding energies of docked metal complexes 1(a and b) were found to be -265.1 and -218.9KJmol(-1), respectively. Furthermore, enantiomeric complexes 1 and 2(a and b) were screened for in vitro antimicrobial activity.

  19. Dockomatic - automated ligand creation and docking

    Directory of Open Access Journals (Sweden)

    Hampikian Greg

    2010-11-01

    Full Text Available Abstract Background The application of computational modeling to rationally design drugs and characterize macro biomolecular receptors has proven increasingly useful due to the accessibility of computing clusters and clouds. AutoDock is a well-known and powerful software program used to model ligand to receptor binding interactions. In its current version, AutoDock requires significant amounts of user time to setup and run jobs, and collect results. This paper presents DockoMatic, a user friendly Graphical User Interface (GUI application that eases and automates the creation and management of AutoDock jobs for high throughput screening of ligand to receptor interactions. Results DockoMatic allows the user to invoke and manage AutoDock jobs on a single computer or cluster, including jobs for evaluating secondary ligand interactions. It also automates the process of collecting, summarizing, and viewing results. In addition, DockoMatic automates creation of peptide ligand .pdb files from strings of single-letter amino acid abbreviations. Conclusions DockoMatic significantly reduces the complexity of managing multiple AutoDock jobs by facilitating ligand and AutoDock job creation and management.

  20. Udock, the interactive docking entertainment system.

    Science.gov (United States)

    Levieux, Guillaume; Tiger, Guillaume; Mader, Stéphanie; Zagury, Jean-François; Natkin, Stéphane; Montes, Matthieu

    2014-01-01

    Protein-protein interactions play a crucial role in biological processes. Protein docking calculations' goal is to predict, given two proteins of known structures, the associate conformation of the corresponding complex. Here, we present a new interactive protein docking system, Udock, that makes use of users' cognitive capabilities added up. In Udock, the users tackle simplified representations of protein structures and explore protein-protein interfaces' conformational space using a gamified interactive docking system with on the fly scoring. We assumed that if given appropriate tools, a naïve user's cognitive capabilities could provide relevant data for (1) the prediction of correct interfaces in binary protein complexes and (2) the identification of the experimental partner in interaction among a set of decoys. To explore this approach experimentally, we conducted a preliminary two week long playtest where the registered users could perform a cross-docking on a dataset comprising 4 binary protein complexes. The users explored almost all the surface of the proteins that were available in the dataset but favored certain regions that seemed more attractive as potential docking spots. These favored regions were located inside or nearby the experimental binding interface for 5 out of the 8 proteins in the dataset. For most of them, the best scores were obtained with the experimental partner. The alpha version of Udock is freely accessible at http://udock.fr.

  1. InterEvDock: a docking server to predict the structure of protein-protein interactions using evolutionary information.

    Science.gov (United States)

    Yu, Jinchao; Vavrusa, Marek; Andreani, Jessica; Rey, Julien; Tufféry, Pierre; Guerois, Raphaël

    2016-07-01

    The structural modeling of protein-protein interactions is key in understanding how cell machineries cross-talk with each other. Molecular docking simulations provide efficient means to explore how two unbound protein structures interact. InterEvDock is a server for protein docking based on a free rigid-body docking strategy. A systematic rigid-body docking search is performed using the FRODOCK program and the resulting models are re-scored with InterEvScore and SOAP-PP statistical potentials. The InterEvScore potential was specifically designed to integrate co-evolutionary information in the docking process. InterEvDock server is thus particularly well suited in case homologous sequences are available for both binding partners. The server returns 10 structures of the most likely consensus models together with 10 predicted residues most likely involved in the interface. In 91% of all complexes tested in the benchmark, at least one residue out of the 10 predicted is involved in the interface, providing useful guidelines for mutagenesis. InterEvDock is able to identify a correct model among the top10 models for 49% of the rigid-body cases with evolutionary information, making it a unique and efficient tool to explore structural interactomes under an evolutionary perspective. The InterEvDock web interface is available at http://bioserv.rpbs.univ-paris-diderot.fr/services/InterEvDock/.

  2. Synthesis, structural studies, and oxidation catalysis of the late-first-row-transition-metal complexes of a 2-pyridylmethyl pendant-armed ethylene cross-bridged cyclam.

    Science.gov (United States)

    Jones, Donald G; Wilson, Kevin R; Cannon-Smith, Desiray J; Shircliff, Anthony D; Zhang, Zhan; Chen, Zhuqi; Prior, Timothy J; Yin, Guochuan; Hubin, Timothy J

    2015-03-02

    The first 2-pyridylmethyl pendant-armed ethylene cross-bridged cyclam ligand has been synthesized and successfully complexed to Mn(2+), Fe(2+), Co(2+), Ni(2+), Cu(2+), and Zn(2+) cations. X-ray crystal structures were obtained for all six complexes and demonstrate pentadentate binding of the ligand with the requisite cis-V configuration of the cross-bridged cyclam ring in all cases, leaving a potential labile binding site cis to the pyridine donor for interaction of the complex with oxidants and/or substrates. The electronic properties of the complexes were evaluated using solid-state magnetic moment determination and acetonitrile solution electronic spectroscopy, which both agree with the crystal structure determination of high-spin divalent metal complexes in all cases. Cyclic voltammetry in acetonitrile revealed reversible redox processes in all but the Ni(2+) complex, suggesting that catalytic reactivity involving electron-transfer processes is possible for complexes of this ligand. Kinetic studies of the dissociation of the ligand from the copper(II) complex under strongly acidic conditions and elevated temperatures revealed that the pyridine pendant arm actually destabilizes the complex compared to the parent cross-bridged cyclam complex. Screening for oxidation catalysis using hydrogen peroxide as the terminal oxidant for the most biologically relevant Mn(2+), Fe(2+), and Cu(2+) complexes identified the Mn(2+) complex as a potential mild oxidation catalyst worthy of continued development.

  3. Protein Alpha Shape (PAS) Dock: A new gaussian-based score function suitable for docking in homology modelled protein structures

    Science.gov (United States)

    Tøndel, Kristin; Anderssen, Endre; Drabløs, Finn

    2006-03-01

    Protein Alpha Shape (PAS) Dock is a new empirical score function suitable for virtual library screening using homology modelled protein structures. Here, the score function is used in combination with the geometry search method Tabu search. A description of the protein binding site is generated using gaussian property fields like in Protein Alpha Shape Similarity Analysis (PASSA). Gaussian property fields are also used to describe the ligand properties. The overlap between the receptor and ligand hydrophilicity and lipophilicity fields is maximised, while minimising steric clashes. Gaussian functions introduce a smoothing of the property fields. This makes the score function robust against small structural variations, and therefore suitable for use with homology models. This also makes it less critical to include protein flexibility in the docking calculations. We use a fast and simplified version of the score function in the geometry search, while a more detailed version is used for the final prediction of the binding free energies. This use of a two-level scoring makes PAS-Dock computationally efficient, and well suited for virtual screening. The PAS-Dock score function is trained on 218 X-ray structures of protein- ligand complexes with experimental binding affinities. The performance of PAS-Dock is compared to two other docking methods, AutoDock and MOE-Dock, with respect to both accuracy and computational efficiency. According to this study, PAS-Dock is more computationally efficient than both AutoDock and MOE-Dock, and gives a better prediction of the free energies of binding. PAS-Dock is also more robust against structural variations than AutoDock.

  4. LC2, the Chlamydomonas Homologue of the t Complex-encoded Protein Tctex2, Is Essential for Outer Dynein Arm Assembly

    Science.gov (United States)

    Pazour, Gregory J.; Koutoulis, Anthony; Benashski, Sharon E.; Dickert, Bethany L.; Sheng, Hong; Patel-King, Ramila S.; King, Stephen M.; Witman, George B.

    1999-01-01

    Tctex2 is thought to be one of the distorter genes of the mouse t haplotype. This complex greatly biases the segregation of the chromosome that carries it such that in heterozygous +/t males, the t haplotype is transmitted to >95% of the offspring, a phenomenon known as transmission ratio distortion. The LC2 outer dynein arm light chain of Chlamydomonas reinhardtii is a homologue of the mouse protein Tctex2. We have identified Chlamydomonas insertional mutants with deletions in the gene encoding LC2 and demonstrate that the LC2 gene is the same as the ODA12 gene, the product of which had not been identified previously. Complete deletion of the LC2/ODA12 gene causes loss of all outer arms and a slow jerky swimming phenotype. Transformation of the deletion mutant with the cloned LC2/ODA12 gene restores the outer arms and rescues the motility phenotype. Therefore, LC2 is required for outer arm assembly. The fact that LC2 is an essential subunit of flagellar outer dynein arms allows us to propose a detailed mechanism whereby transmission ratio distortion is explained by the differential binding of mutant (t haplotype encoded) and wild-type dyneins to the axonemal microtubules of t-bearing or wild-type sperm, with resulting differences in their motility. PMID:10512883

  5. The Canadian Armed Forces “YouTube War”: A Cross-Border Military-Social Media Complex

    Directory of Open Access Journals (Sweden)

    Tanner Mirrlees

    2015-06-01

    Full Text Available The goal of this paper is to conceptualize, contextualize, and critically analyze the Canadian Armed Forces’ (CAF use of YouTube to promote itself, recruit soldiers, and frame its role in the post-9/11 U.S.-led NATO war in Afghanistan. The first section of this paper engages with scholarship on war and the media, the military-industrial-communications complex (MICC, and YouTube War to conceptualize YouTube as a tool and contested battle-space of 21st century new media wars. The second section contextualizes the rise of the CAF’s YouTube channels—Canadian Forces and Canadian Army—with regard to post-9/11 Canadian foreign policy, the growth of the Canadian military publicity state, the creeping militarization of culture, and the CAF’s “social media policy”. The third section conceptualizes the CAF’s two YouTube channels as tools and spaces of its publicity front; then, through a synoptic critical overview of numerous CAF-generated YouTube videos, it shows how the CAF uses YouTube to recruit personnel and frame its role in the war in Afghanistan. The conclusion discusses the characteristics of this cross-border military-social media complex and its contradictions, namely, the spread of pacifist and veteran-generated videos that contest the war in Afghanistan. Overall, the paper offers an initial political-economy of communication of the CAF’s foray into the global battle-space of the Internet and its use of YouTube for publicity.

  6. Molecular docking and molecular dynamics simulation studies on Thermus thermophilus leucyl-tRNA synthetase complexed with different amino acids and pre-transfer editing substrates

    Directory of Open Access Journals (Sweden)

    Rayevsky A. V.

    2016-02-01

    Full Text Available Aim. To investigate the structural bases for the amino acid selectivity of the Thermus thermophilus leucyl-tRNA synthetase (LeuRSTT aminoacylation site and to disclose the binding pattern of pre-transfer editing substrates. Methods. Eight amino acids proposed as semi-cognate substrates for aminoacylation and eight aminoacyl-adenylates (formed from AMP and eight amino acids were prepared in zwitterions form. The protein structure with a co-crystallized substrate in the aminoacylation site [PDBID: 1OBH] was taken from RCSB. Docking settings and evaluation of substrate efficiency were followed by twofold docking function analysis for each conformation with Gold CCDC. The molecular dynamics simulation was performed using Gromacs. The procedures of relaxation and binding study were separated in two different subsequent simulations for 50ns and 5ns. Results. The evaluation of substrate efficiency for 8 amino acids by twofold docking function analysis, based on score values,has shown that the ligands of LeuRSTT can be positioned in the following order: Leu>Nva>Hcy>Nle>Met>Cys>Ile >Val. MD simulation has revealed lower electrostatic interactions of isoleucine with the active site of the enzyme compared with those for norvaline and leucine. In the case of aminoacyl-adenylates no significant differences were found based on score values for both GoldScore and Asp functions. Molecular dynamics of leucyl-, isoleucyl- and norvalyl-adenylates showed that the most stable and conformationally favorable is leucine, then follow norvaline and isoleucine. It has been also found that the TYR43 of the active site covers carboxyl group of leucine and norvaline like a shield and deflected towards isoleucine, allowing water molecules to come closer. Conclusions. In this study we revealed some structural basis for screening unfavorable substrates by shape, size and flexibility of a radical. The results obtained for different amino acids by molecular docking and MD studies

  7. Flexible Ligand Docking Using Evolutionary Algorithms

    DEFF Research Database (Denmark)

    Thomsen, Rene

    2003-01-01

    The docking of ligands to proteins can be formulated as a computational problem where the task is to find the most favorable energetic conformation among the large space of possible protein–ligand complexes. Stochastic search methods such as evolutionary algorithms (EAs) can be used to sample large...

  8. Evaluation of molecular docking using polynomial empirical scoring functions.

    Science.gov (United States)

    Dias, Raquel; Timmers, Luis Fernando Saraiva Macedo; Caceres, Rafael Andrade; de Azevedo, Walter Filgueira

    2008-12-01

    Molecular docking simulations are of pivotal importance for analysis of protein-ligand interactions and also an essential resource for virtual-screening initiatives. In molecular docking simulations several possible docked structures are generated, which create an ensemble of structures representing binary complexes. Therefore, it is crucial to find the best solution for the simulation. One approach to this problem is to employ empirical scoring function to identify the best docked structure. It is expected that scoring functions show a descriptive funnel-shaped energy surface without many false minima to impair the efficiency of conformational sampling. We employed this methodology against a test set with 300 docked structures. Docking simulations of these ligands against enzyme binding pocket indicated a funnel-shaped behavior of the complexation for this system. This review compares a set of recently proposed polynomial empirical scoring functions, implemented in a program called POLSCORE, with two popular scoring function programs (XSCORE and DrugScore). Overall comparison indicated that POLSCORE works better to predict the correct docked position, for the ensemble of docked structures analyzed in the present work.

  9. Synthesis, spectroscopic, molecular orbital calculation, cytotoxic, molecular docking of DNA binding and DNA cleavage studies of transition metal complexes with N-benzylidene-N'-salicylidene-1,1-diaminopropane

    Science.gov (United States)

    Al-Mogren, Muneerah M.; Alaghaz, Abdel-Nasser M. A.; Elbohy, Salwa A. H.

    2013-10-01

    Eight mononuclear chromium(III), manganese(II), iron(III), cobalt(II), nickel(II), copper(II), zinc(II) and cadmium(II) complexes of Schiff's base ligand were synthesized and determined by different physical techniques. The complexes are insoluble in common organic solvents but soluble in DMF and DMSO. The measured molar conductance values in DMSO indicate that the complexes are non-electrolytic in nature. All the eight metal complexes have been fully characterized with the help of elemental analyses, molecular weights, molar conductance values, magnetic moments and spectroscopic data. The analytical data helped to elucidate the structure of the metal complexes. The Schiff base is found to act as tridentate ligand using N2O donor set of atoms leading to an octahedral geometry for the complexes around all the metal ions. Quantum chemical calculations were performed with semi-empirical method to find the optimum geometry of the ligand and its complexes. Additionally in silico, the docking studies and the calculated pharmacokinetic parameters show promising futures for application of the ligand and complexes as high potency agents for DNA binding activity. The interaction of the complexes with calf thymus DNA (CT-DNA) has been investigated by UV absorption method, and the mode of CT-DNA binding to the complexes has been explored. Furthermore, the DNA cleavage activity by the complexes was performed. The Schiff base and their complexes have been screened for their antibacterial activity against bacterial strains [Staphylococcus aureus (RCMB010027), Staphylococcus epidermidis (RCMB010024), Bacillis subtilis (RCMB010063), Proteous vulgaris (RCMB 010085), Klebsiella pneumonia (RCMB 010093) and Shigella flexneri (RCMB 0100542)] and fungi [(Aspergillus fumigates (RCMB 02564), Aspergillus clavatus (RCMB 02593) and Candida albicans (RCMB05035)] by disk diffusion method. All the metal complexes have potent biocidal activity than the free ligand.

  10. New palladium(II) and platinum(II) 5,5-diethylbarbiturate complexes with 2-phenylpyridine, 2,2'-bipyridine and 2,2'-dipyridylamine: synthesis, structures, DNA binding, molecular docking, cellular uptake, antioxidant activity and cytotoxicity.

    Science.gov (United States)

    Icsel, Ceyda; Yilmaz, Veysel T; Kaya, Yunus; Samli, Hale; Harrison, William T A; Buyukgungor, Orhan

    2015-04-21

    Novel palladium(ii) and platinum(ii) complexes of 5,5-diethylbarbiturate (barb) with 2-phenylpyridine (Hppy), 2,2'-bipyridine (bpy) and 2,2'-dipyridylamine (dpya) have been prepared and characterized by elemental analysis, IR, UV-Vis, NMR and ESI-MS. Single-crystal diffraction measurements show that complex consists of binuclear [Pd2(μ-barb-κN,O)2(ppy-κN,C)2] moieties, while complexes are mononuclear, [M(barb-κN)2(L-κN,N')] (L = bpy or dpya). has a composition of [Pt(dpya-κN,N')2][Ag(barb-κN)2]2·4H2O and was assumed to have a structure of [Pt(barb-κN)(Hppy-κN)(ppy-κN,C)]·3H2O. The complexes were found to exhibit significant DNA binding affinity by a non-covalent binding mode, in accordance with molecular docking studies. In addition, complexes and displayed strong binding with supercoiled pUC19 plasmid DNA. Cellular uptake studies were performed to assess the subcellular localization of the selected complexes. A moderate radical scavenging activity of and was confirmed by DPPH and ABTS tests. Complexes , , and showed selectivity against HT-29 (colon) cell line.

  11. Androgynous, Reconfigurable Closed Loop Feedback Controlled Low Impact Docking System With Load Sensing Electromagnetic Capture Ring

    Science.gov (United States)

    Lewis, James L. (Inventor); Carroll, Monty B. (Inventor); Morales, Ray H. (Inventor); Le, Thang D. (Inventor)

    2002-01-01

    The present invention relates to a fully androgynous, reconfigurable closed loop feedback controlled low impact docking system with load sensing electromagnetic capture ring. The docking system of the present invention preferably comprises two Docking- assemblies, each docking assembly comprising a load sensing ring having an outer face, one of more electromagnets, one or more load cells coupled to said load sensing ring. The docking assembly further comprises a plurality of actuator arms coupled to said load sensing ring and capable of dynamically adjusting the orientation of said load sensing ring and a reconfigurable closed loop control system capable of analyzing signals originating from said plurality of load cells and of outputting real time control for each of the actuators. The docking assembly of the present invention incorporates an active load sensing system to automatically dynamically adjust the load sensing ring during capture instead of requiring significant force to push and realign the ring.

  12. A New Scoring Function for Molecular Docking Based on AutoDock and AutoDock Vina.

    Science.gov (United States)

    Tanchuk, Vsevolod Yu; Tanin, Volodymyr O; Vovk, Andriy I; Poda, Gennady

    2015-01-01

    Molecular docking of small molecules in the protein binding sites is the most widely used computational technique in modern structure-based drug discovery. Although accurate prediction of binding modes of small molecules can be achieved in most cases, estimation of their binding affinities remains mediocre at best. As an attempt to improve the correlation between the inhibitory constants, pKi, and scoring, we created a new, hybrid scoring function. The new function is a linear combination of the terms of the scoring functions of AutoDock and AutoDock Vina. It was trained on 2,412 protein-ligand complexes from the PDBbind database (www.pdbbind.org.cn, version 2012) and validated on a set of 313 complexes released in the 2013 version as a test set. The new function was included in a modified version of AutoDock. The hybrid scoring function showed a statistically significant improvement in both training and test sets in terms of correlation with and root mean square and mean absolute errors in prediction of pKi values. It was also tested on the CSAR 2014 Benchmark Exercise dataset (team T) and produced reasonably good results.

  13. Synthesis, characterization, crystal structure, DNA and BSA binding, molecular docking and in vitro anticancer activities of a mononuclear dioxido-uranium(VI) complex derived from a tridentate ONO aroylhydrazone.

    Science.gov (United States)

    Mohamadi, Maryam; Ebrahimipour, S Yousef; Castro, Jesus; Torkzadeh-Mahani, Masoud

    2016-05-01

    A mononuclear dioxido-uranium(IV) complex [UO2(L)(DMSO)2], was prepared from the reaction of (2-hydroxy-3-methoxybenzylidene)benzohydrazide [HL] with UO2(OAc)2·2H2O in DMSO. The obtained complex was fully characterized. Single crystal X-ray diffraction analysis of [UO2(L)(DMSO)2] revealed that U(VI) ion has been coordinated by ONO donor atoms of the dianionic ligand (L(2-)), oxo groups and two DMSO molecules in a pentagonal bipyramid geometry. In addition, interactions of the complex with salmon sperm DNA and bovine serum albumin (BSA) were thoroughly investigated using UV-vis absorption, voltammetry and molecular docking methods. The experimental studies showed an intercalative mode of interaction between the complex and DNA. Experiments on BSA interaction indicated a change in the polarity of the environment surrounded the complex as a result of the interaction between BSA and [UO2(L)(DMSO)2]. Finally, MTT assays indicated that the U(VI) complex had excellent cytotoxicity against human carcinoma cell lines of MCF-7, HPG-2, and HT-29, with IC50 values of 8.4, 10.6 and 10.0μM, respectively.

  14. Protein-Ligand Docking Based on Beta-Shape

    Science.gov (United States)

    Kim, Chong-Min; Won, Chung-In; Kim, Jae-Kwan; Ryu, Joonghyun; Bhak, Jong; Kim, Deok-Soo

    Protein-ligand docking is to predict the location and orientation of a ligand with respect to a protein within its binding site, and has been known to be essential for the development of new drugs. The protein-ligand docking problem is usually formulated as an energy minimization problem to identify the docked conformation of the ligand. A ligand usually docks around a depressed region, called a pocket, on the surface of a protein. Presented in this paper is a docking method, called BetaDock, based on the newly developed geometric construct called the β-shape and the β-complex. To cope with the computational intractability, the global minimum of the potential energy function is searched using the genetic algorithm. The proposed algorithm first locates initial chromosomes at some locations within the pocket recognized according to the local shape of the β-shape. Then, the algorithm proceeds generations by taking advantage of powerful properties of the β-shape to achieve an extremely fast and good solution. We claim that the proposed method is much faster than other popular docking softwares including AutoDock.

  15. Biological evaluation of {sup 153}Sm and {sup 166}Ho complexes with tetraazamacrocycles containing methylcarboxylate and/or methylphosphonate pendant arms

    Energy Technology Data Exchange (ETDEWEB)

    Marques, F.; Gano, L.; Campello, M.P.; Lacerda, S.; Santos, I. [Inst. Tecnologico e Nuclear, Sacavem (Portugal)

    2007-07-01

    {sup 153}Sm and {sup 166}Ho complexes with two series of tetraazamacrocyclic ligands containing methylcarboxylate and/or methylphosphonate pendant arms were synthesized and their charge, lipophilicity, protein binding and in vitro and in vivo behaviour evaluated. The first series has the same backbone, a 14-membered tetraazamacrocycle containing a pyridine unit with different pendant arms, namely methylcarboxylates (ac{sub 3}py14) or methylphosphonates (MeP{sub 2}py14 and P{sub 3}py14). The second series comprises 12- to 14-membered tetraazamacrocycles having methylcarboxylates and/or methylphosphonates as pendant arms (trans-DO2A2P, TRITA, TRITP, TETA and TETP). The {sup 153}Sm/{sup 166}Ho complexes with the 14-membered tetraazamacrocycles containing the pyridine unit are neutral, hydrophilic, have a significant plasmatic protein binding, are unstable in vivo and present a slow rate of radioactivity excretion and high hepatic retention. {sup 153}Sm/{sup 166}Ho complexes with the 12- to 14-membered tetraazamacrocycles are quantitatively prepared, except those with TETP. These complexes are hydrophilic, have an overall negative charge and present a medium to low plasmatic protein binding. The {sup 153}Sm/{sup 166}Ho-trans-DO2A2P, {sup 153}Sm/{sup 166}Ho-TRITA and {sup 166}Ho-TRITP complexes are stable in vitro and in vivo, presenting a rapid clearance from main organs and a high rate of whole body radioactivity excretion. Biological profile of {sup 153}Sm/{sup 166}Ho-TRITA complexes makes them promising candidates for therapy when conjugated to a biomolecule, while {sup 166}Ho-TRITP is potentially useful for bone targeting due to its considerable uptake by bone. (orig.)

  16. L-Galactono-1,4-lactone dehydrogenase is an assembly factor of the membrane arm of mitochondrial complex I in Arabidopsis.

    Science.gov (United States)

    Schimmeyer, Joram; Bock, Ralph; Meyer, Etienne H

    2016-01-01

    L-Galactono-1,4-lactone dehydrogenase (GLDH) catalyses the last enzymatic step of the ascorbate biosynthetic pathway in plants. GLDH is localised to mitochondria and several reports have shown that GLDH is associated with complex I of the respiratory chain. In a gldh knock-out mutant, complex I is not detectable, suggesting that GLDH is essential for complex I assembly or stability. GLDH has not been identified as a genuine complex I subunit, instead, it is present in a smaller, lowly abundant version of complex I called complex I*. In addition, GLDH activity has also been detected in smaller protein complexes within mitochondria membranes. Here, we investigated the role of GLDH during complex I assembly. We identified GLDH in complexes co-localising with some complex I assembly intermediates. Using a mutant that accumulates complex I assembly intermediates, we confirmed that GLDH is associated with the complex I assembly intermediates of 400 and 450 kDa. In addition, we detected accumulation of the 200 kDa complex I assembly intermediate in the gldh mutant. Taken together, our data suggest that GLDH is an assembly factor of the membrane arm of complex I. This function appears to be independent of the role of GLDH in ascorbate synthesis, as evidenced by the ascorbate-deficient mutant vtc2-1 accumulating wild-type levels of complex I. Therefore, we propose that GLDH is a dual-function protein that has a second, non-enzymatic function in complex I assembly as a plant-specific assembly factor. We propose an updated model for complex I assembly that includes complex I* as an assembly intermediate.

  17. DockBench as docking selector tool: the lesson learned from D3R Grand Challenge 2015

    Science.gov (United States)

    Salmaso, Veronica; Sturlese, Mattia; Cuzzolin, Alberto; Moro, Stefano

    2016-09-01

    Structure-based drug design (SBDD) has matured within the last two decades as a valuable tool for the optimization of low molecular weight lead compounds to highly potent drugs. The key step in SBDD requires knowledge of the three-dimensional structure of the target-ligand complex, which is usually determined by X-ray crystallography. In the absence of structural information for the complex, SBDD relies on the generation of plausible molecular docking models. However, molecular docking protocols suffer from inaccuracies in the description of the interaction energies between the ligand and the target molecule, and often fail in the prediction of the correct binding mode. In this context, the appropriate selection of the most accurate docking protocol is absolutely relevant for the final molecular docking result, even if addressing this point is absolutely not a trivial task. D3R Grand Challenge 2015 has represented a precious opportunity to test the performance of DockBench, an integrate informatics platform to automatically compare RMDS-based molecular docking performances of different docking/scoring methods. The overall performance resulted in the blind prediction are encouraging in particular for the pose prediction task, in which several complex were predicted with a sufficient accuracy for medicinal chemistry purposes.

  18. A New, Improved Hybrid Scoring Function for Molecular Docking and Scoring Based on AutoDock and AutoDock Vina.

    Science.gov (United States)

    Tanchuk, Vsevolod Yu; Tanin, Volodymyr O; Vovk, Andriy I; Poda, Gennady

    2016-04-01

    Automated docking is one of the most important tools for structure-based drug design that allows prediction of ligand binding poses and also provides an estimate of how well small molecules fit in the binding site of a protein. A new scoring function based on AutoDock and AutoDock Vina has been introduced. The new hybrid scoring function is a linear combination of the two scoring function components derived from a multiple linear regression fitting procedure. The scoring function was built on a training set of 2412 protein-ligand complexes from pdbbind database (www.pdbbind.org.cn, version 2012). A test set of 313 complexes that appeared in the 2013 version was used for validation purposes. The new hybrid scoring function performed better than the original functions, both on training and test sets of protein-ligand complexes, as measured by the non-parametric Pearson correlation coefficient, R, mean absolute error (MAE), and root-mean-square error (RMSE) between the experimental binding affinities and the docking scores. The function also gave one of the best results among more than 20 scoring functions tested on the core set of the pdbbind database. The new AutoDock hybrid scoring function will be implemented in modified version of AutoDock.

  19. AutoDock4(Zn): an improved AutoDock force field for small-molecule docking to zinc metalloproteins.

    Science.gov (United States)

    Santos-Martins, Diogo; Forli, Stefano; Ramos, Maria João; Olson, Arthur J

    2014-08-25

    Zinc is present in a wide variety of proteins and is important in the metabolism of most organisms. Zinc metalloenzymes are therapeutically relevant targets in diseases such as cancer, heart disease, bacterial infection, and Alzheimer's disease. In most cases a drug molecule targeting such enzymes establishes an interaction that coordinates with the zinc ion. Thus, accurate prediction of the interaction of ligands with zinc is an important aspect of computational docking and virtual screening against zinc containing proteins. We have extended the AutoDock force field to include a specialized potential describing the interactions of zinc-coordinating ligands. This potential describes both the energetic and geometric components of the interaction. The new force field, named AutoDock4Zn, was calibrated on a data set of 292 crystal complexes containing zinc. Redocking experiments show that the force field provides significant improvement in performance in both free energy of binding estimation as well as in root-mean-square deviation from the crystal structure pose. The new force field has been implemented in AutoDock without modification to the source code.

  20. Synthesis, crystal structures, molecular docking, in vitro monoamine oxidase-B inhibitory activity of transition metal complexes with 2-{4-[bis (4-fluorophenyl)methyl]piperazin-1-yl} acetic acid

    Science.gov (United States)

    Yang, Dan-dan; Wang, Riu; Zhu, Jin-long; Cao, Qi-yue; Qin, Jie; Zhu, Hai-liang; Qian, Shao-song

    2017-01-01

    Three novel complexes, [Cu(L)2(H2O)](1), [Zn(L)2(H2O)2]·CH3OH·1.5H2O(2), and [Ni(L)2(H2O)1.8]·CH3OH·1.2H2O (3) (HL = 2-{4-[bis(4-fluorophenyl)methyl]pipera-zin-1-yl} acetic acid), were synthesized and structurally determined by single-crystal X-ray diffraction. Molecular docking study preliminarily revealed that complex 1 had potential Monoamine oxidase B inhibitory activity. All acquired compounds were tested against rat brain MAO-B in vitro. In accordance with the result of calculation, it showed complex 1 (IC50 = 1.85 ± 0.31 μM) have good inhibitory activity against MAO-B at the same micromolar concentrations with positive control Iproniazid Phosphate (IP, IC50 = 7.59 ± 1.17 μM). These results indicated that complex 1 was a potent MAO-B inhibitor.

  1. Polymer-like structures of LiSCN, NaSCN, KSCN, RbSCN, and CsSCN complexes with an armed monoaza-15-crown-5 ether bearing a 3',5'-difluoro-4'-hydroxybenzyl group.

    Science.gov (United States)

    Habata, Yoichi; Okazaki, Chizuko; Ogura, Kinuko; Akabori, Sadatoshi; Zhang, Xian X; Bradshaw, Jerald S

    2007-10-01

    Structures of LiSCN, NaSCN, KSCN, RbSCN, and CsSCN complexes with 3',5'-difluoro-4'-hydroxybenzyl-armed monoaza-15-crown-5 ether (5) were investigated. The Li+ and Na+ complexes are (1:1)n polymer-like complexes bridged by hydrogen bonding. On the other hand, the K+, Rb+, and Cs+ complexes are polymer-like complexes bridged by the fluorine atoms of the side arms. The titration calorimetry and 19F NMR titration experiments suggest that one or both fluorine atoms along with the oxygen atom of the phenolic OH group coordinate to the alkali metal ions incorporated in the crown part of a second armed ligand to give polymer-like complexes in solution. The FAB-MS data indicated that larger alkali metal ions form more stable polymer-like complexes.

  2. Star Formation in Spiral Arms

    CERN Document Server

    Elmegreen, Bruce G

    2011-01-01

    The origin and types of spiral arms are reviewed with an emphasis on the connections between these arms and star formation. Flocculent spiral arms are most likely the result of transient instabilities in the gas that promote dense cloud formation, star formation, and generate turbulence. Long irregular spiral arms are usually initiated by gravitational instabilities in the stars, with the gas contributing to and following these instabilities, and star formation in the gas. Global spiral arms triggered by global perturbations, such as a galaxy interaction, can be wavemodes with wave reflection in the inner regions. They might grow and dominate the disk for several rotations before degenerating into higher-order modes by non-linear effects. Interstellar gas flows through these global arms, and through the more transient stellar spiral arms as well, where it can reach a high density and low shear, thereby promoting self-gravitational instabilities. The result is the formation of giant spiral arm cloud complexes,...

  3. Vision-guided heterogeneous mobile robot docking

    Science.gov (United States)

    Spofford, John R.; Blitch, John; Klarquist, William N.; Murphy, Robin R.

    1999-08-01

    Teams of heterogeneous mobile robots are a key aspect of future unmanned system for operations in complex and dynamic urban environments, such as that envisioned by DARPA's Tactical Mobile Robotics program. One examples of an interaction among such team members is the docking of small robot of limited sensory and processing capability with a larger, more capable robot. Applications for such docking include the transfer of power, data, and materia, as well as physically combined maneuver or manipulation. A two-robot system is considered in this paper. The smaller 'throwable' robot contains a video camera capable of imaging the larger 'packable' robot and transmitting the imagery. The packable robot can both sense the throwable robot through an onboard camera, as well as sense itself through the throwable robot's transmitted video, and is capable of processing imagery from either source. This paper describes recent results in the development of control and sensing strategies for automatic mid-range docking of these two robots. Decisions addressed include the selection of which robot's image sensor to use and which robot to maneuver. Initial experimental results are presented for docking using sensor data from each robot.

  4. Investigation of MM-PBSA rescoring of docking poses.

    Science.gov (United States)

    Thompson, David C; Humblet, Christine; Joseph-McCarthy, Diane

    2008-05-01

    Target-based virtual screening is increasingly used to generate leads for targets for which high quality three-dimensional (3D) structures are available. To allow large molecular databases to be screened rapidly, a tiered scoring scheme is often employed whereby a simple scoring function is used as a fast filter of the entire database and a more rigorous and time-consuming scoring function is used to rescore the top hits to produce the final list of ranked compounds. Molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) approaches are currently thought to be quite effective at incorporating implicit solvation into the estimation of ligand binding free energies. In this paper, the ability of a high-throughput MM-PBSA rescoring function to discriminate between correct and incorrect docking poses is investigated in detail. Various initial scoring functions are used to generate docked poses for a subset of the CCDC/Astex test set and to dock one set of actives/inactives from the DUD data set. The effectiveness of each of these initial scoring functions is discussed. Overall, the ability of the MM-PBSA rescoring function to (i) regenerate the set of X-ray complexes when docking the bound conformation of the ligand, (ii) regenerate the X-ray complexes when docking conformationally expanded databases for each ligand which include "conformation decoys" of the ligand, and (iii) enrich known actives in a virtual screen for the mineralocorticoid receptor in the presence of "ligand decoys" is assessed. While a pharmacophore-based molecular docking approach, PhDock, is used to carry out the docking, the results are expected to be general to use with any docking method.

  5. Synthesis and structure elucidation of new μ-oxamido-bridged dicopper(II) complex with in vitro anticancer activity: A combined study from experiment verification and docking calculation on DNA/protein-binding property.

    Science.gov (United States)

    Zhu, Ling; Zheng, Kang; Li, Yan-Tuan; Wu, Zhi-Yong; Yan, Cui-Wei

    2016-02-01

    A new oxamido-bridged dicopper(II) complex with formula of [Cu2(deap)(pic)2], where H2deap and pic represent N,N'-bis[3-(diethylamino)propyl]oxamide and picrate, respectively, was synthesized and characterized by elemental analyses, molar conductance measurements, IR and electronic spectral study, and single-crystal X-ray diffraction. The crystal structure analyses revealed that the two copper(II) atoms in the dicopper(II) complex are bridged by the trans-deap(2-) ligand with the distances of 5.2116(17)Å, and the coordination environment around the copper(II) atoms can be described as a square-planar geometry. Hydrogen bonding and π-π stacking interactions link the dicopper(II) complex into a three-dimensional infinite network. The DNA/protein-binding properties of the complex are investigated by molecular docking and experimental assays. The results indicate that the dicopper(II) complex can interact with HS-DNA in the mode of intercalation and effectively quench the intrinsic fluorescence of protein BSA by 1:1 binding with the most possible binding site in the proximity of Trp134. The in vitro anticancer activities suggest that the complex is active against the selected tumor cell lines, and IC50 values for SMMC-7721 and HepG2 are lower than cisplatin. The effects of the electron density distribution of the terminal ligand and the chelate ring arrangement around copper(II) ions bridged by symmetric N,N'-bis(substituted)oxamides on DNA/BSA-binding ability and in vitro anticancer activity are preliminarily discussed.

  6. ATTRACT and PTools: open source programs for protein-protein docking.

    Science.gov (United States)

    Schneider, Sebastian; Saladin, Adrien; Fiorucci, Sébastien; Prévost, Chantal; Zacharias, Martin

    2012-01-01

    The prediction of the structure of protein-protein complexes based on structures or structural models of isolated partners is of increasing importance for structural biology and bioinformatics. The ATTRACT program can be used to perform systematic docking searches based on docking energy minimization. It is part of the object-oriented PTools library written in Python and C++. The library contains various routines to manipulate protein structures, to prepare and perform docking searches as well as analyzing docking results. It also intended to facilitate further methodological developments in the area of macromolecular docking that can be easily integrated. Here, we describe the application of PTools to perform systematic docking searches and to analyze the results. In addition, the possibility to perform multi-component docking will also be presented.

  7. Spacecraft rendezvous and docking

    DEFF Research Database (Denmark)

    Jørgensen, John Leif

    1999-01-01

    procedures. The method described generates, based on a single camera and a priory information about the target vehicle and orbit data, all necessary guidance information for closed-loop autonomous navigation, from first detection at far distance, to a close up a hold point. Furthermore, the system provide...... been based entirely on direct human supervision and control. This paper describes a vision-based system and methodology, that autonomously generates accurate guidance information that may assist a human operator in performing the tasks associated with both the rendezvous and docking navigation...

  8. A New Approach for Flexible Molecular Docking Based on Swarm Intelligence

    Directory of Open Access Journals (Sweden)

    Yi Fu

    2015-01-01

    Full Text Available Molecular docking methods play an important role in the field of computer-aided drug design. In the work, on the basis of the molecular docking program AutoDock, we present QLDock as a tool for flexible molecular docking. For the energy evaluation, the algorithm uses the binding free energy function that is provided by the AutoDock 4.2 tool. The new search algorithm combines the features of a quantum-behaved particle swarm optimization (QPSO algorithm and local search method of Solis and Wets for solving the highly flexible protein-ligand docking problem. We compute the interaction of 23 protein-ligand complexes and compare the results with those of the QDock and AutoDock programs. The experimental results show that our approach leads to substantially lower docking energy and higher docking precision in comparison to Lamarckian genetic algorithm and QPSO algorithm alone. QPSO-ls algorithm was able to identify the correct binding mode of 74% of the complexes. In comparison, the accuracy of QPSO and LGA is 52% and 61%, respectively. This difference in performance rises with increasing complexity of the ligand. Thus, the novel algorithm QPSO-ls may be used to dock ligand with many rotatable bonds with high accuracy.

  9. Synthesis, characterization and biological application of four novel metal-Schiff base complexes derived from allylamine and their interactions with human serum albumin: Experimental, molecular docking and ONIOM computational study.

    Science.gov (United States)

    Kazemi, Zahra; Rudbari, Hadi Amiri; Sahihi, Mehdi; Mirkhani, Valiollah; Moghadam, Majid; Tangestaninejad, Shahram; Mohammadpoor-Baltork, Iraj; Gharaghani, Sajjad

    2016-09-01

    Novel metal-based drug candidate including VOL2, NiL2, CuL2 and PdL2 have been synthesized from 2-hydroxy-1-allyliminomethyl-naphthalen ligand and have been characterized by means of elemental analysis (CHN), FT-IR and UV-vis spectroscopies. In addition, (1)H and (13)C NMR techniques were employed for characterization of the PdL2 complex. Single-crystal X-ray diffraction technique was utilized to characterise the structure of the complexes. The Cu(II), Ni(II) and Pd(II) complexes show a square planar trans-coordination geometry, while in the VOL2, the vanadium center has a distorted tetragonal pyramidal N2O3 coordination sphere. The HSA-binding was also determined, using fluorescence quenching, UV-vis spectroscopy, and circular dichroism (CD) titration method. The obtained results revealed that the HSA affinity for binding the synthesized compounds follows as PdL2>CuL2>VOL2>NiL2, indicating the effect of metal ion on binding constant. The distance between these compounds and HSA was obtained based on the Förster's theory of non-radiative energy transfer. Furthermore, computational methods including molecular docking and our Own N-layered Integrated molecular Orbital and molecular Mechanics (ONIOM) were carried out to investigate the HSA-binding of the compounds. Molecular docking calculation indicated the existence of hydrogen bond between amino acid residues of HSA and all synthesized compounds. The formation of the hydrogen bond in the HSA-compound systems leads to their stabilization. The ONIOM method was utilized in order to investigate HSA binding of compounds more precisely in which molecular mechanics method (UFF) and semi empirical method (PM6) were selected for the low layer and the high layer, respectively. The results show that the structural parameters of the compounds changed along with binding to HSA, indicating the strong interaction between the compounds and HSA. The value of binding constant depends on the extent of the resultant changes. This

  10. The Asteroid Redirect Mission (ARM)

    Science.gov (United States)

    Abell, Paul; Gates, Michele; Johnson, Lindley; Chodas, Paul; Mazanek, Dan; Reeves, David; Ticker, Ronald

    2016-07-01

    To achieve its long-term goal of sending humans to Mars, the National Aeronautics and Space Administration (NASA) plans to proceed in a series of incrementally more complex human spaceflight missions. Today, human flight experience extends only to Low-Earth Orbit (LEO), and should problems arise during a mission, the crew can return to Earth in a matter of minutes to hours. The next logical step for human spaceflight is to gain flight experience in the vicinity of the Moon. These cis-lunar missions provide a "proving ground" for the testing of systems and operations while still accommodating an emergency return path to the Earth that would last only several days. Cis-lunar mission experience will be essential for more ambitious human missions beyond the Earth-Moon system, which will require weeks, months, or even years of transit time. In addition, NASA has been given a Grand Challenge to find all asteroid threats to human populations and know what to do about them. Obtaining knowledge of asteroid physical properties combined with performing technology demonstrations for planetary defense provide much needed information to address the issue of future asteroid impacts on Earth. Hence the combined objectives of human exploration and planetary defense give a rationale for the Asteroid Re-direct Mission (ARM). Mission Description: NASA's ARM consists of two mission segments: 1) the Asteroid Redirect Robotic Mission (ARRM), the first robotic mission to visit a large (greater than ~100 m diameter) near-Earth asteroid (NEA), collect a multi-ton boulder from its surface along with regolith samples, demonstrate a planetary defense technique, and return the asteroidal material to a stable orbit around the Moon; and 2) the Asteroid Redirect Crewed Mission (ARCM), in which astronauts will take the Orion capsule to rendezvous and dock with the robotic vehicle, conduct multiple extravehicular activities to explore the boulder, and return to Earth with samples. NASA's proposed

  11. DockingApp: a user friendly interface for facilitated docking simulations with AutoDock Vina

    Science.gov (United States)

    Di Muzio, Elena; Toti, Daniele; Polticelli, Fabio

    2017-02-01

    Molecular docking is a powerful technique that helps uncover the structural and energetic bases of the interaction between macromolecules and substrates, endogenous and exogenous ligands, and inhibitors. Moreover, this technique plays a pivotal role in accelerating the screening of large libraries of compounds for drug development purposes. The need to promote community-driven drug development efforts, especially as far as neglected diseases are concerned, calls for user-friendly tools to allow non-expert users to exploit the full potential of molecular docking. Along this path, here is described the implementation of DockingApp, a freely available, extremely user-friendly, platform-independent application for performing docking simulations and virtual screening tasks using AutoDock Vina. DockingApp sports an intuitive graphical user interface which greatly facilitates both the input phase and the analysis of the results, which can be visualized in graphical form using the embedded JMol applet. The application comes with the DrugBank set of more than 1400 ready-to-dock, FDA-approved drugs, to facilitate virtual screening and drug repurposing initiatives. Furthermore, other databases of compounds such as ZINC, available also in AutoDock format, can be readily and easily plugged in.

  12. DockingApp: a user friendly interface for facilitated docking simulations with AutoDock Vina

    Science.gov (United States)

    Di Muzio, Elena; Toti, Daniele; Polticelli, Fabio

    2017-01-01

    Molecular docking is a powerful technique that helps uncover the structural and energetic bases of the interaction between macromolecules and substrates, endogenous and exogenous ligands, and inhibitors. Moreover, this technique plays a pivotal role in accelerating the screening of large libraries of compounds for drug development purposes. The need to promote community-driven drug development efforts, especially as far as neglected diseases are concerned, calls for user-friendly tools to allow non-expert users to exploit the full potential of molecular docking. Along this path, here is described the implementation of DockingApp, a freely available, extremely user-friendly, platform-independent application for performing docking simulations and virtual screening tasks using AutoDock Vina. DockingApp sports an intuitive graphical user interface which greatly facilitates both the input phase and the analysis of the results, which can be visualized in graphical form using the embedded JMol applet. The application comes with the DrugBank set of more than 1400 ready-to-dock, FDA-approved drugs, to facilitate virtual screening and drug repurposing initiatives. Furthermore, other databases of compounds such as ZINC, available also in AutoDock format, can be readily and easily plugged in.

  13. Combining pharmacophore search, automated docking, and molecular dynamics simulations as a novel strategy for flexible docking. Proof of concept: docking of arginine-glycine-aspartic acid-like compounds into the alphavbeta3 binding site.

    Science.gov (United States)

    Moitessier, Nicolas; Henry, Christophe; Maigret, Bernard; Chapleur, Yves

    2004-08-12

    A novel and highly efficient flexible docking approach is presented where the conformations (internal degrees of freedom) and orientations (external degrees of freedom) of the ligands are successively considered. This hybrid method takes advantage of the synergistic effects of structure-based and ligand-based drug design techniques. Preliminary antagonist-derived pharmacophore determination provides the postulated bioactive conformation. Subsequent docking of this pharmacophore to the receptor crystal structure results in a postulated pharmacophore/receptor binding mode. Pharmacophore-oriented docking of antagonists is subsequently achieved by matching ligand interacting groups with pharmacophore points. Molecular dynamics in water refines the proposed complexes. To validate the method, arginine-glycine-aspartic acid (RGD) containing peptides, pseudopeptides, and RGD-like antagonists were docked to the crystal structure of alphavbeta3 holoprotein and apoprotein. The proposed directed docking was found to be more accurate, faster, and less biased with respect to the protein structure (holo and apoprotein) than DOCK, Autodock, and FlexX docking methods. The successful docking of an antagonist recently cocrystallized with the receptor to both apo and holoprotein is particularly appealing. The results summarized in this report illustrated the efficiency of our light CoMFA/rigid body docking hybrid method.

  14. A DIVERSE SOCIETY, A REPRESENTATIVE MILITARY? THE COMPLEXITY OF MANAGING DIVERSITY IN THE SOUTH AFRICAN ARMED FORCES

    Directory of Open Access Journals (Sweden)

    Lindy Heinecken

    2011-08-01

    Full Text Available After providing a brief background as to why issues of diversity managementwithin armed forces have become important internationally, this article outlines thediversity challenges facing the South African National Defence Force (SANDF.The first part of the article describes how the racial, language/ethnic and genderprofile of the SANDF has changed since 1994 and the tensions this has evoked. Thesecond part provides a brief conceptual framework against which diversitymanagement in the SANDF can be interpreted, whereafter the various diversitymanagement programmes instituted over the years to cultivate a respect for diversityare outlined. It is argued that the predominant emphasis on ‘workplace diversity’ atthe cost of ‘valuing diversity’ has meant that existing stereotypes and tensionswithin the ranks have remained, with dire consequences not only for thecohesiveness and effectiveness of the SANDF, but also for civil-military relations.

  15. Syntheses, structural variations and fluorescence studies of two dinuclear zinc(II) complexes of a Schiff base ligand with an extended carboxylate side arm

    Science.gov (United States)

    Shit, Shyamapada; Sasmal, Ashok; Dhal, Piu; Rizzoli, Corrado; Mitra, Samiran

    2016-03-01

    A potentially tetradentate Schiff base ligand containing carboxylic acid group, HL, (E)-2-((pyridin-2-yl)methyleneamino)-5-chlorobenzoic acid is synthesized and characterized. Reaction of HL with hydrated zinc(II) trichloroacetate and zinc(II) trifluoroacetate under similar reaction condition yields two discrete dinuclear complexes, [Zn(L)(Cl)]2 (1) and [Zn(L)(CF3COO)]2 (2) and characterized by different physicochemical methods. Single crystal X-ray structural characterization reveals different ligating properties of the coordinated anionic ligand (L-) in its zinc(II) complexes. The side arm carboxylate of L- shows μ1,3-carboxylato-bridging mode in 1 and connects zinc(II) atoms in syn-anti fashion while it exhibits a μ1,1-carboxylato-bridging mode in 2. The metal ions display distorted square pyramidal geometries in both the structures and associated with different degrees of distortions. The fluorescence spectra of HL and its zinc(II) complexes recorded in methanol at room temperature which reveal the enhancement of emission intensity for the complexes compared to that of the free ligand. Thermogravimetric analyses (TGA) reveal high thermal stabilities of the complexes.

  16. Chunk concatenation evolves with practice and sleep-related enhancement consolidation in a complex arm movement sequence

    Directory of Open Access Journals (Sweden)

    Blischke Klaus

    2016-06-01

    Full Text Available This paper addresses the notion of chunk concatenation being associated with sleep-related enhancement consolidation of motor sequence memory, thereby essentially contributing to improvements in sequence execution speed. To this end, element movement times of a multi-joint arm movement sequence incorporated in a recent study by Malangré et al. (2014 were reanalyzed. As sequence elements differed with respect to movement distance, element movement times had to be purged from differences solely due to varying trajectory lengths. This was done by dividing each element movement time per subject and trial block by the respective “reference movement time” collected from subjects who had extensively practiced each sequence element in isolation. Any differences in these “relative element movement times” were supposed to reflect element-specific “production costs” imposed solely by the sequence context. Across all subjects non-idiosyncratic, lasting sequence segmentation was shown, and four possible concatenation points (i.e. transition points between successive chunks within the original arm movement sequence were identified. Based on theoretical suppositions derived from previous work with the discrete sequence production task and the dual processor model (Abrahamse et al., 2013, significantly larger improvements in transition speed occurring at these four concatenation points as compared to the five fastest transition positions within the sequence (associated with mere element execution were assumed to indicate increased chunk concatenation. As a result, chunk concatenation was shown to proceed during acquisition with physical practice, and, most importantly, to significantly progress some more during retention following a night of sleep, but not during a waking interval.

  17. The Oligomeric Outer Dynein Arm Assembly Factor CCDC103 Is Tightly Integrated within the Ciliary Axoneme and Exhibits Periodic Binding to Microtubules*

    Science.gov (United States)

    King, Stephen M.; Patel-King, Ramila S.

    2015-01-01

    CCDC103 is an ∼29-kDa protein consisting of a central RPAP3_C domain flanked by N- and C-terminal coiled coils. Defects in CCDC103 lead to primary ciliary dyskinesia caused by the loss of outer dynein arms. This protein is present along the entire length of the ciliary axoneme and does not require other dynein or docking complex components for its integration. Unlike other known dynein assembly factors within the axoneme, CCDC103 is not solubilized by 0.6 m NaCl and requires more chaotropic conditions, such as 0.5 m KI. Alternatively, it can be extracted using 0.3% sarkosyl. CCDC103 forms stable dimers and other oligomers in solution through interactions involving the central domain. The smallest particle observed by dynamic light scattering has a hydrodynamic diameter of ∼25 nm. Furthermore, CCDC103 binds microtubules directly, forming ∼9-nm diameter particles that exhibit a 12-nm spacing on the microtubule lattice, suggesting that there may be two CCDC103 units per outer arm dynein repeat. Although the outer dynein arm docking complex is necessary to form arrays of dyneins along microtubules, it is not sufficient to set up a single array in a precise location on each axonemal doublet. We propose that CCDC103 helps generate a high-affinity site on the doublets for outer arm assembly, either through direct interactions or indirectly, perhaps by modifying the underlying microtubule lattice. PMID:25572396

  18. Three Members of the LC8/DYNLL Family Are Required for Outer Arm Dynein Motor Function

    Science.gov (United States)

    Tanner, Christopher A.; Rompolas, Panteleimon; Patel-King, Ramila S.; Gorbatyuk, Oksana; Wakabayashi, Ken-ichi; Pazour, Gregory J.

    2008-01-01

    The highly conserved LC8/DYNLL family proteins were originally identified in axonemal dyneins and subsequently found to function in multiple enzyme systems. Genomic analysis uncovered a third member (LC10) of this protein class in Chlamydomonas. The LC10 protein is extracted from flagellar axonemes with 0.6 M NaCl and cofractionates with the outer dynein arm in sucrose density gradients. Furthermore, LC10 is specifically missing only from axonemes of those strains that fail to assemble outer dynein arms. Previously, the oda12-1 insertional allele was shown to lack the Tctex2-related dynein light chain LC2. The LC10 gene is located ∼2 kb from that of LC2 and is also completely missing from this mutant but not from oda12-2, which lacks only the 3′ end of the LC2 gene. Although oda12-1 cells assemble outer arms that lack only LC2 and LC10, this strain exhibits a flagellar beat frequency that is consistently less than that observed for strains that fail to assemble the entire outer arm and docking complex (e.g., oda1). These results support a key regulatory role for the intermediate chain/light chain complex that is an integral and highly conserved feature of all oligomeric dynein motors. PMID:18579685

  19. Technology Development of Automated Rendezvous and Docking/Capture Sensors and Docking Mechanism for the Asteroid Redirect Crewed Mission

    Science.gov (United States)

    Hinkel, Heather; Strube, Matthew; Zipay, John J.; Cryan, Scott

    2016-01-01

    This paper will describe the technology development efforts NASA has underway for Automated Rendezvous and Docking/Capture (AR&D/C) sensors and a docking mechanism and the challenges involved. The paper will additionally address how these technologies will be extended to other missions requiring AR&D/C whether robotic or manned. NASA needs AR&D/C sensors for both the robotic and crewed segments of the Asteroid Redirect Mission (ARM). NASA recently conducted a commonality assessment of the concept of operations for the robotic Asteroid Redirect Vehicle (ARV) and the crewed mission segment using the Orion spacecraft. The commonality assessment also considered several future exploration and science missions requiring an AR&D/C capability. Missions considered were asteroid sample return, satellite servicing, and planetary entry, descent, and landing. This assessment determined that a common sensor suite consisting of one or more visible wavelength cameras, a three-dimensional LIDAR along with long-wavelength infrared cameras for robustness and situational awareness could be used on each mission to eliminate the cost of multiple sensor developments and qualifications. By choosing sensor parameters at build-time instead of at design-time and, without having to requalify flight hardware, a specific mission can design overlapping bearing, range, relative attitude, and position measurement availability to suit their mission requirements with minimal non-recurring engineering costs. The resulting common sensor specification provides the union of all performance requirements for each mission and represents an improvement over the current systems used for AR&D/C today. These sensor specifications are tightly coupled to the docking system capabilities and requirements for final docking conditions. The paper will describe NASA's efforts to develop a standard docking system for use across NASA human spaceflight missions to multiple destinations. It will describe the current

  20. Molecular Recognition Analyzed by Docking Simulations: The Aspartate Receptor and Isocitrate Dehydrogenase from Escherichia coli

    Science.gov (United States)

    Stoddard, Barry L.; Koshland, Daniel E., Jr.

    1993-02-01

    Protein docking protocols are used for the prediction of both small molecule binding to DNA and protein macromolecules and of complexes between macromolecules. These protocols are becoming increasingly automated and powerful tools for computer-aided drug design. We review the basic methodologies and strategies used for analyzing molecular recognition by computer docking algorithms and discuss recent experiments in which (i) substrate and substrate analogues are docked to the active site of isocitrate dehydrogenase and (ii) maltose binding protein is docked to the extracellular domain of the receptor, which signals maltose chemotaxis.

  1. Autonomous spacecraft rendezvous and docking

    Science.gov (United States)

    Tietz, J. C.; Almand, B. J.

    A storyboard display is presented which summarizes work done recently in design and simulation of autonomous video rendezvous and docking systems for spacecraft. This display includes: photographs of the simulation hardware, plots of chase vehicle trajectories from simulations, pictures of the docking aid including image processing interpretations, and drawings of the control system strategy. Viewgraph-style sheets on the display bulletin board summarize the simulation objectives, benefits, special considerations, approach, and results.

  2. I-AUV Docking and Panel Intervention at Sea

    Directory of Open Access Journals (Sweden)

    Narcís Palomeras

    2016-10-01

    Full Text Available The use of commercially available autonomous underwater vehicles (AUVs has increased during the last fifteen years. While they are mainly used for routine survey missions, there is a set of applications that nowadays can be only addressed by manned submersibles or work-class remotely operated vehicles (ROVs equipped with teleoperated arms: the intervention applications. To allow these heavy vehicles controlled by human operators to perform intervention tasks, underwater structures like observatory facilities, subsea panels or oil-well Christmas trees have been adapted, making them more robust and easier to operate. The TRITON Spanish founded project proposes the use of a light-weight intervention AUV (I-AUV to carry out intervention applications simplifying the adaptation of these underwater structures and drastically reducing the operational cost. To prove this concept, the Girona 500 I-AUV is used to autonomously dock into an adapted subsea panel and once docked perform an intervention composed of turning a valve and plugging in/unplugging a connector. The techniques used for the autonomous docking and manipulation as well as the design of an adapted subsea panel with a funnel-based docking system are presented in this article together with the results achieved in a water tank and at sea.

  3. The focal adhesion-associated proteins DOCK5 and GIT2 comprise a rheostat in control of epithelial invasion

    DEFF Research Database (Denmark)

    Frank, S R; Köllmann, C P; van Lidth de Jeude, J F;

    2017-01-01

    DOCK proteins are guanine nucleotide exchange factors for Rac and Cdc42 GTPases. DOCK1 is the founding member of the family and acts downstream of integrins via the canonical Crk-p130Cas complex to activate Rac GTPases in numerous contexts. In contrast, DOCK5, which possesses the greatest...... with these cells. Collectively, our work identifies DOCK5 as a key regulator of epithelial invasion and metastasis, and demonstrates that suppression of DOCK5 by GIT2 represents a previously unappreciated mechanism for coordination of Rho and Rac GTPases.Oncogene advance online publication, 26 September 2016; doi...

  4. Uranyl complexes formed with a para-t-butylcalix[4]arene bearing phosphinoyl pendant arms on the lower rim. Solid and solution studies

    Energy Technology Data Exchange (ETDEWEB)

    Ramirez, F. de M. [Instituto Nacional de Investigaciones Nucleares, La Marquesa, Ocoyoacac (Mexico). Dept. de Quimica; Varbanov, S. [Bulgarian Academy of Sciences, Sofia (Bulgaria). Inst. of Organic Chemistry with Center of Phytochemistry; Buenzli, J.C.G. [Ecole Polytechnique Federale de Lausanne (EPFL) (Switzerland). Inst. of Chemical Sciences and Engineering; Rivas-Silva, J.F.; Ocana-Bribiesca, M.A. [Instituto de Fisica de la BUAP, Puebla (Mexico); Cortes-Jacome, M.A.; Toledo-Antonio, J.A. [Instituto Mexicano del Petroleo/Programa de Ingenieria Molecular (Mexico)

    2012-07-01

    The current interest in functionalized calixarenes with phosphorylated pendant arms resides in their coordination ability towards f elements and capability towards actinide/rare earth separation. Uranyl cation forms 1:1 and 1:2 (M:L) complexes with a tetra-phosphinoylated p-tert-butylcalix[4]arene, B{sub 4}bL{sup 4}: UO{sub 2}(NO{sub 3}){sub 2}(B{sub 4}bL{sup 4}){sub n} . xH{sub 2}O (n = 1, x = 2, 1; n = 2, x = 6, 2). Spectroscopic data point to the inner coordination sphere of 1 containing one monodentate nitrate anion, one water molecule and the four phosphinoylated arms bound to UO{sub 2}{sup 2+} while in 2, uranyl is only coordinated to calixarene ligands. In both cases the U(VI) ion is 8-coordinate. Uranyl complexes display enhanced metal-centred luminescence due to energy transfer from the calixarene ligands; the luminescence decays are bi-exponential with associated lifetimes in the ranges 220 {mu}s < {tau}{sub s} < 250 {mu}s and 630 {mu}s < {tau}{sub L} < 640 {mu}s, pointing to the presence of two species with differently coordinated calixarene, as substantiated by a XPS study of U(4f{sub 5/2,7/2}), O(1s) and P(2p) levels on solid state samples. The extraction study of UO{sub 2}{sup 2+} cation and trivalent rare-earth (Y, La, Eu) ions from acidic nitrate media by B{sub 4}bL{sup 4} in chloroform shows the uranyl cation being much more extracted than rare earths. (orig.)

  5. Calcium carbene complexes with boranophosphorano side-arms: CaC[P(Ph)(2)BH(3)](2).

    Science.gov (United States)

    Orzechowski, Lars; Jansen, Georg; Lutz, Martin; Harder, Sjoerd

    2009-04-28

    The ligand H(2)C(PPh(2)BH(3))(2) (-H(2)) reacted with one or a half equivalent of (para-tBu-C(6)H(4)CH(2))(2)Ca.(THF)(4) to form the calcium complexes Ca[HC(PPh(2)BH(3))(2)](2) (-H)(2)Ca and CaC(PPh(2)BH(3))(2) (-Ca), respectively. The crystal structures of their THF adducts (-H)(2)Ca.THF and [-Ca.(THF)](2) follow the same trends as observed for the corresponding iminophosphorano substituted complexes Ca[HC(PPh(2)NR)(2)](2) and [CaC(PPh(2)NR)(2)](2). The P-C bonds shorten upon gradual deprotonation, whereas the P-B and P-N bonds elongate. The geometries of DFT-optimized model systems and complete molecular structures show similar trends. Also the charge distribution within the boranophosphorano complexes is similar to that in the iminophosphorano complexes. The high positive charges on Ca (1.74-1.75) indicate a predominantly ionic ligand-Ca bonding. High negative charges on the central carbon atom (-1.103 in Ca[HC(PH(2)BH(3))(2)](2) and -1.775 in [CaC(PH(2)BH(3))(2)](2)) compare well to those calculated for analogous iminophosphorano complexes (-1.126 Ca[HC(PH(2)NH)(2)](2) and -1.847 [CaC(PH(2)NH)(2)](2), respectively). Thus, in both types of complexes delocalization of electron density over the boranophosphorano or iminophosphorano substituents does not play a major role. Complex [-Ca.(THF)](2) does not react with adamantyl cyanide. Instead the adduct (-Ca)(2).(THF).(adamantyl-C[triple bond, length as m-dash]N) formed (a crystal structure has been determined).

  6. Effects of protein conformation in docking: improved pose prediction through protein pocket adaptation.

    Science.gov (United States)

    Jain, Ajay N

    2009-06-01

    Computational methods for docking ligands have been shown to be remarkably dependent on precise protein conformation, where acceptable results in pose prediction have been generally possible only in the artificial case of re-docking a ligand into a protein binding site whose conformation was determined in the presence of the same ligand (the "cognate" docking problem). In such cases, on well curated protein/ligand complexes, accurate dockings can be returned as top-scoring over 75% of the time using tools such as Surflex-Dock. A critical application of docking in modeling for lead optimization requires accurate pose prediction for novel ligands, ranging from simple synthetic analogs to very different molecular scaffolds. Typical results for widely used programs in the "cross-docking case" (making use of a single fixed protein conformation) have rates closer to 20% success. By making use of protein conformations from multiple complexes, Surflex-Dock yields an average success rate of 61% across eight pharmaceutically relevant targets. Following docking, protein pocket adaptation and rescoring identifies single pose families that are correct an average of 67% of the time. Consideration of the best of two pose families (from alternate scoring regimes) yields a 75% mean success rate.

  7. Docking of B-cell epitope antigen to specific hepatitis B antibody

    Indian Academy of Sciences (India)

    R Rajkannan; E J Padma Malar

    2007-09-01

    The interaction of pres1 region of hepatitis B virus B-cell epitope antigen with specific hepatitis B neutralizing monoclonal antibody was examined by docking study. We modelled the 3D complex structure of B-cell epitope antigen residues CTTPAQGNSMFPSCCCTKPTDGNCY by homology modelling and docked it with the crystal structure of monoclonal antibody specific for the pres1 region of the hepatitis B virus. At the optimized docked conformation, the interactions between the amino acids of antigen and antibody were examined. It is found that the docked complex is stabilized by 59.3 kcal/mol. The stability of the docked antigen-antibody complex is due to hydrogen bonding and van der Waals interactions. The amino acids of the antigen and antibody responsible for the interaction were identified.

  8. Molecular docking and molecular dynamics simulation study of inositol phosphorylceramide synthase – inhibitor complex in leishmaniasis: Insight into the structure based drug design [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Vineetha Mandlik

    2016-09-01

    Full Text Available Inositol phosphorylceramide synthase (IPCS has emerged as an important, interesting and attractive target in the sphingolipid metabolism of Leishmania. IPCS catalyzes the conversion of ceramide to IPC which forms the most predominant sphingolipid in Leishmania. IPCS has no mammalian equivalent and also plays an important role in maintaining the infectivity and viability of the parasite. The present study explores the possibility of targeting IPCS; development of suitable inhibitors for the same would serve as a treatment strategy for the infectious disease leishmaniasis. Five coumarin derivatives were developed as inhibitors of IPCS protein. Molecular dynamics simulations of the complexes of IPCS with these inhibitors were performed which provided insights into the binding modes of the inhibitors. In vitro screening of the top three compounds has resulted in the identification of one of the compounds (compound 3 which shows little cytotoxic effects. This compound therefore represents a good starting point for further in vivo experimentation and could possibly serve as an important drug candidate for the treatment of leishmaniasis.

  9. Late steps in cytoplasmic maturation of assembly-competent axonemal outer arm dynein in Chlamydomonas require interaction of ODA5 and ODA10 in a complex.

    Science.gov (United States)

    Dean, Anudariya B; Mitchell, David R

    2015-10-15

    Axonemal dyneins are multisubunit enzymes that must be preassembled in the cytoplasm, transported into cilia by intraflagellar transport, and bound to specific sites on doublet microtubules, where their activity facilitates microtubule sliding-based motility. Outer dynein arms (ODAs) require assembly factors to assist their preassembly, transport, and attachment to cargo (specific doublet A-tubule sites). In Chlamydomonas, three assembly factors--ODA5, ODA8, and ODA10--show genetic interactions and have been proposed to interact in a complex, but we recently showed that flagellar ODA8 does not copurify with ODA5 or ODA10. Here we show that ODA5 and ODA10 depend on each other for stability and coexist in a complex in both cytoplasmic and flagellar extracts. Immunofluorescence and immuno-electron microscopy reveal that ODA10 in flagella localizes strictly to a proximal region of doublet number 1, which completely lacks ODAs in Chlamydomonas. Studies of the in vitro binding of ODAs to axonemal doublets reveal a role for the ODA5/ODA10 assembly complex in cytoplasmic maturation of ODAs into a form that can bind to doublet microtubules.

  10. A Study on Spectro-Analytical Aspects, DNA - Interaction, Photo-Cleavage, Radical Scavenging, Cytotoxic Activities, Antibacterial and Docking Properties of 3 - (1 - (6 - methoxybenzo [d] thiazol - 2 - ylimino) ethyl) - 6 - methyl - 3H - pyran - 2, 4 - dione and its Metal Complexes.

    Science.gov (United States)

    Ravi, Mudavath; Chennam, Kishan Prasad; Ushaiah, B; Eslavath, Ravi Kumar; Perugu, Shyam; Ajumeera, Rajanna; Devi, Ch Sarala

    2015-09-01

    The focus of the present work is on the design, synthesis, characterization, DNA-interaction, photo-cleavage, radical scavenging, in-vitro cytotoxicity, antimicrobial, docking and kinetic studies of Cu (II), Cd (II), Ce (IV) and Zr (IV) metal complexes of an imine derivative, 3 - (1 - (6 - methoxybenzo [d] thiazol - 2 - ylimino) ethyl) - 6 - methyl - 3H - pyran - 2, 4 - dione. The investigation of metal ligand interactions for the determination of composition of metal complexes, corresponding kinetic studies and antioxidant activity in solution was carried out by spectrophotometric methods. The synthesized metal complexes were characterized by EDX analysis, Mass, IR, (1)H-NMR, (13)C-NMR and UV-Visible spectra. DNA binding studies of metal complexes with Calf thymus (CT) DNA were carried out at room temperature by employing UV-Vis electron absorption, fluorescence emission and viscosity measurement techniques. The results revealed that these complexes interact with DNA through intercalation. The results of in vitro antibacterial studies showed the enhanced activity of chelating agent in metal chelated form and thus inferring scope for further development of new therapeutic drugs. Cell viability experiments indicated that all complexes showed significant dose dependent cytotoxicity in selected cell lines. The molecular modeling and docking studies were carried out with energy minimized structures of metal complexes to identify the receptor to metal interactions.

  11. Combining docking and molecular dynamic simulations in drug design.

    Science.gov (United States)

    Alonso, Hernán; Bliznyuk, Andrey A; Gready, Jill E

    2006-09-01

    A rational approach is needed to maximize the chances of finding new drugs, and to exploit the opportunities of potential new drug targets emerging from genomic and proteomic initiatives, and from the large libraries of small compounds now readily available through combinatorial chemistry. Despite a shaky early history, computer-aided drug design techniques can now be effective in reducing costs and speeding up drug discovery. This happy outcome results from development of more accurate and reliable algorithms, use of more thoughtfully planned strategies to apply them, and greatly increased computer power to allow studies with the necessary reliability to be performed. Our review focuses on applications and protocols, with the main emphasis on critical analysis of recent studies where docking calculations and molecular dynamics (MD) simulations were combined to dock small molecules into protein receptors. We highlight successes to demonstrate what is possible now, but also point out drawbacks and future directions. The review is structured to lead the reader from the simpler to more compute-intensive methods. Thus, while inexpensive and fast docking algorithms can be used to scan large compound libraries and reduce their size, more accurate but expensive MD simulations can be applied when a few selected ligand candidates remain. MD simulations can be used: during the preparation of the protein receptor before docking, to optimize its structure and account for protein flexibility; for the refinement of docked complexes, to include solvent effects and account for induced fit; to calculate binding free energies, to provide an accurate ranking of the potential ligands; and in the latest developments, during the docking process itself to find the binding site and correctly dock the ligand a priori.

  12. Molecular docking and structure-based drug design strategies.

    Science.gov (United States)

    Ferreira, Leonardo G; Dos Santos, Ricardo N; Oliva, Glaucius; Andricopulo, Adriano D

    2015-07-22

    Pharmaceutical research has successfully incorporated a wealth of molecular modeling methods, within a variety of drug discovery programs, to study complex biological and chemical systems. The integration of computational and experimental strategies has been of great value in the identification and development of novel promising compounds. Broadly used in modern drug design, molecular docking methods explore the ligand conformations adopted within the binding sites of macromolecular targets. This approach also estimates the ligand-receptor binding free energy by evaluating critical phenomena involved in the intermolecular recognition process. Today, as a variety of docking algorithms are available, an understanding of the advantages and limitations of each method is of fundamental importance in the development of effective strategies and the generation of relevant results. The purpose of this review is to examine current molecular docking strategies used in drug discovery and medicinal chemistry, exploring the advances in the field and the role played by the integration of structure- and ligand-based methods.

  13. Docking of Secretory Vesicles Is Syntaxin Dependent

    Science.gov (United States)

    de Wit, Heidi; Cornelisse, L. Niels; Toonen, Ruud F.G.; Verhage, Matthijs

    2006-01-01

    Secretory vesicles dock at the plasma membrane before they undergo fusion. Molecular docking mechanisms are poorly defined but believed to be independent of SNARE proteins. Here, we challenged this hypothesis by acute deletion of the target SNARE, syntaxin, in vertebrate neurons and neuroendocrine cells. Deletion resulted in fusion arrest in both systems. No docking defects were observed in synapses, in line with previous observations. However, a drastic reduction in morphologically docked secretory vesicles was observed in chromaffin cells. Syntaxin-deficient chromaffin cells showed a small reduction in total and plasma membrane staining for the docking factor Munc18-1, which appears insufficient to explain the drastic reduction in docking. The sub-membrane cortical actin network was unaffected by syntaxin deletion. These observations expose a docking role for syntaxin in the neuroendocrine system. Additional layers of regulation may have evolved to make syntaxin redundant for docking in highly specialized systems like synaptic active zones. PMID:17205130

  14. Docking of secretory vesicles is syntaxin dependent.

    Directory of Open Access Journals (Sweden)

    Heidi de Wit

    Full Text Available Secretory vesicles dock at the plasma membrane before they undergo fusion. Molecular docking mechanisms are poorly defined but believed to be independent of SNARE proteins. Here, we challenged this hypothesis by acute deletion of the target SNARE, syntaxin, in vertebrate neurons and neuroendocrine cells. Deletion resulted in fusion arrest in both systems. No docking defects were observed in synapses, in line with previous observations. However, a drastic reduction in morphologically docked secretory vesicles was observed in chromaffin cells. Syntaxin-deficient chromaffin cells showed a small reduction in total and plasma membrane staining for the docking factor Munc18-1, which appears insufficient to explain the drastic reduction in docking. The sub-membrane cortical actin network was unaffected by syntaxin deletion. These observations expose a docking role for syntaxin in the neuroendocrine system. Additional layers of regulation may have evolved to make syntaxin redundant for docking in highly specialized systems like synaptic active zones.

  15. Influence of terminal acryloyl arms on the coordination chemistry of a ditopic pyrimidine-hydrazone ligand: comparison of Pb(II), Zn(II), Cu(II), and Ag(I) complexes.

    Science.gov (United States)

    Hutchinson, Daniel J; Hanton, Lyall R; Moratti, Stephen C

    2013-03-01

    A new ditopic pyrimidine-hydrazone ligand, 6-hydroxymethylacryloyl-2-pyridinecarboxaldehyde, 2,2'-[2,2'-(2-methyl-4,6-pyrimidinediyl)bis(1-methylhydrazone)] (L2), was synthesized with terminal acryloyl functional groups to allow incorporation into copolymer gel actuators. NMR spectroscopy was used to show that L2 adopted a horseshoe shape with transoid-transoid pym-hyz-py linkages. Metal complexation studies were performed with L2 and salts of Pb(II), Zn(II), Cu(II), and Ag(I) ions in CH3CN in a variety of metal to ligand ratios. Reacting L2 with an excess amount of any of the metal ions resulted in linear complexes where the pym-hyz-py linkages were rotated to a cisoid-cisoid conformation. NMR spectroscopy showed that the acryloyl arms of L2 did not interact with the bound metal ions in solution. Seven of the linear complexes (1-7) were crystallized and analyzed by X-ray diffraction. Most of these complexes (4-7) also showed no coordination between the acryloyl arms and the metal ions; however, complexes 1-3 showed some interactions. Both of the acryloyl arms were coordinated to Pb(II) ions in [Pb2L2(SO3CF3)4] (1), one through the carbonyl oxygen donor and the other through the alkoxy oxygen donor. One of the acryloyl arms of [Cu2L2(CH3CN)3](SO3CF3)4 (2) was coordinated to one of the Cu(II) ions through the carbonyl oxygen donor. There appeared to be a weak association between the alkoxy donors of the acryloyl arms and the Pb(II) ions of [Pb2L2(ClO4)4]·CH3CN (3). Reaction of excess AgSO3CF3 with L2 was repeated in CD3NO2, resulting in crystals of {[Ag7(L2)2(SO3CF3)6(H2O)2] SO3CF3}∞ (8), the polymeric structure of which resulted from coordination between the carbonyl donors of the acryloyl arms and the Ag(I) ions. In all cases the coordination and steric effects of the acryloyl arms did not inhibit isomerization of the pym-hyz bonds of L2 or the core shape of the linear complexes.

  16. Gene knockout using transcription activator-like effector nucleases (TALENs) reveals that human NDUFA9 protein is essential for stabilizing the junction between membrane and matrix arms of complex I.

    Science.gov (United States)

    Stroud, David A; Formosa, Luke E; Wijeyeratne, Xiaonan W; Nguyen, Thanh N; Ryan, Michael T

    2013-01-18

    Transcription activator-like effector nucleases (TALENs) represent a promising approach for targeted knock-out of genes in cultured human cells. We used TALEN-technology to knock out the nuclear gene encoding NDUFA9, a subunit of mitochondrial respiratory chain complex I in HEK293T cells. Screening for the knock-out revealed a mixture of NDUFA9 cell clones that harbored partial deletions of the mitochondrial N-terminal targeting signal but were still capable of import. A cell line lacking functional copies of both NDUFA9 alleles resulted in a loss of NDUFA9 protein expression, impaired assembly of complex I, and cells incapable of growth in galactose medium. Cells lacking NDUFA9 contained a complex I subcomplex consisting of membrane arm subunits but not marker subunits of the matrix arm. Re-expression of NDUFA9 restored the defects in complex I assembly. We conclude that NDUFA9 is involved in stabilizing the junction between membrane and matrix arms of complex I, a late assembly step critical for complex I biogenesis and activity.

  17. Three-way complex variant translocation involving short arm chromosome (1;9;22)(p36;q34;q11) in a chronic myeloid leukemia patient

    Science.gov (United States)

    ASIF, MUHAMMAD; HUSSAIN, ABRAR; MALIK, ARIF; RASOOL, MAHMOOD

    2015-01-01

    Chronic myeloid leukemia (CML) is a disease of the clonal hematopoietic stem cells caused by a balanced translocation between the long arms of chromosomes 9 and 22. Overall, 90–95% of CML patients present with a Philadelphia (Ph) chromosome t(9;22)(q34;q11) translocation and in addition, variant complex translocations, involving a third chromosome, are observed in 5–8% of CML patients. Cytogenic testing using bone marrow sample was performed and the FISH test was used for the detection of BCR-ABL fusion gene and complete blood analysis of CML patient was also performed. Results of hematological analysis showed the induced values of white blood cells (168,5000/mm3) and platelets (300,000/mm3) and FISH analysis test showed that 98% cells were positive for BCR/ABL gene translocation. The present study describes a three-way (1;9;22)(p36;q34;q11) Ph chromosome translocation in a 24-year-old female with CML. The patient, who was in the chronic phase of the disease, was treated with daily dose of 400 mg/dl with imatinib mesylateand was monitored constantly at various intervals over a 6-month period. Many studies reported that certain CML patents with variant translocation responded poorly to imatinib. In the current case report, the CML patient exhibited a suboptimal response to imatinib, denoting a poor prognosis. PMID:26622740

  18. Complejidad, conflicto armado y vulnerabilidad de niños y niñas desplazados en colombia (complexity, armed conflict, and vulnerability of displaced children in colombia

    Directory of Open Access Journals (Sweden)

    Jose Alonso Andrade Salazar

    2014-12-01

    Full Text Available RESUMEN: Este trabajo tiene como objetivo realizar una reflexión acerca de la vulnerabilidad de los niños y niñas víctimas del conflicto armado en Colombia. Para ello se recurriro al principio de auto-eco-organización y de Bucle inter-retroactivo. La violencia es un fenómeno complejo de múltiples interacciones, de características no-lineales y tendencia auto-eo-organizativa que afecta la noción de sujeto y altera el modo como los niños y niñas interpretan el mundo y sus interacciones. ABSTRACT: This paper aims to carry out a reflection on the vulnerability of children, who are victims of the armed conflict in Colombia. This was used at the beginning of the self-eco-organization and the inter-retroactive loop. Violence is a complex phenomenon of multiple interactions, non-linear features, and a self-ecoorganizational tendency, which affects the notion of subject and alters the way that children interpret the world and their interactions.

  19. Evaluation of the coarse-grained OPEP force field for protein-protein docking

    OpenAIRE

    Kynast, Philipp; Derreumaux, Philippe; Strodel, Birgit

    2016-01-01

    International audience; Background: Knowing the binding site of protein–protein complexes helps understand their function and shows possible regulation sites. The ultimate goal of protein–protein docking is the prediction of the three-dimensional structure of a protein–protein complex. Docking itself only produces plausible candidate structures, which must be ranked using scoring functions to identify the structures that are most likely to occur in nature. Methods: In this work, we rescore ri...

  20. A fast flexible docking method using an incremental construction algorithm.

    Science.gov (United States)

    Rarey, M; Kramer, B; Lengauer, T; Klebe, G

    1996-08-23

    We present an automatic method for docking organic ligands into protein binding sites. The method can be used in the design process of specific protein ligands. It combines an appropriate model of the physico-chemical properties of the docked molecules with efficient methods for sampling the conformational space of the ligand. If the ligand is flexible, it can adopt a large variety of different conformations. Each such minimum in conformational space presents a potential candidate for the conformation of the ligand in the complexed state. Our docking method samples the conformation space of the ligand on the basis of a discrete model and uses a tree-search technique for placing the ligand incrementally into the active site. For placing the first fragment of the ligand into the protein, we use hashing techniques adapted from computer vision. The incremental construction algorithm is based on a greedy strategy combined with efficient methods for overlap detection and for the search of new interactions. We present results on 19 complexes of which the binding geometry has been crystallographically determined. All considered ligands are docked in at most three minutes on a current workstation. The experimentally observed binding mode of the ligand is reproduced with 0.5 to 1.2 A rms deviation. It is almost always found among the highest-ranking conformations computed.

  1. Simulation of carbohydrates, from molecular docking to dynamics in water.

    Science.gov (United States)

    Sapay, Nicolas; Nurisso, Alessandra; Imberty, Anne

    2013-01-01

    Modeling of carbohydrates is particularly challenging because of the variety of structures resulting for the high number of monosaccharides and possible linkages and also because of their intrinsic flexibility. The development of carbohydrate parameters for molecular modeling is still an active field. Nowadays, main carbohydrates force fields are GLYCAM06, CHARMM36, and GROMOS 45A4. GLYCAM06 includes the largest choice of compounds and is compatible with the AMBER force fields and associated. Furthermore, AMBER includes tools for the implementation of new parameters. When looking at protein-carbohydrate interaction, the choice of the starting structure is of importance. Such complex can be sometimes obtained from the Protein Data Bank-although the stereochemistry of sugars may require some corrections. When no experimental data is available, molecular docking simulation is generally used to the obtain protein-carbohydrate complex coordinates. As molecular docking parameters are not specifically dedicated to carbohydrates, inaccuracies should be expected, especially for the docking of polysaccharides. This issue can be addressed at least partially by combining molecular docking with molecular dynamics simulation in water.

  2. PSOVina: The hybrid particle swarm optimization algorithm for protein-ligand docking.

    Science.gov (United States)

    Ng, Marcus C K; Fong, Simon; Siu, Shirley W I

    2015-06-01

    Protein-ligand docking is an essential step in modern drug discovery process. The challenge here is to accurately predict and efficiently optimize the position and orientation of ligands in the binding pocket of a target protein. In this paper, we present a new method called PSOVina which combined the particle swarm optimization (PSO) algorithm with the efficient Broyden-Fletcher-Goldfarb-Shannon (BFGS) local search method adopted in AutoDock Vina to tackle the conformational search problem in docking. Using a diverse data set of 201 protein-ligand complexes from the PDBbind database and a full set of ligands and decoys for four representative targets from the directory of useful decoys (DUD) virtual screening data set, we assessed the docking performance of PSOVina in comparison to the original Vina program. Our results showed that PSOVina achieves a remarkable execution time reduction of 51-60% without compromising the prediction accuracies in the docking and virtual screening experiments. This improvement in time efficiency makes PSOVina a better choice of a docking tool in large-scale protein-ligand docking applications. Our work lays the foundation for the future development of swarm-based algorithms in molecular docking programs. PSOVina is freely available to non-commercial users at http://cbbio.cis.umac.mo .

  3. A COMPLEX ADAPTIVE STATE SYSTEM: NETWORKS, ARMS RACES AND MORAL HAZARDS Un sistema adaptativo complejo: Redes, carreras armamentistas y peligros morales

    Directory of Open Access Journals (Sweden)

    PABLO POLICZER

    2012-01-01

    Full Text Available Much of the debate over stateness in Latin America assumes that states should sustain basic levels of stability, and if they cannot, the question is why not. This article departs from the assumption of stability, by asking how the relationship between states and other actors has evolved over time. This departure requires a shift in focus: from stateness as referring to states and how they should operate, to stateness as referring to the relationships between states and other actors, and how they change over time. The article argues that such relationships can be understood as emergent complex adaptive systems (CAS, and considers three specific CAS mechanisms: networks, arms races, and moral hazards. This conceptual shift in how to think about states is especially challenging in a region historically accustomed to hierarchical governance.Buena parte del debate sobre la estatalidad en América Latina presupone que los estados deben mantener niveles básicos de estabilidad, y que si no pueden hacerlo, la pregunta es por qué no. Este artículo se aleja del supuesto de la estabilidad, al preguntar cómo la relación entre los estados y otros actores ha evolucionado con el tiempo. Esto requiere un cambio de enfoque: de estatalidad que se refiere a los estados y cómo debieran funcionar, a la estatalidad en referencia a las relaciones entre los estados y otros actores, y cómo éstas cambian con el tiempo. El artículo sostiene que este tipo de relaciones se puede entender como sistemas complejos adaptativos (SCA emergentes, y considera tres mecanismos específicos de SCA: redes, carreras armamentistas y peligros morales (moral hazards. Este cambio conceptual en laforma de pensar acerca de los estados es especialmente difícil en una región históricamente acostumbrada a la gobernanza jerárquica.

  4. Predicting the structures of complexes between phosphoinositide 3-kinase (PI3K) and romidepsin-related compounds for the drug design of PI3K/histone deacetylase dual inhibitors using computational docking and the ligand-based drug design approach.

    Science.gov (United States)

    Oda, Akifumi; Saijo, Ken; Ishioka, Chikashi; Narita, Koichi; Katoh, Tadashi; Watanabe, Yurie; Fukuyoshi, Shuichi; Takahashi, Ohgi

    2014-11-01

    Predictions of the three-dimensional (3D) structures of the complexes between phosphoinositide 3-kinase (PI3K) and two inhibitors were conducted using computational docking and the ligand-based drug design approach. The obtained structures were refined by structural optimizations and molecular dynamics (MD) simulations. The ligands were located deep inside the ligand binding pocket of the p110α subunit of PI3K, and the hydrogen bond formations and hydrophobic effects of the surrounding amino acids were predicted. Although rough structures were obtained for the PI3K-inhibitor complexes before the MD simulations, the refinement of the structures by these simulations clarified the hydrogen bonding patterns of the complexes.

  5. PaFlexPepDock: parallel ab-initio docking of peptides onto their receptors with full flexibility based on Rosetta.

    Directory of Open Access Journals (Sweden)

    Haiou Li

    Full Text Available Structural information related to protein-peptide complexes can be very useful for novel drug discovery and design. The computational docking of protein and peptide can supplement the structural information available on protein-peptide interactions explored by experimental ways. Protein-peptide docking of this paper can be described as three processes that occur in parallel: ab-initio peptide folding, peptide docking with its receptor, and refinement of some flexible areas of the receptor as the peptide is approaching. Several existing methods have been used to sample the degrees of freedom in the three processes, which are usually triggered in an organized sequential scheme. In this paper, we proposed a parallel approach that combines all the three processes during the docking of a folding peptide with a flexible receptor. This approach mimics the actual protein-peptide docking process in parallel way, and is expected to deliver better performance than sequential approaches. We used 22 unbound protein-peptide docking examples to evaluate our method. Our analysis of the results showed that the explicit refinement of the flexible areas of the receptor facilitated more accurate modeling of the interfaces of the complexes, while combining all of the moves in parallel helped the constructing of energy funnels for predictions.

  6. DrugScorePPI knowledge-based potentials used as scoring and objective function in protein-protein docking.

    Directory of Open Access Journals (Sweden)

    Dennis M Krüger

    Full Text Available The distance-dependent knowledge-based DrugScore(PPI potentials, previously developed for in silico alanine scanning and hot spot prediction on given structures of protein-protein complexes, are evaluated as a scoring and objective function for the structure prediction of protein-protein complexes. When applied for ranking "unbound perturbation" ("unbound docking" decoys generated by Baker and coworkers a 4-fold (1.5-fold enrichment of acceptable docking solutions in the top ranks compared to a random selection is found. When applied as an objective function in FRODOCK for bound protein-protein docking on 97 complexes of the ZDOCK benchmark 3.0, DrugScore(PPI/FRODOCK finds up to 10% (15% more high accuracy solutions in the top 1 (top 10 predictions than the original FRODOCK implementation. When used as an objective function for global unbound protein-protein docking, fair docking success rates are obtained, which improve by ∼ 2-fold to 18% (58% for an at least acceptable solution in the top 10 (top 100 predictions when performing knowledge-driven unbound docking. This suggests that DrugScore(PPI balances well several different types of interactions important for protein-protein recognition. The results are discussed in view of the influence of crystal packing and the type of protein-protein complex docked. Finally, a simple criterion is provided with which to estimate a priori if unbound docking with DrugScore(PPI/FRODOCK will be successful.

  7. Ligand-protein docking using a quantum stochastic tunneling optimization method.

    Science.gov (United States)

    Mancera, Ricardo L; Källblad, Per; Todorov, Nikolay P

    2004-04-30

    A novel hybrid optimization method called quantum stochastic tunneling has been recently introduced. Here, we report its implementation within a new docking program called EasyDock and a validation with the CCDC/Astex data set of ligand-protein complexes using the PLP score to represent the ligand-protein potential energy surface and ScreenScore to score the ligand-protein binding energies. When taking the top energy-ranked ligand binding mode pose, we were able to predict the correct crystallographic ligand binding mode in up to 75% of the cases. By using this novel optimization method run times for typical docking simulations are significantly shortened.

  8. Dimerization of DOCK2 is essential for DOCK2-mediated Rac activation and lymphocyte migration.

    Directory of Open Access Journals (Sweden)

    Masao Terasawa

    Full Text Available The migratory properties of lymphocytes depend on DOCK2, an atypical Rac activator predominantly expressed in hematopoietic cells. Although DOCK2 does not contain the Dbl homology domain typically found in guanine nucleotide exchange factors (GEFs, DOCK2 mediates the GTP-GDP exchange reaction for Rac via its DOCK homology region (DHR-2 (also known as CZH2 or Docker domain. DOCK2 DHR-2 domain is composed of three lobes, and Rac binding site and catalytic center are generated entirely from lobes B and C. On the other hand, lobe A has been implicated in dimer formation, yet its physiological significance remains unknown. Here, we report that lobe A-mediated DOCK2 dimerization is crucial for Rac activation and lymphocyte migration. We found that unlike wild-type DOCK2, DOCK2 mutant lacking lobe A failed to restore motility and polarity when expressed in thymoma cells and primary T cells lacking endogenous expression of DOCK2. Similar results were obtained with the DOCK2 point mutant having a defect in dimerization. Deletion of lobe A from the DHR-2 domain did not affect Rac GEF activity in vitro. However, fluorescence resonance energy transfer analyses revealed that lobe A is required for DOCK2 to activate Rac effectively during cell migration. Our results thus indicate that DOCK2 dimerization is functionally important under the physiological condition where only limited amounts of DOCK2 and Rac are localized to the plasma membrane.

  9. Introduction to Reading and Visualizing ARM Data

    Energy Technology Data Exchange (ETDEWEB)

    Mather, James [Pacific Northwest National Laboratory

    2014-02-18

    Atmospheric Radiation Measurement (ARM) Program standard data format is NetCDF 3 (Network Common Data Form). The object of this tutorial is to provide a basic introduction to NetCDF with an emphasis on aspects of the ARM application of NetCDF. The goal is to provide basic instructions for reading and visualizing ARM NetCDF data with the expectation that these examples can then be applied to more complex applications.

  10. Protein-protein docking using region-based 3D Zernike descriptors

    Directory of Open Access Journals (Sweden)

    Sael Lee

    2009-12-01

    Full Text Available Abstract Background Protein-protein interactions are a pivotal component of many biological processes and mediate a variety of functions. Knowing the tertiary structure of a protein complex is therefore essential for understanding the interaction mechanism. However, experimental techniques to solve the structure of the complex are often found to be difficult. To this end, computational protein-protein docking approaches can provide a useful alternative to address this issue. Prediction of docking conformations relies on methods that effectively capture shape features of the participating proteins while giving due consideration to conformational changes that may occur. Results We present a novel protein docking algorithm based on the use of 3D Zernike descriptors as regional features of molecular shape. The key motivation of using these descriptors is their invariance to transformation, in addition to a compact representation of local surface shape characteristics. Docking decoys are generated using geometric hashing, which are then ranked by a scoring function that incorporates a buried surface area and a novel geometric complementarity term based on normals associated with the 3D Zernike shape description. Our docking algorithm was tested on both bound and unbound cases in the ZDOCK benchmark 2.0 dataset. In 74% of the bound docking predictions, our method was able to find a near-native solution (interface C-αRMSD ≤ 2.5 Å within the top 1000 ranks. For unbound docking, among the 60 complexes for which our algorithm returned at least one hit, 60% of the cases were ranked within the top 2000. Comparison with existing shape-based docking algorithms shows that our method has a better performance than the others in unbound docking while remaining competitive for bound docking cases. Conclusion We show for the first time that the 3D Zernike descriptors are adept in capturing shape complementarity at the protein-protein interface and useful for

  11. ClusPro: a fully automated algorithm for protein–protein docking

    OpenAIRE

    Comeau, Stephen R.; Gatchell, David W.; Vajda, Sandor; Camacho, Carlos J.

    2004-01-01

    ClusPro (http://nrc.bu.edu/cluster) represents the first fully automated, web-based program for the computational docking of protein structures. Users may upload the coordinate files of two protein structures through ClusPro's web interface, or enter the PDB codes of the respective structures, which ClusPro will then download from the PDB server (http://www.rcsb.org/pdb/). The docking algorithms evaluate billions of putative complexes, retaining a preset number with favorable surface compleme...

  12. Multiple ligand simultaneous docking: orchestrated dancing of ligands in binding sites of protein.

    Science.gov (United States)

    Li, Huameng; Li, Chenglong

    2010-07-30

    Present docking methodologies simulate only one single ligand at a time during docking process. In reality, the molecular recognition process always involves multiple molecular species. Typical protein-ligand interactions are, for example, substrate and cofactor in catalytic cycle; metal ion coordination together with ligand(s); and ligand binding with water molecules. To simulate the real molecular binding processes, we propose a novel multiple ligand simultaneous docking (MLSD) strategy, which can deal with all the above processes, vastly improving docking sampling and binding free energy scoring. The work also compares two search strategies: Lamarckian genetic algorithm and particle swarm optimization, which have respective advantages depending on the specific systems. The methodology proves robust through systematic testing against several diverse model systems: E. coli purine nucleoside phosphorylase (PNP) complex with two substrates, SHP2NSH2 complex with two peptides and Bcl-xL complex with ABT-737 fragments. In all cases, the final correct docking poses and relative binding free energies were obtained. In PNP case, the simulations also capture the binding intermediates and reveal the binding dynamics during the recognition processes, which are consistent with the proposed enzymatic mechanism. In the other two cases, conventional single-ligand docking fails due to energetic and dynamic coupling among ligands, whereas MLSD results in the correct binding modes. These three cases also represent potential applications in the areas of exploring enzymatic mechanism, interpreting noisy X-ray crystallographic maps, and aiding fragment-based drug design, respectively.

  13. Prediction of substrates for glutathione transferases by covalent docking.

    Science.gov (United States)

    Dong, Guang Qiang; Calhoun, Sara; Fan, Hao; Kalyanaraman, Chakrapani; Branch, Megan C; Mashiyama, Susan T; London, Nir; Jacobson, Matthew P; Babbitt, Patricia C; Shoichet, Brian K; Armstrong, Richard N; Sali, Andrej

    2014-06-23

    Enzymes in the glutathione transferase (GST) superfamily catalyze the conjugation of glutathione (GSH) to electrophilic substrates. As a consequence they are involved in a number of key biological processes, including protection of cells against chemical damage, steroid and prostaglandin biosynthesis, tyrosine catabolism, and cell apoptosis. Although virtual screening has been used widely to discover substrates by docking potential noncovalent ligands into active site clefts of enzymes, docking has been rarely constrained by a covalent bond between the enzyme and ligand. In this study, we investigate the accuracy of docking poses and substrate discovery in the GST superfamily, by docking 6738 potential ligands from the KEGG and MetaCyc compound libraries into 14 representative GST enzymes with known structures and substrates using the PLOP program [ Jacobson Proteins 2004 , 55 , 351 ]. For X-ray structures as receptors, one of the top 3 ranked models is within 3 Å all-atom root mean square deviation (RMSD) of the native complex in 11 of the 14 cases; the enrichment LogAUC value is better than random in all cases, and better than 25 in 7 of 11 cases. For comparative models as receptors, near-native ligand-enzyme configurations are often sampled but difficult to rank highly. For models based on templates with the highest sequence identity, the enrichment LogAUC is better than 25 in 5 of 11 cases, not significantly different from the crystal structures. In conclusion, we show that covalent docking can be a useful tool for substrate discovery and point out specific challenges for future method improvement.

  14. Crusader Automated Docking System: Technology support for the Crusader Resupply Team. Interim report, Ammunition Logistics Program

    Energy Technology Data Exchange (ETDEWEB)

    Kring, C.T.; Varma, V.K.; Jatko, W.B.

    1995-11-01

    The US Army and Team Crusader (United Defense, Lockheed Martin Armament Systems, etc.) are developing the next generation howitzer, the Crusader. The development program includes an advanced, self-propelled liquid propellant howitzer and a companion resupply vehicle. The resupply vehicle is intended to rendezvous with the howitzer near the battlefront and replenish ammunition, fuel, and other material. The Army has recommended that Crusader incorporate new and innovative technologies to improve performance and safety. One conceptual design proposes a robotic resupply boom on the resupply vehicle to upload supplies to the howitzer. The resupply boom would normally be retracted inside the resupply vehicle during transit. When the two vehicles are within range of the resupply boom, the boom would be extended to a receiving port on the howitzer. In order to reduce exposure to small arms fire or nuclear, biological, and chemical hazards, the crew would remain inside the resupply vehicle during the resupply operation. The process of extending the boom and linking with the receiving port is called docking. A boom operator would be designated to maneuver the boom into contact with the receiving port using a mechanical joystick. The docking operation depends greatly upon the skill of the boom operator to manipulate the boom into docking position. Computer simulations at the National Aeronautics and Space Administration have shown that computer-assisted or autonomous docking can improve the ability of the operator to dock safely and quickly. This document describes the present status of the Crusader Autonomous Docking System (CADS) implemented at Oak Ridge National laboratory (ORNL). The purpose of the CADS project is to determine the feasibility and performance limitations of vision systems to satisfy the autonomous docking requirements for Crusader and conduct a demonstration under controlled conditions.

  15. MAGIC: Marine ARM GPCI Investigation of Clouds

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, ER; Wiscombe, WJ; Albrecht, BA; Bland, GL; Flagg, CN; Klein, SA; Kollias, P; Mace, G; Reynolds, RM; Schwartz, SE; Siebesma, AP; Teixeira, J; Wood, R; Zhang, M

    2012-10-03

    The second Atmospheric Radiation Measurement (ARM) Mobile Facility (AMF2) will be deployed aboard the Horizon Lines cargo container ship merchant vessel (M/V) Spirit for MAGIC, the Marine ARM GPCI1 Investigation of Clouds. The Spirit will traverse the route between Los Angeles, California, and Honolulu, Hawaii, from October 2012 through September 2013 (except for a few months in the middle of this time period when the ship will be in dry dock). During this field campaign, AMF2 will observe and characterize the properties of clouds and precipitation, aerosols, and atmospheric radiation; standard meteorological and oceanographic variables; and atmospheric structure. There will also be two intensive observational periods (IOPs), one in January 2013 and one in July 2013, during which more detailed measurements of the atmospheric structure will be made.

  16. No dry dock: safely strategy for avoiding unplanned dry dock and reducing safety, health and environment risks

    Energy Technology Data Exchange (ETDEWEB)

    Constantinis, Danny A.; Brett, David E. [EM and I Alliance, Cheshire (United Kingdom)

    2012-07-01

    There are currently over 150 operational FPUs with an expected increase of a further 100 units in the next 5 years. This results from several factors: increasing demand for hydrocarbons; new reserves in deep water; pipeline infrastructure is not required and FPU design fits many field requirements. FPUs are increasingly chosen for large, deep water, longer life developments. Units are bigger and more complex. Regulators and oil majors are imposing more stringent integrity requirements to protect against safety, environmental and operational risks related to loss of containment and loss of hull structure integrity which could lead to HSE risks, increased costs and production losses which would become particularly onerous should the unit have to dry dock. There are a number of other important components the context of asset integrity, e.g. mooring and sub sea systems, but these are outside the scope of this paper. The 'No Dry dock....Safely' approach is based on the principle of Criticality Based Integrity which identifies components whose integrity is critical to avoiding incidents and the risk of dry docking. Once critical components are identified the challenge is to establish integrity status and maintain fitness-for-service. Various JIPs e.g. the Hull Inspection Techniques and Strategies are looking at best practice inspection methodologies. The industry is progressing ways of maintaining and repairing critical items without going to dry dock. The challenges include coating maintenance, structural and pressure system repairs. Advances in cathodic protection and coating maintenance strategies are proving successful as are techniques for carrying out major structural repairs. The 'No Dry dock...Safely' methodology is a proven solution and case histories have been included. Technological advances will further improve integrity in the industry. There is no reason why FPUs cannot be kept on station and in production for 25 years or more whilst

  17. Flexible Ligand Docking Using Differential Evolution

    DEFF Research Database (Denmark)

    Thomsen, René

    2003-01-01

    Molecular docking of biomolecules is becoming an increasingly important part in the process of developing new drugs, as well as searching compound databases for promising drug candidates. The docking of ligands to proteins can be formulated as an optimization problem where the task is to find...

  18. Why are most EU pigs tail docked?

    DEFF Research Database (Denmark)

    D'eath, R.B.; Niemi, J.K.; Vosough Ahmadi, B.

    2016-01-01

    To limit tail biting incidence, most pig producers in Europe tail dock their piglets. This is despite EU Council Directive 2008/120/EC banning routine tail docking and allowing it only as a last resort. The paper aims to understand what it takes to fulfil the intentions of the Directive by examin...

  19. A Review on Quantitative Approaches for Dock Door Assignment in Cross-Docking

    Directory of Open Access Journals (Sweden)

    Adibah Shuib

    2012-01-01

    Full Text Available Cross docking is a relatively new technique in supply chain operations. It offers limited storage time to maximize the efficiency of goods transshipment. Efficient operation of a cross docking system requires an appropriate coordination of inbound and outbound flows, accurate planning and dynamic scheduling.  The planning strategies at cross docking terminals, which are receiving growing attention today, are the truck-to-door assignment and destination to door assignment problems. This paper provides a comprehensive literature review of quantitative approaches in dock door assignment problems of cross docking planning. The contributions of this paper are to identify the gap of knowledge in operational levels mainly in dock door assignment and to point out the future research direction in cross docking.

  20. Dock180 expression in epithelial ovarian tumors

    Institute of Scientific and Technical Information of China (English)

    Hui Wang; Huhua Ling; Zhenwei Yao

    2012-01-01

    Objective: The aim of our study was to investigate the expression of guanine nucleotide exchange factor Dock180 in ovarian tumor, and its significance in the initiation and progression of ovarian cancer.Methods: Immunohistochemical staining with SP method was conducted to identify the expression of Dock180 protein in epithelial ovarian tumor in 68 cases.Results: Dock180 present with higher expression in ovarian cancer, as compared with than that in low malignant tumor and benign ovarian tumor (P < 0.01).In ovarian cancer, Dock180 expression was increased with the increased FIGO stage and grade.Conclusion: Dock180 overexpression may play an important role in the development and progression of ovarian cancer and it could be used as a new measurement of malignant biological behavior of ovarian cancer.

  1. Vehicle Routing Problem for Fashion Supply Chains with Cross-Docking

    Directory of Open Access Journals (Sweden)

    Zhi-Hua Hu

    2013-01-01

    Full Text Available Cross-docking, as a strategy to reduce lead time and enhance the efficiency of the fashion supply chain, has attracted substantial attention from both the academy and the industry. Cross-docking is a critical part of many fashion and textiles supply chains in practice because it can help to achieve many supply chain strategies such as postponement. We consider a model where there are multiple suppliers and customers in a single cross-docking center. With such a model setting, the issue concerning the coordinated routing between the inbound and outbound routes is much more complex than many traditional vehicle routing problems (VRPs. We formulate the optimal route selection problems from the suppliers to the cross-docking center and from the cross-docking center to the customers as the respective VRPs. Based on the relationships between the suppliers and the customers, we integrate the two VRP models to optimize the overall traveling time, distance, and waiting time at the cross-docking center. In addition, we propose a novel mixed 0/1 integer linear programming model by which the complexity of the problem can be reduced significantly. As demonstrated by the simulation analysis, our proposed model can be solved very efficiently by a commonly used optimization software package.

  2. Computational methods for molecular docking

    Energy Technology Data Exchange (ETDEWEB)

    Klebe, G. [BASF AG, Ludwigshafen (Germany); Lengauer, T.

    1995-12-31

    This tutorial was one of eight tutorials selected to be presented at the Third International Conference on Intelligent Systems for Molecular Biology which was held in the United Kingdom from July 16 to 19, 1995. Recently, it has been demonstrated that the knowledge of the three-dimensional structure of the protein can be used to derive new protein ligands with improved binding properties. This tutorial focuses on the following questions: What is its binding affinity toward a particular receptor? What are putative conformations of a ligand at the binding site? What are the similarities of different ligands in terms of their recognition capabilities? Where and in which orientation will a ligand bind to the active site? How is a new putative protein ligand selected? An overview is presented of the algorithms which are presently used to handle and predict protein-ligand interactions and to dock small molecule ligands into proteins.

  3. Laser docking sensor engineering model

    Science.gov (United States)

    Dekome, Kent; Barr, Joseph M.

    NASA JSC has been involved in the development of Laser sensors for the past ten years in order to support future rendezvous and docking missions, both manned and unmanned. Although many candidate technologies have been breadboarded and evaluated, no sensor hardware designed specifically for rendezvous and docking applications has been demonstrated on-orbit. It has become apparent that representative sensors need to be flown and demonstrated as soon as possible, with minimal cost, to provide the capability of the technology in meeting NASA's future AR&C applications. Technology and commercial component reliability have progressed to where it is now feasible to fly hardware as a detailed test objective minimizing the overall cost and development time. This presentation will discuss the ongoing effort to convert an existing in-house developed breadboard to an engineering model configuration suitable for flight. The modifications include improving the ranger resolution and stability with an in-house design, replacing the rack mounted galvanometric scanner drivers with STD-bus cards, replacing the system controlling personal computer with a microcontroller, and repackaging the subsystems as appropriate. The sensor will use the performance parameters defined in previous JSC requirements working groups as design goals and be built to withstand the space environment where fiscally feasible. Testing of the in-house ranger design is expected to be completed in October. The results will be included in the presentation. Preliminary testing of the ranging circuitry indicates a range resolution of 4mm is possible. The sensor will be mounted in the payload bay on a shelf bracket and have command, control, and display capabilities using the payload general support computer via an RS422 data line.

  4. Variation in the human Achilles tendon moment arm during walking.

    Science.gov (United States)

    Rasske, Kristen; Thelen, Darryl G; Franz, Jason R

    2017-02-01

    The Achilles tendon (AT) moment arm is an important determinant of ankle moment and power generation during locomotion. Load and depth-dependent variations in the AT moment arm are generally not considered, but may be relevant given the complex triceps surae architecture. We coupled motion analysis and ultrasound imaging to characterize AT moment arms during walking in 10 subjects. Muscle loading during push-off amplified the AT moment arm by 10% relative to heel strike. AT moment arms also varied by 14% over the tendon thickness. In walking, AT moment arms are not strictly dependent on kinematics, but exhibit important load and spatial dependencies.

  5. Dynamic/control interactions between flexible orbiting space-robot during grasping, docking and post-docking manoeuvres

    Science.gov (United States)

    Gasbarri, Paolo; Pisculli, Andrea

    2015-05-01

    Robotic systems are expected to play an increasingly important role in future space activities, such as repairing, upgrading, refuelling, and re-orbiting spacecraft. These technologies could potentially extend the life of satellites, enhance the capability of space systems, reduce the operation costs, and clean up the increasing space debris. Recent proposals for missions involving the use of space manipulators and/or automated transfer vehicles are presented as a solution for a lot of problems, which now affect the procedures and the performance of the in-orbit space systems. Other projects involving space manipulators have been developed by DARPA aiming to demonstrate several satellite servicing operations and technologies including rendez-vous, proximity operations and station-keeping, capture, docking, fluid transfer (specifically, "hydrazine"), and Orbit Replaceable Unit (ORU) transfer. Of course the dynamic coupling between the manipulator and its base mounting flexible solar arrays is very difficult to model. Furthermore, the motion planning of space robots is usually much more complicated than the motion planning of fixed-base manipulators. In this paper first of all the authors present a mixed NE/EL formulation suitable for synthesizing optimal control strategies during the deploying manoeuvres of robotic arms mounted on flexible orbiting platform (i.e. the chaser). Then two new control strategies able to compensate the flexibility excitations of the chaser satellite solar panels during the capturing of a flexible target spacecraft with the use of two robotic arms are presented and applied to a grasping manoeuvre. The mission is here divided into three main phases: the approaching, the docking and the post-grasping phase. Several numerical examples will complete the work.

  6. The binding of cytochrome c to neuroglobin: A docking and surface plasmon resonance study

    DEFF Research Database (Denmark)

    Bønding, Signe Helbo; Henty, K.; Dingley, A.J.;

    2008-01-01

    It has recently been proposed that the role of neuroglobin in the protection of neurons from ischaemia induced cell death requires the formation of a transient complex with cytochrome c. No such complex has yet been isolated. Here, we present the results of soft docking calculations, which indica...

  7. Advanced Docking System With Magnetic Initial Capture

    Science.gov (United States)

    Lewis, James L.; Carroll, Monty B.; Morales, Ray; Le, Thang

    2004-01-01

    An advanced docking system is undergoing development to enable softer, safer docking than was possible when using prior docking systems. This system is intended for original use in docking of visiting spacecraft and berthing the Crew Return Vehicle at the International Space Station (ISS). The system could also be adapted to a variety of other uses in outer space and on Earth, including mating submersible vehicles, assembling structures, and robotic berthing/handling of payloads and cargo. Heretofore, two large spacecraft have been docked by causing the spacecraft to approach each other at a speed sufficient to activate capture latches - a procedure that results in large docking loads and is made more difficult because of the speed. The basic design and mode of operation of the present advanced docking system would eliminate the need to rely on speed of approach to activate capture latches, thereby making it possible to reduce approach speed and thus docking loads substantially. The system would comprise an active subsystem on one spacecraft and a passive subsystem on another spacecraft with which the active subsystem will be docked. The passive subsystem would include an extensible ring containing magnetic striker plates and guide petals. The active subsystem would include mating guide petals and electromagnets containing limit switches and would be arranged to mate with the magnetic striker plates and guide petals of the passive assembly. The electromagnets would be carried on (but not rigidly attached to) a structural ring that would be instrumented with load sensors. The outputs of the sensors would be sent, along with position information, as feedback to an electronic control subsystem. The system would also include electromechanical actuators that would extend or retract the ring upon command by the control subsystem.

  8. Improved orthopedic arm joint

    Science.gov (United States)

    Dane, D. H.

    1971-01-01

    Joint permits smooth and easy movement of disabled arm and is smaller, lighter and less expensive than previous models. Device is interchangeable and may be used on either arm at the shoulder or at the elbow.

  9. Recovery of post stroke proximal arm function, driven by complex neuroplastic bilateral brain activation patterns and predicted by baseline motor dysfunction severity

    Directory of Open Access Journals (Sweden)

    Svetlana ePundik

    2015-07-01

    Full Text Available Objectives: Neuroplastic changes that drive recovery of shoulder/elbow function after stoke have been poorly understood. The purpose of this study was to determine the relationship between neuroplastic brain changes related to shoulder/elbow movement control in response to treatment and recovery of arm motor function in chronic stroke survivors. Methods: Twenty-three chronic stroke survivors were treated with 12 weeks of arm rehabilitation. Outcome measures included functional Magnetic Resonance Imaging (fMRI for the shoulder/elbow components of reach and a skilled motor function test (Arm Motor Abilities Test (AMAT, collected before and after treatment.Results: We observed two patterns of neuroplastic changes that were associated with gains in motor function: decreased or increased task-related brain activation. Those with significantly better motor function at baseline exhibited a decrease in brain activation in response to treatment, evident in the ipsilesional primary motor and contralesional supplementary motor regions; in contrast, those with greater baseline motor impairment, exhibited increased brain activation in response to treatment. There was an linear relationship between greater functional gain (AMAT and increased activation in bilateral primary motor, contralesional primary and secondary sensory regions, and contralesional lateral premotor area, after adjusting for baseline AMAT, age, and time since stroke. Conclusions: Recovery of functional reach involves recruitment of several contralesional and bilateral primary motor regions. In response to intensive therapy, the direction of functional brain change (i.e. increase or decrease in task-related brain recruitment for shoulder/elbow reach components depends on baseline level of motor function and may represent either different phases or different strategies of neuroplasticity that drive functional recovery.

  10. Development of a Robotics-based Satellites Docking Simulator

    NARCIS (Netherlands)

    Zebenay, M.

    2014-01-01

    The European Proximity Operation Simulator (EPOS) is a hardware-in-the-loop (HIL) system aiming, among other objectives, at emulating on-orbit docking of spacecraft for verification and validation of the docking phase. This HIL docking simulator set-up essentially consists of docking interfaces, sim

  11. Ultrafast de novo docking combining pharmacophores and combinatorics.

    Science.gov (United States)

    Gastreich, Marcus; Lilienthal, Markus; Briem, Hans; Claussen, Holger

    2006-12-01

    We report on a successful de novo design approach which relies on the combination of multi-million compound combinatorial docking under receptor-based pharmacophore constraints. Inspired by a rationale by A.R. Leach et al., we document on the unification of two steps into one for ligand assembly. In the original work, fragments known to bind in protein active sites were connected forming novel ligand compounds by means of generic skeleton linkers and following a combinatorial approach. In our approach, the knowledge of fragments binding to the protein has been expressed in terms of a receptor-based pharmacophore definition. The combinatorial linking step is performed in situ during docking, starting from combinatorial libraries. Three sample scenarios growing in size and complexity (combinatorial libraries of 1 million, 1.3 million, and 22.4 million compounds) have been created to illustrate the method. Docking could be accomplished between minutes and several hours depending on the outset; the results were throughout promising. Technically, a module compatibility between FlexX(C) and FlexX-Pharm has been established. The background is explained, and the crucial points from an information scientist's perspective are highlighted.

  12. Molecular Docking and Structure-Based Drug Design Strategies

    Directory of Open Access Journals (Sweden)

    Leonardo G. Ferreira

    2015-07-01

    Full Text Available Pharmaceutical research has successfully incorporated a wealth of molecular modeling methods, within a variety of drug discovery programs, to study complex biological and chemical systems. The integration of computational and experimental strategies has been of great value in the identification and development of novel promising compounds. Broadly used in modern drug design, molecular docking methods explore the ligand conformations adopted within the binding sites of macromolecular targets. This approach also estimates the ligand-receptor binding free energy by evaluating critical phenomena involved in the intermolecular recognition process. Today, as a variety of docking algorithms are available, an understanding of the advantages and limitations of each method is of fundamental importance in the development of effective strategies and the generation of relevant results. The purpose of this review is to examine current molecular docking strategies used in drug discovery and medicinal chemistry, exploring the advances in the field and the role played by the integration of structure- and ligand-based methods.

  13. Modelling substrate specificity and enantioselectivity for lipases and esterases by substrate-imprinted docking

    Directory of Open Access Journals (Sweden)

    Tyagi Sadhna

    2009-06-01

    Full Text Available Abstract Background Previously, ways to adapt docking programs that were developed for modelling inhibitor-receptor interaction have been explored. Two main issues were discussed. First, when trying to model catalysis a reaction intermediate of the substrate is expected to provide more valid information than the ground state of the substrate. Second, the incorporation of protein flexibility is essential for reliable predictions. Results Here we present a predictive and robust method to model substrate specificity and enantioselectivity of lipases and esterases that uses reaction intermediates and incorporates protein flexibility. Substrate-imprinted docking starts with covalent docking of reaction intermediates, followed by geometry optimisation of the resulting enzyme-substrate complex. After a second round of docking the same substrate into the geometry-optimised structures, productive poses are identified by geometric filter criteria and ranked by their docking scores. Substrate-imprinted docking was applied in order to model (i enantioselectivity of Candida antarctica lipase B and a W104A mutant, (ii enantioselectivity and substrate specificity of Candida rugosa lipase and Burkholderia cepacia lipase, and (iii substrate specificity of an acetyl- and a butyrylcholine esterase toward the substrates acetyl- and butyrylcholine. Conclusion The experimentally observed differences in selectivity and specificity of the enzymes were reproduced with an accuracy of 81%. The method was robust toward small differences in initial structures (different crystallisation conditions or a co-crystallised ligand, although large displacements of catalytic residues often resulted in substrate poses that did not pass the geometric filter criteria.

  14. Arm Lift (Brachioplasty)

    Science.gov (United States)

    ... sagging. An arm lift might also boost your body image. As you get older, the skin on your upper arms changes — sagging and becoming loose. Significant weight loss also can cause the undersides of your upper arms to droop. While exercise can strengthen and improve muscle tone in the ...

  15. Ranking multiple docking solutions based on the conservation of inter-residue contacts

    KAUST Repository

    Oliva, Romina M.

    2013-06-17

    Molecular docking is the method of choice for investigating the molecular basis of recognition in a large number of functional protein complexes. However, correctly scoring the obtained docking solutions (decoys) to rank native-like (NL) conformations in the top positions is still an open problem. Herein we present CONSRANK, a simple and effective tool to rank multiple docking solutions, which relies on the conservation of inter-residue contacts in the analyzed decoys ensemble. First it calculates a conservation rate for each inter-residue contact, then it ranks decoys according to their ability to match the more frequently observed contacts. We applied CONSRANK to 102 targets from three different benchmarks, RosettaDock, DOCKGROUND, and Critical Assessment of PRedicted Interactions (CAPRI). The method performs consistently well, both in terms of NL solutions ranked in the top positions and of values of the area under the receiver operating characteristic curve. Its ideal application is to solutions coming from different docking programs and procedures, as in the case of CAPRI targets. For all the analyzed CAPRI targets where a comparison is feasible, CONSRANK outperforms the CAPRI scorers. The fraction of NL solutions in the top ten positions in the RosettaDock, DOCKGROUND, and CAPRI benchmarks is enriched on average by a factor of 3.0, 1.9, and 9.9, respectively. Interestingly, CONSRANK is also able to specifically single out the high/medium quality (HMQ) solutions from the docking decoys ensemble: it ranks 46.2 and 70.8% of the total HMQ solutions available for the RosettaDock and CAPRI targets, respectively, within the top 20 positions. © 2013 Wiley Periodicals, Inc.

  16. Effects of tail docking and docking length on neuroanatomical changes in healed tail tips of pigs

    DEFF Research Database (Denmark)

    Herskin, M S; Thodberg, K; Jensen, Henrik Elvang

    2015-01-01

    In pig production, piglets are tail docked at birth in order to prevent tail biting later in life. In order to examine the effects of tail docking and docking length on the formation of neuromas, we used 65 pigs and the following four treatments: intact tails (n=18); leaving 75% (n=17); leaving 50......% (n=19); or leaving 25% (n=11) of the tail length on the pigs. The piglets were docked between day 2 and 4 after birth using a gas-heated apparatus, and were kept under conventional conditions until slaughter at 22 weeks of age, where tails were removed and examined macroscopically and histologically...

  17. Accounting for large amplitude protein deformation during in silico macromolecular docking.

    Science.gov (United States)

    Bastard, Karine; Saladin, Adrien; Prévost, Chantal

    2011-02-22

    Rapid progress of theoretical methods and computer calculation resources has turned in silico methods into a conceivable tool to predict the 3D structure of macromolecular assemblages, starting from the structure of their separate elements. Still, some classes of complexes represent a real challenge for macromolecular docking methods. In these complexes, protein parts like loops or domains undergo large amplitude deformations upon association, thus remodeling the surface accessible to the partner protein or DNA. We discuss the problems linked with managing such rearrangements in docking methods and we review strategies that are presently being explored, as well as their limitations and success.

  18. Accounting for Large Amplitude Protein Deformation during in Silico Macromolecular Docking

    Directory of Open Access Journals (Sweden)

    Chantal Prévost

    2011-02-01

    Full Text Available Rapid progress of theoretical methods and computer calculation resources has turned in silico methods into a conceivable tool to predict the 3D structure of macromolecular assemblages, starting from the structure of their separate elements. Still, some classes of complexes represent a real challenge for macromolecular docking methods. In these complexes, protein parts like loops or domains undergo large amplitude deformations upon association, thus remodeling the surface accessible to the partner protein or DNA.We discuss the problems linked with managing such rearrangements in docking methods and we review strategies that are presently being explored, as well as their limitations and success.

  19. Dockomatic - automated ligand creation and docking

    OpenAIRE

    Hampikian Greg; McDougal Owen M; Jacob Reed B; Bullock Casey W; Andersen Tim

    2010-01-01

    Abstract Background The application of computational modeling to rationally design drugs and characterize macro biomolecular receptors has proven increasingly useful due to the accessibility of computing clusters and clouds. AutoDock is a well-known and powerful software program used to model ligand to receptor binding interactions. In its current version, AutoDock requires significant amounts of user time to setup and run jobs, and collect results. This paper presents DockoMatic, a user frie...

  20. Triangulation methods for automated docking

    Science.gov (United States)

    Bales, John W.

    1996-01-01

    An automated docking system must have a reliable method for determining range and orientation of the passive (target) vehicle with respect to the active vehicle. This method must also provide accurate information on the rates of change of range to and orientation of the passive vehicle. The method must be accurate within required tolerances and capable of operating in real time. The method being developed at Marshall Space Flight Center employs a single TV camera, a laser illumination system and a target consisting, in its minimal configuration, of three retro-reflectors. Two of the retro-reflectors are mounted flush to the same surface, with the third retro-reflector mounted to a post fixed midway between the other two and jutting at a right angle from the surface. For redundancy, two additional retroreflectors are mounted on the surface on a line at right angles to the line containing the first two retro-reflectors, and equally spaced on either side of the post. The target vehicle will contain a large target for initial acquisition and several smaller targets for close range.

  1. Nonlinear scoring functions for similarity-based ligand docking and binding affinity prediction.

    Science.gov (United States)

    Brylinski, Michal

    2013-11-25

    A common strategy for virtual screening considers a systematic docking of a large library of organic compounds into the target sites in protein receptors with promising leads selected based on favorable intermolecular interactions. Despite a continuous progress in the modeling of protein-ligand interactions for pharmaceutical design, important challenges still remain, thus the development of novel techniques is required. In this communication, we describe eSimDock, a new approach to ligand docking and binding affinity prediction. eSimDock employs nonlinear machine learning-based scoring functions to improve the accuracy of ligand ranking and similarity-based binding pose prediction, and to increase the tolerance to structural imperfections in the target structures. In large-scale benchmarking using the Astex/CCDC data set, we show that 53.9% (67.9%) of the predicted ligand poses have RMSD of <2 Å (<3 Å). Moreover, using binding sites predicted by recently developed eFindSite, eSimDock models ligand binding poses with an RMSD of 4 Å for 50.0-39.7% of the complexes at the protein homology level limited to 80-40%. Simulations against non-native receptor structures, whose mean backbone rearrangements vary from 0.5 to 5.0 Å Cα-RMSD, show that the ratio of docking accuracy and the estimated upper bound is at a constant level of ∼0.65. Pearson correlation coefficient between experimental and predicted by eSimDock Ki values for a large data set of the crystal structures of protein-ligand complexes from BindingDB is 0.58, which decreases only to 0.46 when target structures distorted to 3.0 Å Cα-RMSD are used. Finally, two case studies demonstrate that eSimDock can be customized to specific applications as well. These encouraging results show that the performance of eSimDock is largely unaffected by the deformations of ligand binding regions, thus it represents a practical strategy for across-proteome virtual screening using protein models. eSimDock is freely

  2. Docking validation resources: protein family and ligand flexibility experiments.

    Science.gov (United States)

    Mukherjee, Sudipto; Balius, Trent E; Rizzo, Robert C

    2010-11-22

    A database consisting of 780 ligand-receptor complexes, termed SB2010, has been derived from the Protein Databank to evaluate the accuracy of docking protocols for regenerating bound ligand conformations. The goal is to provide easily accessible community resources for development of improved procedures to aid virtual screening for ligands with a wide range of flexibilities. Three core experiments using the program DOCK, which employ rigid (RGD), fixed anchor (FAD), and flexible (FLX) protocols, were used to gauge performance by several different metrics: (1) global results, (2) ligand flexibility, (3) protein family, and (4) cross-docking. Global spectrum plots of successes and failures vs rmsd reveal well-defined inflection regions, which suggest the commonly used 2 Å criteria is a reasonable choice for defining success. Across all 780 systems, success tracks with the relative difficulty of the calculations: RGD (82.3%) > FAD (78.1%) > FLX (63.8%). In general, failures due to scoring strongly outweigh those due to sampling. Subsets of SB2010 grouped by ligand flexibility (7-or-less, 8-to-15, and 15-plus rotatable bonds) reveal that success degrades linearly for FAD and FLX protocols, in contrast to RGD, which remains constant. Despite the challenges associated with FLX anchor orientation and on-the-fly flexible growth, success rates for the 7-or-less (74.5%) and, in particular, the 8-to-15 (55.2%) subset are encouraging. Poorer results for the very flexible 15-plus set (39.3%) indicate substantial room for improvement. Family-based success appears largely independent of ligand flexibility, suggesting a strong dependence on the binding site environment. For example, zinc-containing proteins are generally problematic, despite moderately flexible ligands. Finally, representative cross-docking examples, for carbonic anhydrase, thermolysin, and neuraminidase families, show the utility of family-based analysis for rapid identification of particularly good or bad

  3. Evaluation of multiple protein docking structures using correctly predicted pairwise subunits

    Directory of Open Access Journals (Sweden)

    Esquivel-Rodríguez Juan

    2012-03-01

    Full Text Available Abstract Background Many functionally important proteins in a cell form complexes with multiple chains. Therefore, computational prediction of multiple protein complexes is an important task in bioinformatics. In the development of multiple protein docking methods, it is important to establish a metric for evaluating prediction results in a reasonable and practical fashion. However, since there are only few works done in developing methods for multiple protein docking, there is no study that investigates how accurate structural models of multiple protein complexes should be to allow scientists to gain biological insights. Methods We generated a series of predicted models (decoys of various accuracies by our multiple protein docking pipeline, Multi-LZerD, for three multi-chain complexes with 3, 4, and 6 chains. We analyzed the decoys in terms of the number of correctly predicted pair conformations in the decoys. Results and conclusion We found that pairs of chains with the correct mutual orientation exist even in the decoys with a large overall root mean square deviation (RMSD to the native. Therefore, in addition to a global structure similarity measure, such as the global RMSD, the quality of models for multiple chain complexes can be better evaluated by using the local measurement, the number of chain pairs with correct mutual orientation. We termed the fraction of correctly predicted pairs (RMSD at the interface of less than 4.0Å as fpair and propose to use it for evaluation of the accuracy of multiple protein docking.

  4. PTools: an opensource molecular docking library

    Directory of Open Access Journals (Sweden)

    Poulain Pierre

    2009-05-01

    Full Text Available Abstract Background Macromolecular docking is a challenging field of bioinformatics. Developing new algorithms is a slow process generally involving routine tasks that should be found in a robust library and not programmed from scratch for every new software application. Results We present an object-oriented Python/C++ library to help the development of new docking methods. This library contains low-level routines like PDB-format manipulation functions as well as high-level tools for docking and analyzing results. We also illustrate the ease of use of this library with the detailed implementation of a 3-body docking procedure. Conclusion The PTools library can handle molecules at coarse-grained or atomic resolution and allows users to rapidly develop new software. The library is already in use for protein-protein and protein-DNA docking with the ATTRACT program and for simulation analysis. This library is freely available under the GNU GPL license, together with detailed documentation.

  5. Surfing the Protein-Protein Interaction Surface Using Docking Methods: Application to the Design of PPI Inhibitors

    Directory of Open Access Journals (Sweden)

    Rushikesh Sable

    2015-06-01

    Full Text Available Blocking protein-protein interactions (PPI using small molecules or peptides modulates biochemical pathways and has therapeutic significance. PPI inhibition for designing drug-like molecules is a new area that has been explored extensively during the last decade. Considering the number of available PPI inhibitor databases and the limited number of 3D structures available for proteins, docking and scoring methods play a major role in designing PPI inhibitors as well as stabilizers. Docking methods are used in the design of PPI inhibitors at several stages of finding a lead compound, including modeling the protein complex, screening for hot spots on the protein-protein interaction interface and screening small molecules or peptides that bind to the PPI interface. There are three major challenges to the use of docking on the relatively flat surfaces of PPI. In this review we will provide some examples of the use of docking in PPI inhibitor design as well as its limitations. The combination of experimental and docking methods with improved scoring function has thus far resulted in few success stories of PPI inhibitors for therapeutic purposes. Docking algorithms used for PPI are in the early stages, however, and as more data are available docking will become a highly promising area in the design of PPI inhibitors or stabilizers.

  6. Synthesis and characterization of Ni(II, Cu(II and Co(III complexes with polyamine-containing macrocycles bearing an aminoethyl pendant arm

    Directory of Open Access Journals (Sweden)

    K. S. SIDDIQI

    2004-09-01

    Full Text Available Reaction of [M(ppn2]X2 (where M = Cu(II, Ni(II, Co(II and ppn = 1,3-diaminopropane with formaldehyde and ethylenediamine in methanol results in the ready formation of a 16-membered macrocyclic complex. The complexes were characterized by elemental anlysis, IR, EPR, electronic spectral data, magnetic moments and conductance measurements. The Cu(II, Ni(II and Co(III complexes are coordinated axially with both pendant groups of the hexadentate macrocycle. These pendant donors are attached to the macrocycle by a carbon chain. The electrical conductivities of the Cu(II and Ni(II chelates indicated them to be 1:2 electrolytes whilst those of Co(III is a 1:3 electrolyte in DMSO. The EPR spectrum of the copper complex exhibited G at 3.66, which indicates a considerable exchange interaction in the complex. Spectroscopic evidence suggests that in all of the complexes the metal ion is in an octahedral environment.

  7. Advances in GPCR modeling evaluated by the GPCR Dock 2013 assessment

    DEFF Research Database (Denmark)

    Kufareva, Irina; Katritch, Vsevolod; Biggin, Phil

    2014-01-01

    Despite tremendous successes of GPCR crystallography, the receptors with available structures represent only a small fraction of human GPCRs. An important role of the modeling community is to maximize structural insights for the remaining receptors and complexes. The community-wide GPCR Dock asse...

  8. Molecular Docking of Enzyme Inhibitors: A Computational Tool for Structure-Based Drug Design

    Science.gov (United States)

    Rudnitskaya, Aleksandra; Torok, Bela; Torok, Marianna

    2010-01-01

    Molecular docking is a frequently used method in structure-based rational drug design. It is used for evaluating the complex formation of small ligands with large biomolecules, predicting the strength of the bonding forces and finding the best geometrical arrangements. The major goal of this advanced undergraduate biochemistry laboratory exercise…

  9. Late First-Row Transition-Metal Complexes Containing a 2-Pyridylmethyl Pendant-Armed 15-Membered Macrocyclic Ligand. Field-Induced Slow Magnetic Relaxation in a Seven-Coordinate Cobalt(II) Compound.

    Science.gov (United States)

    Antal, Peter; Drahoš, Bohuslav; Herchel, Radovan; Trávníček, Zdeněk

    2016-06-20

    The 2-pyridylmethyl N-pendant-armed heptadentate macrocyclic ligand {3,12-bis(2-methylpyridine)-3,12,18-triaza-6,9-dioxabicyclo[12.3.1]octadeca-1,14,16-triene = L} and [M(L)](ClO4)2 complexes, where M = Mn(II) (1), Fe(II) (2), Co(II) (3), Ni(II) (4), and Cu(II) (5), were prepared and thoroughly characterized, including elucidation of X-ray structures of all the compounds studied. The complexes 1-5 crystallize in non-centrosymmetric Sohncke space groups as racemic compounds. The coordination numbers of 7, 6 + 1, and 5 were found in complexes 1-3, 4, and 5, respectively, with a distorted pentagonal bipyramidal (1-4) or square pyramidal (5) geometry. On the basis of the magnetic susceptibility experiments, a large axial zero-field splitting (ZFS) was found for 2, 3, and 4 (D(Fe) = -7.4(2) cm(-1), D(Co) = 34(1) cm(-1), and D(Ni) = -12.8(1) cm(-1), respectively) together with a rhombic ZFS (E/D = 0.136(3)) for 4. Despite the easy plane anisotropy (D > 0, E/D = 0) in 3, the slow relaxation of the magnetization below 8 K was observed and analyzed either with Orbach relaxation mechanism (the relaxation time τ0 = 9.90 × 10(-10) s and spin reversal barrier Ueff = 24.3 K (16.9 cm(-1))) or with Raman relaxation mechanism (C = 2.12 × 10(-5) and n = 2.84). Therefore, compound 3 enlarges the small family of field-induced single-molecule magnets with pentagonal-bipyramidal chromophore. The cyclic voltammetry in acetonitrile revealed reversible redox processes in 1-3 and 5, except for the Ni(II) complex 4, where a quasi-reversible process was dominantly observed. Presence of the two 2-pyridylmethyl pendant arms in L with a stronger σ-donor/π-acceptor ability had a great impact on the properties of all the complexes (1-5), concretely: (i) strong pyridine-metal bonds provided slight axial compression of the coordination sphere, (ii) substantial changes in magnetic anisotropy, and (iii) stabilization of lower oxidation states.

  10. Targeting RING domains of Mdm2-MdmX E3 complex activates apoptotic arm of the p53 pathway in leukemia/lymphoma cells.

    Science.gov (United States)

    Wu, W; Xu, C; Ling, X; Fan, C; Buckley, B P; Chernov, M V; Ellis, L; Li, F; Muñoz, I G; Wang, X

    2015-12-31

    Reactivation of tumor-suppressor p53 for targeted cancer therapy is an attractive strategy for cancers bearing wild-type (WT) p53. Targeting the Mdm2-p53 interface or MdmX ((MDM4), mouse double minute 4)-p53 interface or both has been a focus in the field. However, targeting the E3 ligase activity of Mdm2-MdmX really interesting new gene (RING)-RING interaction as a novel anticancer strategy has never been explored. In this report, we describe the identification and characterization of small molecule inhibitors targeting Mdm2-MdmX RING-RING interaction as a new class of E3 ligase inhibitors. With a fluorescence resonance energy transfer-based E3 activity assay in high-throughput screening of a chemical library, we identified inhibitors (designated as MMRis (Mdm2-MdmX RING domain inhibitors)) that specifically inhibit Mdm2-MdmX E3 ligase activity toward Mdm2 and p53 substrates. MMRi6 and its analog MMRi64 are capable of disrupting Mdm2-MdmX interactions in vitro and activating p53 in cells. In leukemia cells, MMRi64 potently induces downregulation of Mdm2 and MdmX. In contrast to Nutlin3a, MMRi64 only induces the expression of pro-apoptotic gene PUMA (p53 upregulated modulator of apoptosis) with minimal induction of growth-arresting gene p21. Consequently, MMRi64 selectively induces the apoptotic arm of the p53 pathway in leukemia/lymphoma cells. Owing to the distinct mechanisms of action of MMRi64 and Nutlin3a, their combination synergistically induces p53 and apoptosis. Taken together, this study reveals that Mdm2-MdmX has a critical role in apoptotic response of the p53 pathway and MMRi64 may serve as a new pharmacological tool for p53 studies and a platform for cancer drug development.

  11. CALET docked on the ISS

    CERN Document Server

    Antonella Del Rosso

    2015-01-01

    On 19 August, with a spectacular launch on board the Japanese H2-B rocket operated by the Japan Aerospace Exploration Agency (JAXA), the CALorimetric Electron Telescope (CALET) left the Tanegashima Space Center to reach the International Space Station five days later.   After berthing with the ISS, CALET was extracted by a robotic arm from the Japanese HTV-5 transfer vehicle and installed on the Japanese Exposure Facility (right) where it will start its first data-taking. (Image: NASA/JAXA.)   CALET is a space mission led by JAXA with the participation of the Italian Space Agency (ASI) and NASA. It is a CERN-recognised experiment and the second high-energy astroparticle experiment to be installed on the International Space Station (ISS) after AMS-02, which has been taking data since 2011. Designed to be a space observatory for long-term observations of cosmic radiation aboard the external platform JEM-EF of the Japanese module (KIBO) on the ISS, CALET aims to identify elect...

  12. Assessing the applicability of template-based protein docking in the twilight zone.

    Science.gov (United States)

    Negroni, Jacopo; Mosca, Roberto; Aloy, Patrick

    2014-09-02

    The structural modeling of protein interactions in the absence of close homologous templates is a challenging task. Recently, template-based docking methods have emerged to exploit local structural similarities to help ab-initio protocols provide reliable 3D models for protein interactions. In this work, we critically assess the performance of template-based docking in the twilight zone. Our results show that, while it is possible to find templates for nearly all known interactions, the quality of the obtained models is rather limited. We can increase the precision of the models at expenses of coverage, but it drastically reduces the potential applicability of the method, as illustrated by the whole-interactome modeling of nine organisms. Template-based docking is likely to play an important role in the structural characterization of the interaction space, but we still need to improve the repertoire of structural templates onto which we can reliably model protein complexes.

  13. Using RosettaLigand for small molecule docking into comparative models.

    Directory of Open Access Journals (Sweden)

    Kristian W Kaufmann

    Full Text Available Computational small molecule docking into comparative models of proteins is widely used to query protein function and in the development of small molecule therapeutics. We benchmark RosettaLigand docking into comparative models for nine proteins built during CASP8 that contain ligands. We supplement the study with 21 additional protein/ligand complexes to cover a wider space of chemotypes. During a full docking run in 21 of the 30 cases, RosettaLigand successfully found a native-like binding mode among the top ten scoring binding modes. From the benchmark cases we find that careful template selection based on ligand occupancy provides the best chance of success while overall sequence identity between template and target do not appear to improve results. We also find that binding energy normalized by atom number is often less than -0.4 in native-like binding modes.

  14. ARM Mentor Selection Process

    Energy Technology Data Exchange (ETDEWEB)

    Sisterson, D. L. [Argonne National Lab. (ANL), Argonne, IL (United States)

    2015-10-01

    The Atmospheric Radiation Measurement (ARM) Program was created in 1989 with funding from the U.S. Department of Energy (DOE) to develop several highly instrumented ground stations to study cloud formation processes and their influence on radiative transfer. In 2003, the ARM Program became a national scientific user facility, known as the ARM Climate Research Facility. This scientific infrastructure provides for fixed sites, mobile facilities, an aerial facility, and a data archive available for use by scientists worldwide through the ARM Climate Research Facility—a scientific user facility. The ARM Climate Research Facility currently operates more than 300 instrument systems that provide ground-based observations of the atmospheric column. To keep ARM at the forefront of climate observations, the ARM infrastructure depends heavily on instrument scientists and engineers, also known as lead mentors. Lead mentors must have an excellent understanding of in situ and remote-sensing instrumentation theory and operation and have comprehensive knowledge of critical scale-dependent atmospheric processes. They must also possess the technical and analytical skills to develop new data retrievals that provide innovative approaches for creating research-quality data sets. The ARM Climate Research Facility is seeking the best overall qualified candidate who can fulfill lead mentor requirements in a timely manner.

  15. SwarmDock and the Use of Normal Modes in Protein-Protein Docking

    Directory of Open Access Journals (Sweden)

    Paul A. Bates

    2010-09-01

    Full Text Available Here is presented an investigation of the use of normal modes in protein-protein docking, both in theory and in practice. Upper limits of the ability of normal modes to capture the unbound to bound conformational change are calculated on a large test set, with particular focus on the binding interface, the subset of residues from which the binding energy is calculated. Further, the SwarmDock algorithm is presented, to demonstrate that the modelling of conformational change as a linear combination of normal modes is an effective method of modelling flexibility in protein-protein docking.

  16. Investigation on Al(III) and Zn(II) complexes containing a calix[4]arene bearing two 8-oxyquinoline pendant arms used as emitting materials for OLEDs

    Energy Technology Data Exchange (ETDEWEB)

    Bagatin, Izilda A. [Instituto de Quimica, Universidade de Sao Paulo, Cx. P.: 26077, CEP 05513-970, Sao Paulo, SP (Brazil)], E-mail: izildabagatin@yahoo.com.br; Legnani, Cristiano [Divisao de Metrologia em Materiais, Instituto Nacional de Metrologia, Normalizacao e Qualidade Industrial, CEP 25250-020, Duque de Caxias, RJ (Brazil); Cremona, Marco [Divisao de Metrologia em Materiais, Instituto Nacional de Metrologia, Normalizacao e Qualidade Industrial, CEP 25250-020, Duque de Caxias, RJ (Brazil); Pontificia Universidade Catolica do Rio de Janeiro, Depto de Fisica, C.P.38071, Rio de Janeiro (Brazil)

    2009-01-01

    A comparison between [Al{center_dot}1]{sup 3+} and [Zn{center_dot}1]{sup 2+} complexes (1 = 5,11,17,23-tetra-tert-butyl-25,27-bis[(quinoline-8-oxy)propyloxy]-26, 28-dihydroxy-calix[4]arene) has been made using electrochemical techniques and the experimental results obtained in the fabrication of organic light emitting devices (OLEDs). The electrochemically determined values of the ionization potential I{sub p} and electron affinity E{sub a} parameters for the [Al{center_dot}1]{sup 3+} (I{sub p} = 5.82eV, E{sub a} = 2.80eV) and [Zn{center_dot}1]{sup 2+} (I{sub p} = 5.67eV, E{sub a} = 2.32eV) evidenced that the [Al{center_dot}1]{sup 3+} complex is a better electron transporting layer with respect to the Zn complex one. The fabricated OLEDs based on these supramolecular complexes show a superior quality with the [Al{center_dot}1]{sup 3+} systems expected from the energy level diagrams.

  17. Solving Molecular Docking Problems with Multi-Objective Metaheuristics

    Directory of Open Access Journals (Sweden)

    María Jesús García-Godoy

    2015-06-01

    Full Text Available Molecular docking is a hard optimization problem that has been tackled in the past with metaheuristics, demonstrating new and challenging results when looking for one objective: the minimum binding energy. However, only a few papers can be found in the literature that deal with this problem by means of a multi-objective approach, and no experimental comparisons have been made in order to clarify which of them has the best overall performance. In this paper, we use and compare, for the first time, a set of representative multi-objective optimization algorithms applied to solve complex molecular docking problems. The approach followed is focused on optimizing the intermolecular and intramolecular energies as two main objectives to minimize. Specifically, these algorithms are: two variants of the non-dominated sorting genetic algorithm II (NSGA-II, speed modulation multi-objective particle swarm optimization (SMPSO, third evolution step of generalized differential evolution (GDE3, multi-objective evolutionary algorithm based on decomposition (MOEA/D and S-metric evolutionary multi-objective optimization (SMS-EMOA. We assess the performance of the algorithms by applying quality indicators intended to measure convergence and the diversity of the generated Pareto front approximations. We carry out a comparison with another reference mono-objective algorithm in the problem domain (Lamarckian genetic algorithm (LGA provided by the AutoDock tool. Furthermore, the ligand binding site and molecular interactions of computed solutions are analyzed, showing promising results for the multi-objective approaches. In addition, a case study of application for aeroplysinin-1 is performed, showing the effectiveness of our multi-objective approach in drug discovery.

  18. Solving molecular docking problems with multi-objective metaheuristics.

    Science.gov (United States)

    García-Godoy, María Jesús; López-Camacho, Esteban; García-Nieto, José; Aldana-Montes, Antonio J Nebroand José F

    2015-06-02

    Molecular docking is a hard optimization problem that has been tackled in the past with metaheuristics, demonstrating new and challenging results when looking for one objective: the minimum binding energy. However, only a few papers can be found in the literature that deal with this problem by means of a multi-objective approach, and no experimental comparisons have been made in order to clarify which of them has the best overall performance. In this paper, we use and compare, for the first time, a set of representative multi-objective optimization algorithms applied to solve complex molecular docking problems. The approach followed is focused on optimizing the intermolecular and intramolecular energies as two main objectives to minimize. Specifically, these algorithms are: two variants of the non-dominated sorting genetic algorithm II (NSGA-II), speed modulation multi-objective particle swarm optimization (SMPSO), third evolution step of generalized differential evolution (GDE3), multi-objective evolutionary algorithm based on decomposition (MOEA/D) and S-metric evolutionary multi-objective optimization (SMS-EMOA). We assess the performance of the algorithms by applying quality indicators intended to measure convergence and the diversity of the generated Pareto front approximations. We carry out a comparison with another reference mono-objective algorithm in the problem domain (Lamarckian genetic algorithm (LGA) provided by the AutoDock tool). Furthermore, the ligand binding site and molecular interactions of computed solutions are analyzed, showing promising results for the multi-objective approaches. In addition, a case study of application for aeroplysinin-1 is performed, showing the effectiveness of our multi-objective approach in drug discovery.

  19. Protein-peptide molecular docking with large-scale conformational changes: the p53-MDM2 interaction

    Science.gov (United States)

    Ciemny, Maciej Pawel; Debinski, Aleksander; Paczkowska, Marta; Kolinski, Andrzej; Kurcinski, Mateusz; Kmiecik, Sebastian

    2016-12-01

    Protein-peptide interactions are often associated with large-scale conformational changes that are difficult to study either by classical molecular modeling or by experiment. Recently, we have developed the CABS-dock method for flexible protein-peptide docking that enables large-scale rearrangements of the protein chain. In this study, we use CABS-dock to investigate the binding of the p53-MDM2 complex, an element of the cell cycle regulation system crucial for anti-cancer drug design. Experimental data suggest that p53-MDM2 binding is affected by significant rearrangements of a lid region - the N-terminal highly flexible MDM2 fragment; however, the details are not clear. The large size of the highly flexible MDM2 fragments makes p53-MDM2 intractable for exhaustive binding dynamics studies using atomistic models. We performed extensive dynamics simulations using the CABS-dock method, including large-scale structural rearrangements of MDM2 flexible regions. Without a priori knowledge of the p53 peptide structure or its binding site, we obtained near-native models of the p53-MDM2 complex. The simulation results match well the experimental data and provide new insights into the possible role of the lid fragment in p53 binding. The presented case study demonstrates that CABS-dock methodology opens up new opportunities for protein-peptide docking with large-scale changes of the protein receptor structure.

  20. Docking to flexible nicotinic acetylcholine receptors

    DEFF Research Database (Denmark)

    Sander, Tommy; Bruun, Anne T; Balle, Thomas

    2010-01-01

    Computational docking to nicotinic acetylcholine receptors (nAChRs) and other members of the Cys-loop receptor family is complicated by the flexibility of the so-called C-loop. As observed in the large number of published crystal structures of the acetylcholine binding protein (AChBP), a structural...

  1. Nonspecific Arm Pain

    Directory of Open Access Journals (Sweden)

    Ali Moradi

    2013-12-01

    Full Text Available Nonspecific activity-related arm pain is characterized by an absence of objective physical findings and symptoms that do not correspond with objective pathophysiology. Arm pain without strict diagnosis is often related to activity, work-related activity in particular, and is often seen in patients with physically demanding work. Psychological factors such as catastrophic thinking, symptoms of depression, and heightened illness concern determine a substantial percentage of the disability associated with puzzling hand and arm pains. Ergonomic modifications can help to control symptoms, but optimal health may require collaborative management incorporating psychosocial and psychological elements of illness.

  2. Nonspecific Arm Pain

    Directory of Open Access Journals (Sweden)

    Ali Moradi

    2013-12-01

    Full Text Available   Nonspecific activity-related arm pain is characterized by an absence of objective physical findings and symptoms that do not correspond with objective pathophysiology. Arm pain without strict diagnosis is often related to activity, work-related activity in particular, and is often seen in patients with physically demanding work. Psychological factors such as catastrophic thinking, symptoms of depression, and heightened illness concern determine a substantial percentage of the disability associated with puzzling hand and arm pains. Ergonomic modifications can help to control symptoms, but optimal health may require collaborative management incorporating psychosocial and psychological elements of illness.

  3. Arms Trafficking and Colombia

    Science.gov (United States)

    2003-01-01

    Brasil , February 20, 2001. 20 Arms Trafficking and Colombia chased, when and how they were transferred to the guerrillas or paramilitaries, or through...Mercado Blanco De Armas,” 1999, p. 44. 31Franco, Ilimar, “Pf to Block Farc Supply Routes in Amazon,” Jornal do Brasil , August 20, 1999. 26 Arms...Forces Mobilize in Response to Farc,” Sao Paulo Veja, November 10, 1999. 43“Arms Trafficking to Colombia Increases,” El Comercio , August 23, 2000

  4. A Post-Docking Role of Synaptotagmin 1-C2B Domain Bottom Residues R398/399 in Mouse Chromaffin Cells

    DEFF Research Database (Denmark)

    Kedar, Girish H; Munch, Anders S; van Weering, Jan R T;

    2015-01-01

    Synaptotagmin-1 (Syt1) is the principal Ca2+ sensor for vesicle fusion and is also essential for vesicle docking in chromaffin cells. Docking depends on interactions of the Syt1-C2B domain with the t-SNARE SNAP25/Syntaxin1 complex and/or plasma membrane phospholipids. Here, we investigated the role...... of the positively charged “bottom” region of the C2B domain, proposed to help crosslink membranes, in vesicle docking and secretion in mouse chromaffin cells and in cell-free assays. We expressed a double mutation shown previously to interfere with lipid mixing between proteoliposomes and with synaptic transmission...... mutants. Finally, overexpressing the RQ-mutant in wild type cells produced no effect on either docking or secretion. We conclude that the positively charged bottom region in the C2B domain—and, by inference, Syt1-mediated membrane crosslinking—is required for triggering fusion, but not for docking...

  5. Development and Control of the Naval Postgraduate School Planar Autonomous Docking Simulator (NPADS)

    Science.gov (United States)

    Porter, Robert D.

    2002-09-01

    The objective of this thesis was to design, construct and develop the initial autonomous control algorithm for the NPS Planar Autonomous Docking Simulator (NPADS) The effort included hardware design, fabrication, installation and integration; mass property determination; and the development and testing of control laws utilizing MATLAB and Simulink for modeling and LabView for NPADS control, The NPADS vehicle uses air pads and a granite table to simulate a 2-D, drag-free, zero-g space environment, It is a completely self-contained vehicle equipped with eight cold-gas, bang-bang type thrusters and a reaction wheel for motion control, A 'star sensor' CCD camera locates the vehicle on the table while a color CCD docking camera and two robotic arms will locate and dock with a target vehicle, The on-board computer system leverages PXI technology and a single source, simplifying systems integration, The vehicle is powered by two lead-acid batteries for completely autonomous operation, A graphical user interface and wireless Ethernet enable the user to command and monitor the vehicle from a remote command and data acquisition computer. Two control algorithms were developed and allow the user to either control the thrusters and reaction wheel manually or simply specify a desired location and rotation angle,

  6. Low-Impact Mating System for Docking Spacecraft

    Science.gov (United States)

    Lewis, James L.; Robertson, Brandan; Carroll, Monty B.; Le, Thang; Morales, Ray

    2008-01-01

    A document describes a low-impact mating system suitable for both docking (mating of two free-flying spacecraft) and berthing (in which a robot arm in one spacecraft positions an object for mating with either spacecraft). The low-impact mating system is fully androgynous: it mates with a copy of itself, i.e., all spacecraft and other objects to be mated are to be equipped with identical copies of the system. This aspect of the design helps to minimize the number of unique parts and to standardize and facilitate mating operations. The system includes a closed-loop feedback control subsystem that actively accommodates misalignments between mating spacecraft, thereby attenuating spacecraft dynamics and mitigating the need for precise advance positioning of the spacecraft. The operational characteristics of the mating system can be easily configured in software, during operation, to enable mating of spacecraft having various masses, center-of-gravity offsets, and closing velocities. The system design provides multi-fault tolerance for critical operations: for example, to ensure unmating at a critical time, a redundant unlatching mechanism and two independent pyrotechnic release subsystems are included.

  7. An Elastica Arm Scale

    CERN Document Server

    Bosi, F; Corso, F Dal; Bigoni, D

    2015-01-01

    The concept of 'deformable arm scale' (completely different from a traditional rigid arm balance) is theoretically introduced and experimentally validated. The idea is not intuitive, but is the result of nonlinear equilibrium kinematics of rods inducing configurational forces, so that deflection of the arms becomes necessary for the equilibrium, which would be impossible for a rigid system. In particular, the rigid arms of usual scales are replaced by a flexible elastic lamina, free of sliding in a frictionless and inclined sliding sleeve, which can reach a unique equilibrium configuration when two vertical dead loads are applied. Prototypes realized to demonstrate the feasibility of the system show a high accuracy in the measure of load within a certain range of use. It is finally shown that the presented results are strongly related to snaking of confined beams, with implications on locomotion of serpents, plumbing, and smart oil drilling.

  8. Arm CT scan

    Science.gov (United States)

    ... scanners can perform the exam without stopping.) A computer creates separate images of the arm area, called ... M. is also a founding member of Hi-Ethics and subscribes to the principles of the Health ...

  9. Worldwide Report, Arms Control

    Science.gov (United States)

    2007-11-02

    world war, a nuclear inferno , for over 40 years. A sober assessment of the situation in world politics was conducted at the meet- ing of the...there is success in stopping the arms race, or those forces accelerating the arms race and driving humanity to the edge of a nuclear inferno will gain...dialogue with all forces fighting against a nuclear inferno , affirmed by the Warsaw Pact countries, is being seen more and more as the only practicable

  10. Fully Flexible Docking of Medium Sized Ligand Libraries with RosettaLigand.

    Directory of Open Access Journals (Sweden)

    Samuel DeLuca

    Full Text Available RosettaLigand has been successfully used to predict binding poses in protein-small molecule complexes. However, the RosettaLigand docking protocol is comparatively slow in identifying an initial starting pose for the small molecule (ligand making it unfeasible for use in virtual High Throughput Screening (vHTS. To overcome this limitation, we developed a new sampling approach for placing the ligand in the protein binding site during the initial 'low-resolution' docking step. It combines the translational and rotational adjustments to the ligand pose in a single transformation step. The new algorithm is both more accurate and more time-efficient. The docking success rate is improved by 10-15% in a benchmark set of 43 protein/ligand complexes, reducing the number of models that typically need to be generated from 1000 to 150. The average time to generate a model is reduced from 50 seconds to 10 seconds. As a result we observe an effective 30-fold speed increase, making RosettaLigand appropriate for docking medium sized ligand libraries. We demonstrate that this improved initial placement of the ligand is critical for successful prediction of an accurate binding position in the 'high-resolution' full atom refinement step.

  11. Differential regulation of synaptic vesicle tethering and docking by UNC-18 and TOM-1

    Directory of Open Access Journals (Sweden)

    Elena O Gracheva

    2010-10-01

    Full Text Available The assembly of SNARE complexes between syntaxin, SNAP-25 and synaptobrevin is required to prime synaptic vesicles for fusion. Since Munc18 and tomosyn compete for syntaxin interactions, the interplay between these proteins is predicted to be important in regulating synaptic transmission. We explored this possibility, by examining genetic interactions between C. elegans unc-18(Munc18, unc-64(syntaxin and tom-1(tomosyn. We have previously demonstrated that unc-18 mutants have reduced synaptic transmission, whereas tom-1 mutants exhibit enhanced release. Here we show that the unc-18 mutant release defect is associated with loss of two morphologically distinct vesicle pools; those tethered within 25nm of the plasma membrane and those docked with the plasma membrane. In contrast, priming defective unc-13 mutants accumulate tethered vesicles, while docked vesicles are greatly reduced, indicating tethering is UNC-18-dependent and occurs in the absence of priming. C. elegans unc-64 mutants phenocopy unc-18 mutants, losing both tethered and docked vesicles, whereas overexpression of open syntaxin preferentially increases vesicle docking, suggesting UNC-18/closed syntaxin interactions are responsible for vesicle tethering. Given the competition between vertebrate tomosyn and Munc18, for syntaxin binding, we hypothesized that C. elegans TOM-1 may inhibit both UNC-18-dependent vesicle targeting steps. Consistent with this hypothesis, tom-1 mutants exhibit enhanced UNC-18 plasma membrane localization and a concomitant increase in both tethered and docked synaptic vesicles. Furthermore, in tom-1;unc-18 double mutants the docked, primed vesicle pool is preferentially rescued relative to unc-18 single mutants. Together these data provide evidence for the differential regulation of two vesicle targeting steps by UNC-18 and TOM-1 through competitive interactions with syntaxin

  12. Hello to Arms

    Science.gov (United States)

    2005-01-01

    This image highlights the hidden spiral arms (blue) that were discovered around the nearby galaxy NGC 4625 by the ultraviolet eyes of NASA's Galaxy Evolution Explorer. The image is composed of ultraviolet and visible-light data, from the Galaxy Evolution Explorer and the California Institute of Technology's Digitized Sky Survey, respectively. Near-ultraviolet light is colored green; far-ultraviolet light is colored blue; and optical light is colored red. As the image demonstrates, the lengthy spiral arms are nearly invisible when viewed in optical light while bright in ultraviolet. This is because they are bustling with hot, newborn stars that radiate primarily ultraviolet light. The youthful arms are also very long, stretching out to a distance four times the size of the galaxy's core. They are part of the largest ultraviolet galactic disk discovered so far. Located 31 million light-years away in the constellation Canes Venatici, NGC 4625 is the closest galaxy ever seen with such a young halo of arms. It is slightly smaller than our Milky Way, both in size and mass. However, the fact that this galaxy's disk is forming stars very actively suggests that it might evolve into a more massive and mature galaxy resembling our own. The armless companion galaxy seen below NGC 4625 is called NGC 4618. Astronomers do not know why it lacks arms but speculate that it may have triggered the development of arms in NGC 4625.

  13. Arm & Interarm Star Formation in Spiral Galaxies

    CERN Document Server

    Foyle, Kelly; Walter, Fabian; Leroy, Adam

    2010-01-01

    We investigate the relationship between spiral arms and star formation in the grand-design spirals NGC 5194 and NGC 628 and in the flocculent spiral NGC 6946. Filtered maps of near-IR (3.6 micron) emission allow us to identify "arm regions" that should correspond to regions of stellar mass density enhancements. The two grand-design spirals show a clear two-armed structure, while NGC 6946 is more complex. We examine these arm and interarm regions, looking at maps that trace recent star formation - far-ultraviolet (GALEX NGS) and 24 micron emission (Spitzer, SINGS) - and cold gas - CO (Heracles) and HI (Things). We find the star formation tracers and CO more concentrated in the spiral arms than the stellar 3.6 micron flux. If we define the spiral arms as the 25% highest pixels in the filtered 3.6 micron images, we find that the majority (60%) of star formation tracers occurs in the interarm regions; this result persists qualitatively even when considering the potential impact of finite data resolution and diffu...

  14. Autonomous Rendezvous and Docking Conference, volume 1

    Science.gov (United States)

    1990-01-01

    This document consists of the presentation submitted at the Autonomous Rendezvous and Docking (ARD) Conference. It contains three volumes: ARD hardware technology; ARD software technology; and ARD operations. The purpose of this conference is to identify the technologies required for an on orbit demonstration of the ARD, assess the maturity of these technologies, and provide the necessary insight for a quality assessment of the programmatic management, technical, schedule, and cost risks.

  15. Autonomous Rendezvous and Docking Conference, volume 3

    Science.gov (United States)

    1990-01-01

    This document consists of the presentation submitted at the Autonomous Rendezvous and Docking (ARD) Conference. The document contains three volumes: ARD hardware technology; ARD software technology; and ARD operations. The purpose of this conference is to identify the technologies required for an on orbit demonstration of ARD, assess the maturity of these technologies, and provide the necessary insight for a quality assessment of programmatic management, technical, schedule, and cost risks.

  16. Combined Immunodeficiency Associated with DOCK8 Mutations

    Science.gov (United States)

    Zhang, Qian; Davis, Jeremiah C.; Lamborn, Ian T.; Freeman, Alexandra F.; Jing, Huie; Favreau, Amanda J.; Matthews, Helen F.; Davis, Joie; Turner, Maria L.; Uzel, Gulbu; Holland, Steven M.; Su, Helen C.

    2010-01-01

    BACKGROUND Recurrent sinopulmonary and cutaneous viral infections with elevated serum levels of IgE are features of some variants of combined immunodeficiency. The genetic causes of these variants are unknown. METHODS We collected longitudinal clinical data on 11 patients from eight families who had recurrent sinopulmonary and cutaneous viral infections. We performed comparative genomic hybridization arrays and targeted gene sequencing. Variants with predicted loss-of-expression mutations were confirmed by means of a quantitative reverse-transcriptase –polymerase-chain-reaction assay and immunoblotting. We evaluated the number and function of lymphocytes with the use of in vitro assays and flow cytometry. RESULTS Patients had recurrent otitis media, sinusitis, and pneumonias; recurrent Staphylococcus aureus skin infections with otitis externa; recurrent, severe herpes simplex virus or herpes zoster infections; extensive and persistent infections with molluscum contagiosum; and human papillomavirus infections. Most patients had severe atopy with anaphylaxis; several had squamous-cell carcinomas, and one had T-cell lymphoma –leukemia. Elevated serum IgE levels, hypereosinophilia, low numbers of T cells and B cells, low serum IgM levels, and variable IgG antibody responses were common. Expansion in vitro of activated CD8 T cells was impaired. Novel homozygous or compound heterozygous deletions and point mutations in the gene encoding the dedicator of cytokinesis 8 protein (DOCK8) led to the absence of DOCK8 protein in lymphocytes. CONCLUSIONS Autosomal recessive DOCK8 deficiency is associated with a novel variant of combined immunodeficiency. PMID:19776401

  17. Arm To Arm Interface Using Embedded C

    Directory of Open Access Journals (Sweden)

    Mohanraj.C

    2013-02-01

    Full Text Available Embedded systems are the most emerging field in these recent years. In this paper a different number of ARM processors (LPC2148 and LPC2378 are interconnected using C for distributed services. N numbers of processors are connected as the network and each processing devices are interlinked with each other, so that the each data that is processed by the devices and it can be used by the other device to activate their entire process. All the processed data’s are communicated to other device through Xbee interface card. LPC2148 and LPC2378 ARM processors are used in this prototype and winXtalk is used as a software terminal window. In this paper, the ultimate benefits of multiple processor interactions related to the embedded applications and design issues of processor interconnection are discussed. The features of multiple processor interaction in inter process communication and executions of embedded multitasking are also discussed. In modern embedded computing platform, embedded processor used in various applications like home automation, industrial control, medical system, access control, etc. In this paper, using embedded processor interactions, the several data communication is established.

  18. Complexity

    CERN Document Server

    Gershenson, Carlos

    2011-01-01

    The term complexity derives etymologically from the Latin plexus, which means interwoven. Intuitively, this implies that something complex is composed by elements that are difficult to separate. This difficulty arises from the relevant interactions that take place between components. This lack of separability is at odds with the classical scientific method - which has been used since the times of Galileo, Newton, Descartes, and Laplace - and has also influenced philosophy and engineering. In recent decades, the scientific study of complexity and complex systems has proposed a paradigm shift in science and philosophy, proposing novel methods that take into account relevant interactions.

  19. Conceptual design of the hot cell facility universal docking station at ITER

    Energy Technology Data Exchange (ETDEWEB)

    Dammann, A., E-mail: alexis.dammann@iter.org [ITER Organization, CS 90 046, 13067 St Paul Lez Durance Cedex (France); Benchikhoune, M.; Friconneau, J.P.; Ivanov, V. [ITER Organization, CS 90 046, 13067 St Paul Lez Durance Cedex (France); Lemee, A. [SOGETI High Tech, 180 Rue Rene Descartes, 13851 Aix en Provence (France); Martins, J.P. [ITER Organization, CS 90 046, 13067 St Paul Lez Durance Cedex (France); Tamassy, G. [SOGETI High Tech, 180 Rue Rene Descartes, 13851 Aix en Provence (France)

    2011-10-15

    Between main shutdowns of the ITER machine, in-vessel components and Iter Remote Maintenance System (IRMS) are transferred between the Tokamak complex and the Hot Cell Facility using different types of sealed casks. Transfer Casks have different physical interfaces with the Vacuum Vessel, which need to be the same at the docking stations of the HCF. It means that in-vessel components and IRMS are cleaned in the same cells, which is in fact not convenient. Furthermore, logistic studies showed that the use rate of the cells is very inhomogeneous. In order to have dedicated cell for decontamination of Remote Handling tools, in order to increase the operability efficiency and to removes the hot cell docking operation from the critical path, the concept of a universal docking station has been investigated. Based on an existing design, the work was focused on a review of requirements, the re-design and the integration within the HCF layout. The universal docking station has been proposed and is now integrated in HCF design.

  20. Molecular docking of bacosides with tryptophan hydroxylase: a model to understand the bacosides mechanism.

    Science.gov (United States)

    Rajathei, David Mary; Preethi, Jayakumar; Singh, Hemant K; Rajan, Koilmani Emmanuvel

    2014-08-01

    Tryptophan hydroxylase (TPH) catalyses l-tryptophan into 5-hydroxy-l-tryptophan, which is the first and rate-limiting step of serotonin (5-HT) biosynthesis. Earlier, we found that TPH2 up-regulated in the hippocampus of postnatal rats after the oral treatment of Bacopa monniera leaf extract containing the active compound bacosides. However, the knowledge about the interactions between bacosides with TPH is limited. In this study, we take advantage of in silico approach to understand the interaction of bacoside-TPH complex using three different docking algorithms such as HexDock, PatchDock and AutoDock. All these three algorithms showed that bacoside A and A3 well fit into the cavity consists of active sites. Further, our analysis revealed that major active compounds bacoside A3 and A interact with different residues of TPH through hydrogen bond. Interestingly, Tyr235, Thr265 and Glu317 are the key residues among them, but none of them are either at tryptophan or BH4 binding region. However, its note worthy to mention that Tyr 235 is a catalytic sensitive residue, Thr265 is present in the flexible loop region and Glu317 is known to interacts with Fe. Interactions with these residues may critically regulate TPH function and thus serotonin synthesis. Our study suggested that the interaction of bacosides (A3/A) with TPH might up-regulate its activity to elevate the biosynthesis of 5-HT, thereby enhances learning and memory formation.

  1. The DOCK protein sponge binds to ELMO and functions in Drosophila embryonic CNS development.

    Directory of Open Access Journals (Sweden)

    Bridget Biersmith

    Full Text Available Cell morphogenesis, which requires rearrangement of the actin cytoskeleton, is essential to coordinate the development of tissues such as the musculature and nervous system during normal embryonic development. One class of signaling proteins that regulate actin cytoskeletal rearrangement is the evolutionarily conserved CDM (C. elegansCed-5, human DOCK180, DrosophilaMyoblast city, or Mbc family of proteins, which function as unconventional guanine nucleotide exchange factors for the small GTPase Rac. This CDM-Rac protein complex is sufficient for Rac activation, but is enhanced upon the association of CDM proteins with the ELMO/Ced-12 family of proteins. We identified and characterized the role of Drosophila Sponge (Spg, the vertebrate DOCK3/DOCK4 counterpart as an ELMO-interacting protein. Our analysis shows Spg mRNA and protein is expressed in the visceral musculature and developing nervous system, suggesting a role for Spg in later embryogenesis. As maternal null mutants of spg die early in development, we utilized genetic interaction analysis to uncover the role of Spg in central nervous system (CNS development. Consistent with its role in ELMO-dependent pathways, we found genetic interactions with spg and elmo mutants exhibited aberrant axonal defects. In addition, our data suggests Ncad may be responsible for recruiting Spg to the membrane, possibly in CNS development. Our findings not only characterize the role of a new DOCK family member, but help to further understand the role of signaling downstream of N-cadherin in neuronal development.

  2. Scheduling Trucks in a Cross-Dock with Mixed Service Mode Dock Doors

    DEFF Research Database (Denmark)

    Bodnar, Peter; Azadeh, Kaveh; Koster, René de

    2015-01-01

    The problem considered in this paper is how to schedule inbound and outbound trucks subject to time windows at a multidoor cross-dock. Dock doors can either be dedicated to inbound or outbound trucks or be capable of handling both truck types. In addition, loads are allowed to be temporarily...... buffered to bridge the time between load arrival and departure. We minimize operational costs consisting of the cost of handling loads in temporary storage, as well as the cost of tardiness caused by processing outbound trucks after their respective due times. A mathematical model is derived...

  3. An information-theoretic classification of amino acids for the assessment of interfaces in protein-protein docking.

    Science.gov (United States)

    Jardin, Christophe; Stefani, Arno G; Eberhardt, Martin; Huber, Johannes B; Sticht, Heinrich

    2013-09-01

    Docking represents a versatile and powerful method to predict the geometry of protein-protein complexes. However, despite significant methodical advances, the identification of good docking solutions among a large number of false solutions still remains a difficult task. We have previously demonstrated that the formalism of mutual information (MI) from information theory can be adapted to protein docking, and we have now extended this approach to enhance its robustness and applicability. A large dataset consisting of 22,934 docking decoys derived from 203 different protein-protein complexes was used for an MI-based optimization of reduced amino acid alphabets representing the protein-protein interfaces. This optimization relied on a clustering analysis that allows one to estimate the mutual information of whole amino acid alphabets by considering all structural features simultaneously, rather than by treating them individually. This clustering approach is fast and can be applied in a similar fashion to the generation of reduced alphabets for other biological problems like fold recognition, sequence data mining, or secondary structure prediction. The reduced alphabets derived from the present work were converted into a scoring function for the evaluation of docking solutions, which is available for public use via the web service score-MI: http://score-MI.biochem.uni-erlangen.de.

  4. A Review: Mathematical Modles for Cross Docking Planning

    Directory of Open Access Journals (Sweden)

    Dwi Agustina

    2010-09-01

    Full Text Available This paper provides a comprehensive literature review of mathematical models in cross docking planning. From the reviews, the models are classified in three different levels regarding its decisions level which are operational, tactical, and strategic level. The researches in operational level are mainly related to develop model in scheduling, dock door assignment, transhipment problem, vehicle routing, and product allocation. For tactical and strategic level, the researches are mainly proposing model to design the layout and the network of cross docking respectively. The contribution of this paper is to realize the gaps of knowledge in strategic, tactical and operational levels and point out the future research directions in cross docking.

  5. JPRS Report, Arms Control

    Science.gov (United States)

    2007-11-02

    34military activities, whether in the armed forces, their civilian sectors, or in the ’defence’ indus- try". In another paper Professor Carl Sagan ...spurring the development of new weapons. Star Wars is a case in point. As Carl Sagan puts it, the idea is doomed: "SDI is ruinously expensive, it can

  6. Worldwide Report, Arms Control.

    Science.gov (United States)

    1985-08-12

    thai, in the long run one cannot oven tell to willy frandi’and fgon fahr . ’r’ho Soviets arc thus evoking the suspicion that they are playing dirty...material resources and the knowledge of scientists in combatting diseases , if the resources were spent on it that are taken up by the arms race

  7. JPRS Report, Arms Control.

    Science.gov (United States)

    2007-11-02

    Joint-Stock Company"] [Text] A constituent conference of the "Ural- Kosmos " closed joint-stock company [aktsionernoye obshchestvo zakrytogo tipa] has...due to be destroyed under arms cuts. Their warheads will be replaced by communications satellites. The founders of the "Ural- Kosmos " company note

  8. Worldwide Report, Arms Control

    Science.gov (United States)

    2007-11-02

    Soviet Laser Expert (N. G. Bazov Interview; CAMBIO 16, 11-18 Feb 85) 86 Unnamed General Urges French ’Star Wars’ Effort (Hoplites; LE MONDE, 6...1024 85 JPRS-TAC-85-002 1 April 1985 SPACE ARMS SPANISH MAGAZINE CITES SOVIET LASER EXPERT PM211619 [Editorial Report] Madrid CAMBIO 16 in Spanish

  9. Worldwide Report, Arms Control

    Science.gov (United States)

    1985-12-31

    Bonn RHEINISCHER MERKUR /CHRIST UND WELT, 12 Oct 85) . 14 GDR Commentary on Geneva Talks (Various sources,various dates) 19 Military...USSR GENEVA TALKS FRG DEFENSE UNDERSECRETARY SUPPORTS U.S. VIEW ON ARMS CONTROL Bonn RHEINISCHER MERKUR /CHRIST UND WELT in German 12 Oct 85 p 3

  10. Worldwide Report, Arms Control

    Science.gov (United States)

    2007-11-02

    like tired runners exposed to the sights of millions of viewers. The fear of oxygen starvation was handled by the U.S. President on several levels...and to present the U.S. attitudes as the only way out of the maze of the arms race. It is an attempt to push through the old principles of U.S

  11. Modelling of biomolecular complexes by data-driven docking

    NARCIS (Netherlands)

    Dijk, A.D.J. van

    2006-01-01

    Proteins play a major role in biology by interacting with each other and with other biomolecules. The study of these interactions is of fundamental importance to understand cellular processes, and this could be a key towards understanding mechanisms of diseases and possible development of drugs. As

  12. Autonomous Rendezvous and Docking Conference, volume 2

    Science.gov (United States)

    1990-01-01

    Autonomous Rendezvous and Docking (ARD) will be a requirement for future space programs. Clear examples include satellite servicing, repair, recovery, and reboost in the near term, and the longer range lunar and planetary exploration programs. ARD will permit more aggressive unmanned space activities, while providing a valuable operational capability for manned missions. The purpose of the conference is to identify the technologies required for an on-orbit demonstration of ARD, assess the maturity of those technologies, and provide the necessary insight for a quality assessment of programmatic management, technical, schedule, and cost risks.

  13. [Study on anti-hyperlipidemia mechanism of high frequency herb pairs by molecular docking method].

    Science.gov (United States)

    Jiang, Lu-di; He, Yu-su; Chen, Xi; Tao, Ou; Li, Gong-Yu; Zhang, Yan-ling

    2015-06-01

    Traditional Chinese medicine (TCM) has definitely clinical effect in treating hyperlipidemia, but the action mechanism still need to be explored. Based on consulting Chinese Pharmacopoeia (2010), all the lipid-lowering Chinese patent medicines were analyzed by associated rules data mining method to explore high frequency herb pairs. The top three couplet medicines with high support degree were Puerariae Lobatae Radix-Crataegi Fructus, Salviae Miltiorrhizae Radix et Rhizoma-Crataegi Fructus, and Polygoni Multiflori Radix-Crataegi Fructus. The 20 main ingredients were selected from the herb pairs and docked with 3 key hyperlipidemia targets, namely 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), peroxisome proliferator activated receptor-α (PPAR-α ) and niemann-pick C1 like 1 (NPC1L1) to further discuss the molecular mechanism of the high frequency herb pairs, by using the docking program, LibDock. To construct evaluation rules for the ingredients of herb pairs, the root-mean-square deviation (RMSD) value between computed and initial complexes was first calculated to validate the fitness of LibDock models. Then, the key residues were also confirmed by analyzing the interactions of those 3 proteins and corresponding marketed drugs. The docking results showed that hyperin, puerarin, salvianolic acid A and polydatin can interact with two targets, and the other five compounds may be potent for at least one of the three targets. In this study, the multi-target effect of high frequency herb pairs for lipid-lowering was discussed on the molecular level, which can help further researching new multi-target anti-hyperlipidemia drug.

  14. DECK: Distance and environment-dependent, coarse-grained, knowledge-based potentials for protein-protein docking

    Directory of Open Access Journals (Sweden)

    Vakser Ilya A

    2011-07-01

    Full Text Available Abstract Background Computational approaches to protein-protein docking typically include scoring aimed at improving the rank of the near-native structure relative to the false-positive matches. Knowledge-based potentials improve modeling of protein complexes by taking advantage of the rapidly increasing amount of experimentally derived information on protein-protein association. An essential element of knowledge-based potentials is defining the reference state for an optimal description of the residue-residue (or atom-atom pairs in the non-interaction state. Results The study presents a new Distance- and Environment-dependent, Coarse-grained, Knowledge-based (DECK potential for scoring of protein-protein docking predictions. Training sets of protein-protein matches were generated based on bound and unbound forms of proteins taken from the DOCKGROUND resource. Each residue was represented by a pseudo-atom in the geometric center of the side chain. To capture the long-range and the multi-body interactions, residues in different secondary structure elements at protein-protein interfaces were considered as different residue types. Five reference states for the potentials were defined and tested. The optimal reference state was selected and the cutoff effect on the distance-dependent potentials investigated. The potentials were validated on the docking decoys sets, showing better performance than the existing potentials used in scoring of protein-protein docking results. Conclusions A novel residue-based statistical potential for protein-protein docking was developed and validated on docking decoy sets. The results show that the scoring function DECK can successfully identify near-native protein-protein matches and thus is useful in protein docking. In addition to the practical application of the potentials, the study provides insights into the relative utility of the reference states, the scope of the distance dependence, and the coarse-graining of

  15. Response surface methodology in drug design: A case study on docking analysis of a potent antifungal fluconazole.

    Science.gov (United States)

    Bohlooli, Fatemeh; Sepehri, Saghi; Razzaghi-Asl, Nima

    2017-04-01

    Molecular docking is a valuable in silico technique for discovery/design of bioactive compounds. A current challenge within docking simulations is the incorporation of receptor flexibility. A useful strategy toward solving such problem would be the docking of a typical ligand into the multiple conformations of the target. In this study, a multifactor response surface model was constructed to estimate the AutoDock based binding free energy of fluconazole within multiple conformations of 14α-demethylase (CYP51) (cross docking) as a validated antifungal target. On the basis of developed models, individual and interactive effects of important experimental parameters on cross docking of fluconazole were elucidated. For this purpose, a set of high-resolution holo crystallographic structures from CYP51 of human pathogen Trypanosoma cruzi were retrieved to statistically model the binding mode and affinity of fluconazole. The changes of AutoDock binding free energy for the complexes of CYP51-fluconazole were elucidated with the simultaneous variations of six independent variables including grid size, grid spacing, number of genetic algorithm (GA) runs, maximum number of energy evaluations, torsion degrees for ligand and quaternion degrees for ligand. It was revealed that grid spacing (distance between adjacent grid points) and maximum number of energy evaluations were two significant model terms. It was also revealed that grid size, torsion degrees for ligand and quaternion degrees for ligand had insignificant effects on estimated binding energy while the effect of GA runs was non-significant. The interactive effect of "torsion degrees for ligand" with number of GA runs was found to be the significant factor. Other important interactive effects were the interaction of "number of GA runs" with "grid spacing" and "number of energy evaluations" with "grid size". Furthermore; results of modeling studies within several CYP51 conformations exhibited that "number of GA runs" and

  16. Modernization of African Armed Forces

    DEFF Research Database (Denmark)

    Mandrup, Thomas

    2015-01-01

    Concept paper framing the debate at the Dakar Forum Workshop on Modernization of Armed forces in Africa.......Concept paper framing the debate at the Dakar Forum Workshop on Modernization of Armed forces in Africa....

  17. A docking approach to the study of copper trafficking proteins: interaction between metallochaperones and soluble domains of copper ATPases

    NARCIS (Netherlands)

    Arnesano, F.; Banci, L.; Bertini, I.; Bonvin, A.M.J.J.

    2004-01-01

    A structural model of the transient complex between the yeast copper chaperone Atx1 and the first soluble domain of the copper transporting ATPase Ccc2 was obtained with HADDOCK, combining NMR chemical shift mapping information with in silico docking. These two proteins are involved in copper traffi

  18. Octopus-inspired multi-arm robotic swimming.

    Science.gov (United States)

    Sfakiotakis, M; Kazakidi, A; Tsakiris, D P

    2015-05-13

    The outstanding locomotor and manipulation characteristics of the octopus have recently inspired the development, by our group, of multi-functional robotic swimmers, featuring both manipulation and locomotion capabilities, which could be of significant engineering interest in underwater applications. During its little-studied arm-swimming behavior, as opposed to the better known jetting via the siphon, the animal appears to generate considerable propulsive thrust and rapid acceleration, predominantly employing movements of its arms. In this work, we capture the fundamental characteristics of the corresponding complex pattern of arm motion by a sculling profile, involving a fast power stroke and a slow recovery stroke. We investigate the propulsive capabilities of a multi-arm robotic system under various swimming gaits, namely patterns of arm coordination, which achieve the generation of forward, as well as backward, propulsion and turning. A lumped-element model of the robotic swimmer, which considers arm compliance and the interaction with the aquatic environment, was used to study the characteristics of these gaits, the effect of various kinematic parameters on propulsion, and the generation of complex trajectories. This investigation focuses on relatively high-stiffness arms. Experiments employing a compliant-body robotic prototype swimmer with eight compliant arms, all made of polyurethane, inside a water tank, successfully demonstrated this novel mode of underwater propulsion. Speeds of up to 0.26 body lengths per second (approximately 100 mm s(-1)), and propulsive forces of up to 3.5 N were achieved, with a non-dimensional cost of transport of 1.42 with all eight arms and of 0.9 with only two active arms. The experiments confirmed the computational results and verified the multi-arm maneuverability and simultaneous object grasping capability of such systems.

  19. ICRESH-ARMS 2015 Conference

    CERN Document Server

    Ahmadi, Alireza; Verma, Ajit; Varde, Prabhakar

    2016-01-01

    Containing selected papers from the ICRESH-ARMS 2015 conference in Lulea, Sweden, collected by editors with years of experiences in Reliability and maintenance modeling, risk assessment, and asset management, this work maximizes reader insights into the current trends in Reliability, Availability, Maintainability and Safety (RAMS) and Risk Management. Featuring a comprehensive analysis of the significance of the role of RAMS and Risk Management in the decision making process during the various phases of design, operation, maintenance, asset management and productivity in Industrial domains, these proceedings discuss key issues and challenges in the operation, maintenance and risk management of complex engineering systems and will serve as a valuable resource for those in the field.

  20. ARM User Survey Report

    Energy Technology Data Exchange (ETDEWEB)

    Roeder, LR

    2010-06-22

    The objective of this survey was to obtain user feedback to, among other things, determine how to organize the exponentially growing data within the Atmospheric Radiation Measurement (ARM) Climate Research Facility, and identify users’ preferred data analysis system. The survey findings appear to have met this objective, having received approximately 300 responses that give insight into the type of work users perform, usage of the data, percentage of data analysis users might perform on an ARM-hosted computing resource, downloading volume level where users begin having reservations, opinion about usage if given more powerful computing resources (including ability to manipulate data), types of tools that would be most beneficial to them, preferred programming language and data analysis system, level of importance for certain types of capabilities, and finally, level of interest in participating in a code-sharing community.

  1. A hierarchical method for molecular docking using cloud computing.

    Science.gov (United States)

    Kang, Ling; Guo, Quan; Wang, Xicheng

    2012-11-01

    Discovering small molecules that interact with protein targets will be a key part of future drug discovery efforts. Molecular docking of drug-like molecules is likely to be valuable in this field; however, the great number of such molecules makes the potential size of this task enormous. In this paper, a method to screen small molecular databases using cloud computing is proposed. This method is called the hierarchical method for molecular docking and can be completed in a relatively short period of time. In this method, the optimization of molecular docking is divided into two subproblems based on the different effects on the protein-ligand interaction energy. An adaptive genetic algorithm is developed to solve the optimization problem and a new docking program (FlexGAsDock) based on the hierarchical docking method has been developed. The implementation of docking on a cloud computing platform is then discussed. The docking results show that this method can be conveniently used for the efficient molecular design of drugs.

  2. Layout and control policies for cross docking operations

    NARCIS (Netherlands)

    Vis, Iris F. A.; Roodbergen, Kees Jan

    2011-01-01

    Many supply chains strive to shorten the time between a customer's order and the actual delivery of the ordered goods. Cross docking is one of the options to reduce these response times. Cross docking facilities are dynamic environments where products arrive and leave the same day. To deal with thes

  3. Kiikuv maja / Anu Arm

    Index Scriptorium Estoniae

    Arm, Anu

    2006-01-01

    Eesti Kunstiakadeemia esimese kursuse arhitektuuriüliõpilaste II semestri töö. Juhendaja arhitekt Andres Alver, ehitamise Pedaspeale organiseeris suvepraktika juhendaja arhitekt Jaan Tiidemann. Autor Anu Arm, kaasa töötasid ja valmis ehitasid: Ott Alver, Maarja Elm, Mari Hunt, Alvin Järving, Marten Kaevats, Riho Kerge, Reedik Poopuu, Anu Põime, Helen Rebane, Kaisa Saarva, Martin Tago, Reet Volt. Valmis: 19. VIII 2006

  4. JPRS Report, Arms Control

    Science.gov (United States)

    2007-11-02

    SINMUN in Korean 19 Jan 90 p 2 [ Editorial : "Arms Reduction Amid East-West Reconcil- iation"] [Text] It appears that with the end of cold-war, the...Navigation Radar Deployment PY1701143090 La Paz La Red Panamericana in Spanish 1130 GMT 17 Jan 90 [Text] Aeronautics Minister Luis Gonzales...airspace and that it can guarantee our sovereignty. Aeronautics Military Under Secretary Installed PY1701125290 La Paz La Red Panamericana in

  5. Worldwide Report, Arms Control.

    Science.gov (United States)

    2007-11-02

    Soviet violations, the Pentagon and the White House ended up in mush . Nevertheless, armed with mush as evidence, the American secretary of...YORK TIMES calling anti-Soviet charges mush is out- numbered by thousands of statements on radio and television, speeches before various...audiences, and articles in newspapers and magazines where that same mush is used as a serious argument. USSR Complying Treaties LD120557 Moscow

  6. Worldwide Report, Arms Control

    Science.gov (United States)

    2007-11-02

    Service, Springfield, Virginia 22161. In order- ing, it is recommended that the JPRS number, title, date and author, if applicable, of publication be...Road, Arlington, Virginia 22201. JPRS-TAC-86-025 14 March 1986 WORLDWIDE REPORT ARMS CONTROL CONTENTS U.S.-USSR GENEVA TALKS, USSR: Possibility for...34Vreyma" newscast] [Excerpts] A Moscow premiere. Our correspondent reports: The audience is hurrying to a premiere at the Moscow Satire Theater. What

  7. PERANCANGAN FLOATING DOCK UNTUK DAERAH PERAIRAN PELABUHAN KOTA TEGAL

    Directory of Open Access Journals (Sweden)

    Kiryanto Kiryanto

    2013-06-01

    Full Text Available Floating dock merupakan bangunan air sebagai tempat reparasi kapal yang dinilai cukup efisien dalam pembangunannya karena tidak membutuhkan dana yang terlalu mahal. Di sektor indusrti perkapalan kota tegal sudah memiliki galangan dan dock reparasi kapal yang cukup berkembang.  Ide perancangan floating dock ini dirancang sebagai alternatif baru pelayanan reparasi kapal. Perancangan floating dock ini juga memperhatikan dengan detail kapasitas kapal – kapal yang pernah melakukan repararasi di sekitar galangan di Kota Tegal agar ditemukan ukuran utama floating dock yang tepat. Dari Kapasitas kapal yang ada dan berdasarkan metode perbandingan ukuran beberapa floating dock, maka ditemukan ukuran utama yang tepat untuk menampung kebutuhan pelayanan reparasi kapal yaitu LOA = 136,37 m, Lpt = 114.80 m, Bmax = 36,40 m, Bmd: 30,80 m, Tmin = 0,86 m, Tmax = 1,58 m, Hpt = 2,10 m, HOA = 9,60 m. Berdasarkan perhitungan ditemukan juga Ton Lifting Capacity (TLC sebesar 3000 ton. Perancangan menggunakan software perkapalan yaitu dengan menggunakan AutoCad, Delftship, Maxsurf dan Hidromax. Dengan analisa stabilitas menggunakan software Hidromax diketahui bahwa floating dock ini mampu memiliki stabilitas yang baik dengan 4 kondisi yang semua memenuhi criteria  International Maritime Organisation (IMO. Perancangan floating dock ini juga menghitung analisa ekonomis dan investasi. Dari rekapitulasi dana investasi pembangunan floating dock yaitu sebesar Rp.136.622.888.000,00 dengan nilai kembali atau break even point selama 10 tahun dengan modal sendiri, 14 tahun dengan 50% modal sendiri dan 50 % pinjaman bank, dan break event point 18 tahun untuk dana pembangunan floating dock yang berasal dari 100 % pinjaman bank

  8. Analysis and Ranking of Protein-Protein Docking Models Using Inter-Residue Contacts and Inter-Molecular Contact Maps

    KAUST Repository

    Oliva, Romina

    2015-07-01

    In view of the increasing interest both in inhibitors of protein-protein interactions and in protein drugs themselves, analysis of the three-dimensional structure of protein-protein complexes is assuming greater relevance in drug design. In the many cases where an experimental structure is not available, protein-protein docking becomes the method of choice for predicting the arrangement of the complex. However, reliably scoring protein-protein docking poses is still an unsolved problem. As a consequence, the screening of many docking models is usually required in the analysis step, to possibly single out the correct ones. Here, making use of exemplary cases, we review our recently introduced methods for the analysis of protein complex structures and for the scoring of protein docking poses, based on the use of inter-residue contacts and their visualization in inter-molecular contact maps. We also show that the ensemble of tools we developed can be used in the context of rational drug design targeting protein-protein interactions.

  9. Comparing Evolutionary Programs and Evolutionary Pattern Search Algorithms: A Drug Docking Application

    Energy Technology Data Exchange (ETDEWEB)

    Hart, W.E.

    1999-02-10

    Evolutionary programs (EPs) and evolutionary pattern search algorithms (EPSAS) are two general classes of evolutionary methods for optimizing on continuous domains. The relative performance of these methods has been evaluated on standard global optimization test functions, and these results suggest that EPSAs more robustly converge to near-optimal solutions than EPs. In this paper we evaluate the relative performance of EPSAs and EPs on a real-world application: flexible ligand binding in the Autodock docking software. We compare the performance of these methods on a suite of docking test problems. Our results confirm that EPSAs and EPs have comparable performance, and they suggest that EPSAs may be more robust on larger, more complex problems.

  10. Studies on Pidotimod Enantiomers With Chiralpak-IA: Crystal Structure, Thermodynamic Parameters and Molecular Docking.

    Science.gov (United States)

    Dou, Xiaorui; Su, Xin; Wang, Yue; Chen, Yadong; Shen, Weiyang

    2015-11-01

    Pidotimod, a synthetic dipeptide, has two chiral centers with biological and immunological activity. Its enantiomers were characterized by x-ray crystallographic analysis. A chiral stationary phase (CSP) Chiralpak-IA based on amylose derivatized with tris-(3, 5-dimethylphenyl carbamate) was used to separate pidotimod enantiomers. The mobile phase was prepared in a ratio of 35:65:0.2 of methyl-tert-butyl-ether and acetonitrile trifluoroaceticacid. In addition, thermodynamics and molecular docking methods were used to explain the enantioseparation mechanism by Chiralpak-IA. Thermodynamic studies were carried out from 10 to 45 °C. In general, both retention and enantioselectivity decreased as the temperature increased. Thermodynamic parameters indicate that the interaction force between the pidotimod enantiomer (4S, 2'R) and IA CSP is stronger and their complex model is more stable. According to GOLD molecular docking simulation, Van der Waals force is the leading cause of pidotimod enantiomers separation by IA CSP.

  11. Giant Polymersome Protocells Dock with Virus Particle Mimics via Multivalent Glycan-Lectin Interactions

    Science.gov (United States)

    Kubilis, Artur; Abdulkarim, Ali; Eissa, Ahmed M.; Cameron, Neil R.

    2016-08-01

    Despite the low complexity of their components, several simple physical systems, including microspheres, coacervate droplets and phospholipid membrane structures (liposomes), have been suggested as protocell models. These, however, lack key cellular characteristics, such as the ability to replicate or to dock with extracellular species. Here, we report a simple method for the de novo creation of synthetic cell mimics in the form of giant polymeric vesicles (polymersomes), which are capable of behavior approaching that of living cells. These polymersomes form by self-assembly, under electroformation conditions, of amphiphilic, glycosylated block copolymers in aqueous solution. The glycosylated exterior of the resulting polymeric giant unilamellar vesicles (GUVs) allows their selective interaction with carbohydrate-binding receptor-functionalized particles, in a manner reminiscent of the cell-surface docking of virus particles. We believe that this is the first example of a simple protocell model displaying cell-like behavior through a native receptor-ligand interaction.

  12. Molecular docking and panicolytic effect of 8-prenylnaringenin in the elevated T-maze.

    Science.gov (United States)

    Bagatin, Mariane Cristovão; Tozatti, Camila Santos Suniga; Abiko, Layara Akemi; Yamazaki, Diego Alberto dos Santos; Silva, Priscila Rebeca Alves; Perego, Leonardo Martins; Audi, Elisabeth Aparecida; Seixas, Flavio Augusto Vicente; Basso, Ernani Abicht; Gauze, Gisele de Freitas

    2014-01-01

    The purpose of this study was to investigate the effects of the chronic administration of a racemic mixture of 8-prenylnaringenin (8-PN) on rats submitted to the elevated T-maze (ETM) model of generalized anxiety and panic disorders. The selective serotonin (SERT) reuptake inhibitor fluoxetine was used as a positive control. Rat locomotion was assessed in a circular arena following each drug treatment. The administration of racemic 8-PN for 21 d in rats increased one-way escape latencies from the ETM open arm, indicating a panicolytic effect. To evaluate the interactions of 8-PN with monoamine transporters, a docking study was performed for both the R and S configurations of 8-PN towards SERT, norepinephrine (NET) and dopamine transporters (DAT). The application of the docking protocol showed that (R)-8-PN provides greater affinity to all transporters than does the S enantiomer. This result suggests that enantiomer (R)-8-PN is the active form in the in vivo test of the racemic mixture.

  13. Autonomous sensor-based dual-arm satellite grappling

    Science.gov (United States)

    Wilcox, Brian; Tso, Kam; Litwin, Todd; Hayati, Samad; Bon, Bruce

    1989-01-01

    Dual-arm satellite grappling involves the integration of technologies developed in the Sensing and Perception (S&P) Subsystem for object acquisition and tracking, and the Manipulator Control and Mechanization (MCM) Subsystem for dual-arm control. S&P acquires and tracks the position, orientation, velocity, and angular velocity of a slowly spinning satellite, and sends tracking data to the MCM subsystem. MCM grapples the satellite and brings it to rest, controlling the arms so that no excessive forces or torques are exerted on the satellite or arms. A 350-pound satellite mockup which can spin freely on a gimbal for several minutes, closely simulating the dynamics of a real satellite is demonstrated. The satellite mockup is fitted with a panel under which may be mounted various elements such as line replacement modules and electrical connectors that will be used to demonstrate servicing tasks once the satellite is docked. The subsystems are housed in three MicroVAX II microcomputers. The hardware of the S&P Subsystem includes CCD cameras, video digitizers, frame buffers, IMFEX (a custom pipelined video processor), a time-code generator with millisecond precision, and a MicroVAX II computer. Its software is written in Pascal and is based on a locally written vision software library. The hardware of the MCM Subsystem includes PUMA 560 robot arms, Lord force/torque sensors, two MicroVAX II computers, and unimation pneumatic parallel grippers. Its software is written in C, and is based on a robot language called RCCL. The two subsystems are described and test results on the grappling of the satellite mockup with rotational rates of up to 2 rpm are provided.

  14. Systematic Protein-Protein Docking and Molecular Dynamics Studies of HIV-1 gp120 and CD4: Insights for New Drug Development

    Directory of Open Access Journals (Sweden)

    M. Rizman-Idid

    2011-12-01

    Full Text Available Background and the purpose of the study: The interactions between HIV-1 gp120 and mutated CD4 proteins were investigated in order to identify a lead structure for therapy based on competitive blocking of the HIV binding receptor for human T-cells. Crystal structures of HIV gp120-CD4 complexes reveal a close interaction of the virus receptor with CD4 Phe43, which is embedded in a pocket of the virus protein.Methods: This study applies computer simulations to determine the best binding of amino acid 43 CD4 mutants to HIV gp120. Besides natural CD4, three mutants carrying alternate aromatic residues His, Trp and Tyr at position 43 were investigated. Several docking programs were applied on isolated proteins based on selected crystal structures of gp120-CD4 complexes, as well as a 5 ns molecular dynamics study on the protein complexes. The initial structures were minimized in Gromacs to avoid crystal packing effects, and then subjected to docking experiments using AutoDock4, FireDock, ClusPro and ZDock. In molecular dynamics, the Gibbs free binding energy was calculated for the gp120-CD4 complexes. The docking outputs were analyzed on energy within the respective docking software.Results and conclusion: Visualization and hydrogen bonding analysis were performed using the Swiss-PdbViewer. Strong binding to HIV gp120 can be achieved with an extended aromatic group (Trp. However, the sterical demand of the interaction affects the binding kinetics. In conclusion, a ligand for an efficient blocking of HIV gp120 should involve an extended but conformational flexible aromatic group, i.e. a biphenyl. A docking study on biphenylalanine-43 confirms this expectation

  15. AES i ARM procesori

    Directory of Open Access Journals (Sweden)

    Danijela D. Protić

    2013-12-01

    Full Text Available Potreba za zaštitom informacija dovodi do velikih problema u izradi prenosivih uređaja kojima su limitirani snaga, memorija i energija. Ukoliko se takvim uređajima dodaju koprocesori, koji treba da obavljaju funkcije kriptozaštite, njihove se dimenzije povećavaju, pojavljuje se nefleksibilnost pa cena uređaja raste i do nekoliko puta. Na drugoj strani, algoritmi za zaštitu podataka su često memorijski zahtevni, a zbog velikog broja operacija koje je potrebno izvršavati u procesima šifrovanja i dešifrovanja, koprocesori često uspore rad osnovnog procesora. Za jedan od standarda za kriptozaštitu, AES, NIST je prihvatio Rijndaelov blokovski algoritam sa dužinom ulaznog i izlaznog bloka od 128 b, i dužinama šifarskog ključa od 128 b, 192 b i 256 b. Zbog karakteristika male potrošnje, 32-bitske arhitekture i brzog izvršavanja instrukcija, ARM procesori mogu da realizuju kriptozaštitu podataka, između ostalog i AES-om, a da ne opterete glavne procese u sistemima u kojima se koriste. Tehnologija ARM-a zaštićena je kao intelektualna svojina, pa je veliki broj proizvođača koristi za razvoj sopstvenih proizvoda, što je rezultovalo činjenicom da je u svetu proizvedeno preko 2 milijarde čipova koji su bazirani na ovoj tehnologiji. U radu su prikazane mogućnosti za poboljšanja u izvršenju algoritma AES primenom najnovijih verzija ARM procesora.

  16. Worldwide Report, Arms Control

    Science.gov (United States)

    2007-11-02

    put their feet on the table.... But that Is not the USSR’s problem. It is not for the USSR to teach the rules of etiquette vh~nh are broken in the...34 /12858 CSO: 5200/2634 • 138 - RELATED ISSUES LABOR PARTY DISTRICT CONGRESS: BAN NUCLEAR ARMED SHIPS Oslo AFTENPOSTEN in Norwegian 27 Jan 86 p 3 [Article...that countries which send warships into Norwegian ports should guarantee that these ships are not carry- ing nuclear weapons. The requirement would

  17. Docking Studies of Binding of Ethambutol to the C-Terminal Domain of the Arabinosyltransferase from Mycobacterium tuberculosis

    OpenAIRE

    Guillermo Salgado-Moran; Rodrigo Ramirez-Tagle; Daniel Glossman-Mitnik; Samuel Ruiz-Nieto; Pran Kishore-Deb; Marta Bunster; Francisco Lobos-Gonzalez

    2013-01-01

    The binding of ethambutol to the C-terminal domain of the arabinosyltransferase from Mycobacterium tuberculosis was studied. The analysis was performed using an in silico approach in order to find out, by docking calculations and energy descriptors, the conformer of Ethambutol that forms the most stable complex with the C-terminal domain of arabinosyltransferase. The complex shows that location of the Ethambutol coincides with the cocrystallization ligand position and that amino acid residu...

  18. Unenhanced spiral CT localization combined with C-arm in minimally invasive percutaneous nephrolithotomy(MPCNL) for complex renal calculi%非增强螺旋CT定位联合C臂微创经皮肾镜取石治疗复杂肾结石

    Institute of Scientific and Technical Information of China (English)

    蒋立城; 徐忠华; 张英晨; 王学廷; 丁吉阳; 程玉峰

    2012-01-01

    Objective To investigate the value of non-contrast-enhanced spiral CT-assistant localization combined with C-arm in the treatment of complex renal calculi by minimally invasive percutaneous nephrolithotomy ( mPCNL). Methods 50 patients with complex renal calculi underwent a non-contrast-enhanced spiral CT scan localization to simulate intraoperative posture before the operation and accepted the mPCNL treatment combined with C-arm (CT group). Another 38 patients with complex renal calculi who directly underwent puncture by C-arm localization were studied as the control group (C-arm group). Results In the CT group, the average number of punctures [(1.27 ±0.56) per side vs (2.28 ±1.19) punctures per side, P<0.01 ], channel building time[ (5.51 ±2.31)minutes per side vs (11.36 ± 6.15) minutes per side, P<0.01], C-arm usage counter[ (2.53 ±0. 77) vs (7.44 ± 1. 87), P <0.01 ] ,and X-ray exposure time for surgeons[ (0.32 ±0.73) minutes per side vs (0.53 ±0.28)minutes per side, P<0.05] and patients [ (0.43 ± 0.72) minutes per side vs (0.72 ± 0. 28) minutes per side, P < 0.01 ] were significantly lower than those of the C-arm group. Conclusion Non-contrast-enhanced spiral CT localization combined with C-arm can contribute to percutaneous renal puncture in the complex renal calculi treatment by m-PCNL, and effectively reduce the C-arm usage counter and intraoperative radiation exposure time.%目的 探讨非增强螺旋CT定位联合C型臂在复杂肾结石微创治疗中的应用价值.方法 对50例复杂肾结石患者术前模拟术中体位行螺旋CT扫描定位(CT组),术中联合C臂行微创经皮肾镜取石术,并与同期38例复杂肾结石直接C臂定位者(C臂组)进行比较.结果 CT组与C臂组比较,平均穿刺次数[(1.27±0.56)次/侧vs (2.28±1.19)次/侧,P<0.01]、通道建立时间[(5.51±2.31 )min/侧vs (11.36±6.15) min/侧,P<0.01]、C臂使用次数[(2.53±0.77)次/侧vs (7.44±1.87)次/侧,P<0.01]及医生

  19. Combining docking with pharmacophore filtering for improved virtual screening

    Directory of Open Access Journals (Sweden)

    Peach Megan L

    2009-05-01

    Full Text Available Abstract Background Virtual screening is used to distinguish potential leads from inactive compounds in a database of chemical samples. One method for accomplishing this is by docking compounds into the structure of a receptor binding site in order to rank-order compounds by the quality of the interactions they form with the receptor. It is generally established that docking can be reasonably successful at generating good poses of a ligand in an active site. However, the scoring functions that are used with docking are typically not successful at correctly ranking ligands according to binding affinity or even distinguishing correct poses of a given ligand from incorrect ones. Results We have developed a simple method for reducing the number of false positives in a virtual screen, meaning ligands which are scored highly by the docking program but do not bind well in reality. This method uses a docking program for pose generation without regard to scoring, followed by filtering with receptor-based pharmacophore searches. We applied it to three test-case targets: neuraminidase A, cyclin-dependent kinase 2, and the C1 domain of protein kinase C. Conclusion The pharmacophore filtering method can perform better than more traditional docking + scoring methods, and allows the advantages of both docking-based and pharmacophore-based approaches to virtual screening to be fully realized.

  20. Robots arm motion representation in Petri NETS using sequent calculus

    Directory of Open Access Journals (Sweden)

    Syed Uzair Ahmad

    2015-12-01

    Full Text Available There are many sort of motion in robots structure. Such as the robot locomotion robot jumps robots picking and so on but all are presented through Petri NETS. The one motion which is also the important one and most worthy motion of the robots is the robots arm motion. Which till yet not represented through Petri NETS. In this paper we are going to represent the motion of the robot arm in different angles and different aspect, such as up, down, circular, back and front moment of the robot arm, through Petri net we can present the complex form of motions into simplex paths.

  1. Alpha complexes in protein structure prediction

    DEFF Research Database (Denmark)

    Winter, Pawel; Fonseca, Rasmus

    2015-01-01

    Reducing the computational effort and increasing the accuracy of potential energy functions is of utmost importance in modeling biological systems, for instance in protein structure prediction, docking or design. Evaluating interactions between nonbonded atoms is the bottleneck of such computations......-complexes and kinetic a-complexes in protein related problems (e.g., protein structure prediction and protein-ligand docking) deserves furhter investigation.)...

  2. Sequence alignment reveals possible MAPK docking motifs on HIV proteins.

    Directory of Open Access Journals (Sweden)

    Perry Evans

    Full Text Available Over the course of HIV infection, virus replication is facilitated by the phosphorylation of HIV proteins by human ERK1 and ERK2 mitogen-activated protein kinases (MAPKs. MAPKs are known to phosphorylate their substrates by first binding with them at a docking site. Docking site interactions could be viable drug targets because the sequences guiding them are more specific than phosphorylation consensus sites. In this study we use multiple bioinformatics tools to discover candidate MAPK docking site motifs on HIV proteins known to be phosphorylated by MAPKs, and we discuss the possibility of targeting docking sites with drugs. Using sequence alignments of HIV proteins of different subtypes, we show that MAPK docking patterns previously described for human proteins appear on the HIV matrix, Tat, and Vif proteins in a strain dependent manner, but are absent from HIV Rev and appear on all HIV Nef strains. We revise the regular expressions of previously annotated MAPK docking patterns in order to provide a subtype independent motif that annotates all HIV proteins. One revision is based on a documented human variant of one of the substrate docking motifs, and the other reduces the number of required basic amino acids in the standard docking motifs from two to one. The proposed patterns are shown to be consistent with in silico docking between ERK1 and the HIV matrix protein. The motif usage on HIV proteins is sufficiently different from human proteins in amino acid sequence similarity to allow for HIV specific targeting using small-molecule drugs.

  3. Game Theoretic Approach to Post-Docked Satellite Control

    Science.gov (United States)

    Hiramatsu, Takashi; Fitz-Coy, Norman G.

    2007-01-01

    This paper studies the interaction between two satellites after docking. In order to maintain the docked state with uncertainty in the motion of the target vehicle, a game theoretic controller with Stackelberg strategy to minimize the interaction between the satellites is considered. The small perturbation approximation leads to LQ differential game scheme, which is validated to address the docking interactions between a service vehicle and a target vehicle. The open-loop solution are compared with Nash strategy, and it is shown that less control efforts are obtained with Stackelberg strategy.

  4. Linear Actuator System for the NASA Docking System

    Science.gov (United States)

    Dick, Brandon; Oesch, Chris

    2017-01-01

    The Linear Actuator System (LAS) is a major sub-system within the NASA Docking System (NDS). The NDS Block 1 will be used on the Boeing Crew Space Transportation (CST-100) system to achieve docking with the International Space Station. Critical functions in the Soft Capture aspect of docking are performed by the LAS, which implements the Soft Impact Mating and Attenuation Concept (SIMAC). This paper describes the general function of the LAS, the system's key requirements and technical challenges, and the development and qualification approach for the system.

  5. CLUB-MARTINI: Selecting Favourable Interactions amongst Available Candidates, a Coarse-Grained Simulation Approach to Scoring Docking Decoys.

    Directory of Open Access Journals (Sweden)

    Qingzhen Hou

    Full Text Available Large-scale identification of native binding orientations is crucial for understanding the role of protein-protein interactions in their biological context. Measuring binding free energy is the method of choice to estimate binding strength and reveal the relevance of particular conformations in which proteins interact. In a recent study, we successfully applied coarse-grained molecular dynamics simulations to measure binding free energy for two protein complexes with similar accuracy to full-atomistic simulation, but 500-fold less time consuming. Here, we investigate the efficacy of this approach as a scoring method to identify stable binding conformations from thousands of docking decoys produced by protein docking programs. To test our method, we first applied it to calculate binding free energies of all protein conformations in a CAPRI (Critical Assessment of PRedicted Interactions benchmark dataset, which included over 19000 protein docking solutions for 15 benchmark targets. Based on the binding free energies, we ranked all docking solutions to select the near-native binding modes under the assumption that the native-solutions have lowest binding free energies. In our top 100 ranked structures, for the 'easy' targets that have many near-native conformations, we obtain a strong enrichment of acceptable or better quality structures; for the 'hard' targets without near-native decoys, our method is still able to retain structures which have native binding contacts. Moreover, in our top 10 selections, CLUB-MARTINI shows a comparable performance when compared with other state-of-the-art docking scoring functions. As a proof of concept, CLUB-MARTINI performs remarkably well for many targets and is able to pinpoint near-native binding modes in the top selections. To the best of our knowledge, this is the first time interaction free energy calculated from MD simulations have been used to rank docking solutions at a large scale.

  6. Diverse, high-quality test set for the validation of protein-ligand docking performance.

    Science.gov (United States)

    Hartshorn, Michael J; Verdonk, Marcel L; Chessari, Gianni; Brewerton, Suzanne C; Mooij, Wijnand T M; Mortenson, Paul N; Murray, Christopher W

    2007-02-22

    A procedure for analyzing and classifying publicly available crystal structures has been developed. It has been used to identify high-resolution protein-ligand complexes that can be assessed by reconstructing the electron density for the ligand using the deposited structure factors. The complexes have been clustered according to the protein sequences, and clusters have been discarded if they do not represent proteins thought to be of direct interest to the pharmaceutical or agrochemical industry. Rules have been used to exclude complexes containing non-drug-like ligands. One complex from each cluster has been selected where a structure of sufficient quality was available. The final Astex diverse set contains 85 diverse, relevant protein-ligand complexes, which have been prepared in a format suitable for docking and are to be made freely available to the entire research community (http://www.ccdc.cam.ac.uk). The performance of the docking program GOLD against the new set is assessed using a variety of protocols. Relatively unbiased protocols give success rates of approximately 80% for redocking into native structures, but it is possible to get success rates of over 90% with some protocols.

  7. Economic Impacts From Spending by Private Dock Owners at Hartwell Lake

    Science.gov (United States)

    2008-03-01

    cost is variable. The lakes and market segments studied were: • Table Rock Lake, community dock • Rough River Lake, community dock • Pomme de... Terre Lake, community dock • Harry S. Truman Dam and Reservoir, marina • Raystown Lake, marina • Hartwell Lake, private dock • Lake Barkley, private

  8. VinaMPI: facilitating multiple receptor high-throughput virtual docking on high-performance computers.

    Science.gov (United States)

    Ellingson, Sally R; Smith, Jeremy C; Baudry, Jerome

    2013-09-30

    The program VinaMPI has been developed to enable massively large virtual drug screens on leadership-class computing resources, using a large number of cores to decrease the time-to-completion of the screen. VinaMPI is a massively parallel Message Passing Interface (MPI) program based on the multithreaded virtual docking program AutodockVina, and is used to distribute tasks while multithreading is used to speed-up individual docking tasks. VinaMPI uses a distribution scheme in which tasks are evenly distributed to the workers based on the complexity of each task, as defined by the number of rotatable bonds in each chemical compound investigated. VinaMPI efficiently handles multiple proteins in a ligand screen, allowing for high-throughput inverse docking that presents new opportunities for improving the efficiency of the drug discovery pipeline. VinaMPI successfully ran on 84,672 cores with a continual decrease in job completion time with increasing core count. The ratio of the number of tasks in a screening to the number of workers should be at least around 100 in order to have a good load balance and an optimal job completion time. The code is freely available and downloadable. Instructions for downloading and using the code are provided in the Supporting Information.

  9. Influence of protonation, tautomeric, and stereoisomeric states on protein-ligand docking results.

    Science.gov (United States)

    ten Brink, Tim; Exner, Thomas E

    2009-06-01

    In this work, we present a systematical investigation of the influence of ligand protonation states, stereoisomers, and tautomers on results obtained with the two protein-ligand docking programs GOLD and PLANTS. These different states were generated with a fully automated tool, called SPORES (Structure PrOtonation and Recognition System). First, the most probable protonations, as defined by this rule based system, were compared to the ones stored in the well-known, manually revised CCDC/ASTEX data set. Then, to investigate the influence of the ligand protonation state on the docking results, different protonation states were created. Redocking and virtual screening experiments were conducted demonstrating that both docking programs have problems in identifying the correct protomer for each complex. Therefore, a preselection of plausible protomers or the improvement of the scoring functions concerning their ability to rank different molecules/states is needed. Additionally, ligand stereoisomers were tested for a subset of the CCDC/ASTEX set, showing similar problems regarding the ranking of these stereoisomers as the ranking of the protomers.

  10. Spectroscopic and molecular docking studies on the interaction of troxerutin with DNA.

    Science.gov (United States)

    Subastri, A; Ramamurthy, C H; Suyavaran, A; Mareeswaran, R; Lokeswara Rao, P; Harikrishna, M; Suresh Kumar, M; Sujatha, V; Thirunavukkarasu, C

    2015-01-01

    Troxerutin (TXER) is a derivative of naturally occurring bioflavonoid rutin. It possesses different biological activities in rising clinical world. The biological activity possessed by most of the drugs mainly targets on macromolecules. Hence, in the current study we have examined the interaction mechanism of TXER with calf thymus DNA (CT-DNA) by using various spectroscopic methods, isothermal titration calorimetry (ITC) and molecular docking studies. Further, DNA cleavage study was carried out to find the DNA protection activity of TXER. UV-absorption and emission spectroscopy showed low binding constant values via groove binding. Circular dichroism study indicates that TXER does not modify native B-form of DNA, and it retains the native B-conformation. Furthermore, no effective positive potential peak shift was observed in TXER-DNA complex during electrochemical analysis by which it represents an interaction of TXER with DNA through groove binding. Molecular docking study showed thymine guanine based interaction with docking score -7.09 kcal/mol. This result was compared to experimental ITC value. The DNA cleavage study illustrates that TXER does not cause any DNA damage as well as TXER showed DNA protection against hydroxyl radical induced DNA damage. From this study, we conclude that TXER interacts with DNA by fashion of groove binding.

  11. Application of Enhanced Sampling Monte Carlo Methods for High-Resolution Protein-Protein Docking in Rosetta.

    Directory of Open Access Journals (Sweden)

    Zhe Zhang

    Full Text Available The high-resolution refinement of docked protein-protein complexes can provide valuable structural and mechanistic insight into protein complex formation complementing experiment. Monte Carlo (MC based approaches are frequently applied to sample putative interaction geometries of proteins including also possible conformational changes of the binding partners. In order to explore efficiency improvements of the MC sampling, several enhanced sampling techniques, including temperature or Hamiltonian replica exchange and well-tempered ensemble approaches, have been combined with the MC method and were evaluated on 20 protein complexes using unbound partner structures. The well-tempered ensemble method combined with a 2-dimensional temperature and Hamiltonian replica exchange scheme (WTE-H-REMC was identified as the most efficient search strategy. Comparison with prolonged MC searches indicates that the WTE-H-REMC approach requires approximately 5 times fewer MC steps to identify near native docking geometries compared to conventional MC searches.

  12. COMPUTER AIDED DESIGN OF SELECTIVE CALCIUM CHANNEL BLOCKERS: USING PHARMACOPHORE - BASED AND DOCKING SIMULATIONS

    Directory of Open Access Journals (Sweden)

    Reetu

    2012-03-01

    Full Text Available In the present study, 3-D QSAR analysis was performed on the previously synthesized and evaluated derivatives of novel 2-arylthiazolidinones as selective analgesic N-type calcium channel blockers. Calcium Channel blockers is the molecular target responsible for the treatment of neuropathic and inflammatory pain. The 3D-QSAR study based on the principle of the alignment of pharmacophoric features by PHASE module of Schrodinger suite has been carried out on the same set of calcium channel blockers. Statistically significant 3-D QSAR model (R2=0.9288 were generated using 21 molecules in the training set. The predictive ability of model was determined using a randomly chosen test set of 6 molecules which gave predictive correlation coefficients (R2pred of 0.946 for 3-D models, indicating good predictive power. PHASE pharmacophore hypothesis AAHR.13 may correspond very closely to the interactions recorded in the active site of the ligand bound complex. These studies produced models with high correlation coefficient and good predictive abilities. Docking studies were also carried out wherein these analogues were docked into the active sites of COX-2 to analyze the receptor-ligand interactions that confer selectivity for COX-2. Compound 2 have the highest dock score (-7.28. In the active site, there are some strong hydrogen-bonding interactions observed between residues GLU67, ALA103, ASP96, SER184 and ASP22. Additionally a correlation of the quantitative structure –activity relationship data and the docking results is found to validate each other and suggest the importance of the binding step in overall drug action.

  13. Designing coarse grained-and atom based-potentials for protein-protein docking

    Directory of Open Access Journals (Sweden)

    Tobi Dror

    2010-11-01

    Full Text Available Abstract Background Protein-protein docking is a challenging computational problem in functional genomics, particularly when one or both proteins undergo conformational change(s upon binding. The major challenge is to define a scoring function soft enough to tolerate these changes and specific enough to distinguish between near-native and "misdocked" conformations. Results Using a linear programming (LP technique, we developed two types of potentials: (i Side chain-based and (ii Heavy atom-based. To achieve this we considered a set of 161 transient complexes and generated a large set of putative docked structures (decoys, based on a shape complementarity criterion, for each complex. The demand on the potentials was to yield, for the native (correctly docked structure, a potential energy lower than those of any of the non-native (misdocked structures. We show that the heavy atom-based potentials were able to comply with this requirement but not the side chain-based one. Thus, despite the smaller number of parameters, the capability of heavy atom-based potentials to discriminate between native and "misdocked" conformations is improved relative to those of the side chain-based potentials. The performance of the atom-based potentials was evaluated by a jackknife test on a set of 50 complexes taken from the Zdock2.3 decoys set. Conclusions Our results show that, using the LP approach, we were able to train our potentials using a dataset of transient complexes only the newly developed potentials outperform three other known potentials in this test.

  14. Docking and scoring of metallo-beta-lactamases inhibitors

    DEFF Research Database (Denmark)

    Olsen, Lars; Pettersson, Ingrid; Hemmingsen, Lars

    2004-01-01

    The performance of the AutoDock, GOLD and FlexX docking programs was evaluated for docking of dicarboxylic acid inhibitors into metallo-beta-lactamases (MBLs). GOLD provided the best overall performance, with RMSDs between experimental and docked structures of 1.8-2.6 A and a good correlation...... between the experimentally determined MBL-inhibitor affinities and the GOLD scores. GOLD was selected for a test including a broad spectrum of inhibitors for which experimental MBL-inhibitor binding affinities are available. This study revealed that (1) for most compound classes (dicarboxylic acids...... and descriptors associated with binding of the IMP-1 inhibitors to the enzyme. The external Q2 for the test set is 0.73. This final model for prediction of IMP-1 MBL-inhibitor affinity handled all known classes of MBL-inhibitors, except small sulphur compounds....

  15. Virtual Screening with AutoDock: Theory and Practice

    Science.gov (United States)

    Cosconati, Sandro; Forli, Stefano; Perryman, Alex L.; Harris, Rodney; Goodsell, David S.; Olson, Arthur J.

    2011-01-01

    Importance to the field Virtual screening is a computer-based technique for identifying promising compounds to bind to a target molecule of known structure. Given the rapidly increasing number of protein and nucleic acid structures, virtual screening continues to grow as an effective method for the discovery of new inhibitors and drug molecules. Areas covered in this review We describe virtual screening methods that are available in the AutoDock suite of programs, and several of our successes in using AutoDock virtual screening in pharmaceutical lead discovery. What the reader will gain A general overview of the challenges of virtual screening is presented, along with the tools available in the AutoDock suite of programs for addressing these challenges. Take home message Virtual screening is an effective tool for the discovery of compounds for use as leads in drug discovery, and the free, open source program AutoDock is an effective tool for virtual screening. PMID:21532931

  16. Yada: a novel tool for molecular docking calculations

    Science.gov (United States)

    Piotto, S.; Di Biasi, L.; Fino, R.; Parisi, R.; Sessa, L.; Concilio, S.

    2016-09-01

    Molecular docking is a computational method employed to estimate the binding between a small ligand (the drug candidate) and a protein receptor that has become a standard part of workflow in drug discovery. Generally, when the binding site is known and a molecule is similar to known ligands, the most popular docking methods are rather accurate in the prediction of the geometry. Unfortunately, when the binding site is unknown, the blind docking analysis requires large computational resources and the results are often not accurate. Here we present Yada, a new tool for molecular docking that is capable to distribute efficiently calculations onto general purposes computer grid and that combines biological and structural information of the receptor. Yada is available for Windows and Linux and it is free to download at >www.yada.unisa.it.

  17. Optimal Rendezvous and Docking Simulator for Elliptical Orbits Project

    Data.gov (United States)

    National Aeronautics and Space Administration — It is proposed to develop and implement a simulation of spacecraft rendezvous and docking guidance, navigation, and control in elliptical orbit. The foundation of...

  18. Discovery of potential cyclooxygenase inhibitors using in silico docking studies

    Directory of Open Access Journals (Sweden)

    Arumugam Madeswaran

    2012-03-01

    Full Text Available This study deals with the evaluation of the cyclooxygenase inhibitory activity of flavonoids (tangeritin, morin, rhamnetin, theaflavin, pachypodol, eriodictyol, homoeriodictyol, aromadedrin, okanin using in silico docking studies. In silico docking studies were carried out using AutoDock 4.2. Three important parameters like binding energy, inhibition constant and intermolecular energy were determined. The results showed that all the selected flavonoids showed binding energy ranging between -8.77 kcalmol-1 to -6.10 kcalmol-1 when compared with that of the standard (-8.30 kcalmol-1. Intermolecular energy (-10.56 kcalmol-1 to -7.89 kcalmol-1 and inhibition constant (373.91 nM to 34.03 µM of the ligands also coincide with the binding energy. All the selected flavonoids contributed cyclooxygenase inhibitory activity because of its structural parameters. These molecular docking analyses could lead to the further development of potent cyclooxygenase inhibitors.

  19. AggieSat: Autonomous Rendezvous and Docking Technology Demonstrator Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Current autonomous rendezvous and docking (AR&D) capability in low Earth orbit (LEO) is constrained by sensor and effector mass, power, and accuracy limits. To...

  20. 300,000-tonnage Crude Oil Dock Put into Operation

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Aproject of Jointly establishing 300,000-tonnage crude oil dock of Tianjin Port has been put into operations, thanks to its outut grid successfully connected with oil pipeline of Sinopec Tanggu reservior.

  1. Robotic Arm Biobarrier Cable

    Science.gov (United States)

    2008-01-01

    This image, taken by the Surface Stereo Imager on NASA's Phoenix Mars Lander on the 14th Martian day of the mission (June 7, 2008), shows the cable that held the Robotic Arm's biobarrier in place during flight has snapped. The cable's springs retracted to release the biobarrier right after landing. To the lower right of the image a spring is visible. Extending from that spring is a length of cable that snapped during the biobarrier's release. A second spring separated from the cable when it snapped and has been photographed on the ground under the lander near one of the legs. The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  2. The Neanderthal lower arm.

    Science.gov (United States)

    De Groote, Isabelle

    2011-10-01

    Neanderthal forearms have been described as being very powerful. Different individual features in the lower arm bones have been described to distinguish Neanderthals from modern humans. In this study, the overall morphology of the radius and ulna is considered, and morphological differences among Neanderthals, Upper Paleolithic Homo sapiens and recent H. sapiens are described. Comparisons among populations were made using a combination of 3D geometric morphometrics and standard multivariate methods. Comparative material included all available complete radii and ulnae from Neanderthals, early H. sapiens and archaeological and recent human populations, representing a wide geographical and lifestyle range. There are few differences among the populations when features are considered individually. Neanderthals and early H. sapiens fell within the range of modern human variation. When the suite of measurements and shapes were analyzed, differences and similarities became apparent. The Neanderthal radius is more laterally curved, has a more medially placed radial tuberosity, a longer radial neck, a more antero-posteriorly ovoid head and a well-developed proximal interosseous crest. The Neanderthal ulna has a more anterior facing trochlear notch, a lower M. brachialis insertion, larger relative mid-shaft size and a more medio-lateral and antero-posterior sinusoidal shaft. The Neanderthal lower arm morphology reflects a strong cold-adapted short forearm. The forearms of H. sapiens are less powerful in pronation and supination. Many differences between Neanderthals and H. sapiens can be explained as a secondary consequence of the hyper-polar body proportions of the Neanderthals, but also as retentions of the primitive condition of other hominoids.

  3. Companies hone in on radar-docking technology

    Science.gov (United States)

    Howell, Elizabeth

    2009-11-01

    As NASA prepares to retire the Space Shuttle next year, two private space firms have tested docking technology that could be used on the next generation of US spacecraft. In September, Canadian firm Neptec tested a new radar system on the Space Shuttle Discovery that allows spacecraft to dock more easily. Meanwhile, Space Exploration Technologies (SpaceX) based in California has revealed that it tested out a new proximity sensor, dubbed "Dragoneye", on an earlier shuttle mission in July.

  4. Scheduling inbound and outbound trucks at cross docking terminals

    OpenAIRE

    Nils Boysen; Malte Fliedner; Armin Scholl

    2007-01-01

    At cross docking terminals, shipments from inbound trucks are unloaded, sorted and moved to dispatch points where they are directly loaded onto outbound trucks for an immediate delivery elsewhere in the distribution system. This warehouse management concept aims at realizing economies in transportation cost by consolidating divergent shipments to full truckloads without requiring excessive inventory at the cross dock. The efficient operation of such a system requires an appropriate coordinati...

  5. Identification of hot-spot residues in protein-protein interactions by computational docking

    Directory of Open Access Journals (Sweden)

    Fernández-Recio Juan

    2008-10-01

    Full Text Available Abstract Background The study of protein-protein interactions is becoming increasingly important for biotechnological and therapeutic reasons. We can define two major areas therein: the structural prediction of protein-protein binding mode, and the identification of the relevant residues for the interaction (so called 'hot-spots'. These hot-spot residues have high interest since they are considered one of the possible ways of disrupting a protein-protein interaction. Unfortunately, large-scale experimental measurement of residue contribution to the binding energy, based on alanine-scanning experiments, is costly and thus data is fairly limited. Recent computational approaches for hot-spot prediction have been reported, but they usually require the structure of the complex. Results We have applied here normalized interface propensity (NIP values derived from rigid-body docking with electrostatics and desolvation scoring for the prediction of interaction hot-spots. This parameter identifies hot-spot residues on interacting proteins with predictive rates that are comparable to other existing methods (up to 80% positive predictive value, and the advantage of not requiring any prior structural knowledge of the complex. Conclusion The NIP values derived from rigid-body docking can reliably identify a number of hot-spot residues whose contribution to the interaction arises from electrostatics and desolvation effects. Our method can propose residues to guide experiments in complexes of biological or therapeutic interest, even in cases with no available 3D structure of the complex.

  6. Effects of administration of a local anaesthetic and/or an NSAID and of docking length on the behaviour of piglets during 5 h after tail docking

    DEFF Research Database (Denmark)

    Herskin, Mette S.; Di Giminiani, Pierpaolo; Thodberg, Karen

    2016-01-01

    In many countries, piglets are tail docked to prevent tail biting. The aim of this study was 1) to evaluate the efficacy of a local anaesthetic and/or NSAID to reduce pain caused by tail docking; and 2) to examine interactions with docking length. This was examined in 295 piglets docked by hot iron...... cautery 2–4 days after birth and based on behaviour during docking as well as the following 5 h. The study involved three main factors: local anaesthetic (Lidocain), NSAID (Meloxicam) and docking length. Either 100%, 75%, 50% or 25% of the tails were left on the body of the piglets. Irrespective...... of the tail length, tail docking led to signs of procedural pain, which could be reduced by administration of Lidocain. Preemptive use of Meloxicam did not affect the signs of procedural pain. The results show that tail docking led to behavioural changes throughout the 5 h observation period indicating...

  7. Arm coordination in octopus crawling involves unique motor control strategies.

    Science.gov (United States)

    Levy, Guy; Flash, Tamar; Hochner, Binyamin

    2015-05-04

    To cope with the exceptional computational complexity that is involved in the control of its hyper-redundant arms [1], the octopus has adopted unique motor control strategies in which the central brain activates rather autonomous motor programs in the elaborated peripheral nervous system of the arms [2, 3]. How octopuses coordinate their eight long and flexible arms in locomotion is still unknown. Here, we present the first detailed kinematic analysis of octopus arm coordination in crawling. The results are surprising in several respects: (1) despite its bilaterally symmetrical body, the octopus can crawl in any direction relative to its body orientation; (2) body and crawling orientation are monotonically and independently controlled; and (3) contrasting known animal locomotion, octopus crawling lacks any apparent rhythmical patterns in limb coordination, suggesting a unique non-rhythmical output of the octopus central controller. We show that this uncommon maneuverability is derived from the radial symmetry of the arms around the body and the simple pushing-by-elongation mechanism by which the arms create the crawling thrust. These two together enable a mechanism whereby the central controller chooses in a moment-to-moment fashion which arms to recruit for pushing the body in an instantaneous direction. Our findings suggest that the soft molluscan body has affected in an embodied way [4, 5] the emergence of the adaptive motor behavior of the octopus.

  8. Homology modeling and docking studies of IscS from extremophile Acidithiobacillus ferrooxidans

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The gene iscS-3 from Acidithiobacillus ferrooxidans may play a central role in the delivery of sulfur to a variety of metabolic pathways in this organism. For insight into the sulfur metabolic mechanism of the bacteria, an integral three-dimensional (3D) molecular structure of the protein encoded by this gene was built by homology modeling techniques, refined by molecular dynamics simulations, assessed by PROFILE-3D and PROSTAT programs and further used to search bind sites, carry out flexible docking with cofactor pyridoxal 5'-phosphate(PLP) and substrate cysteine and hereby detect its key residues. Through these procedures, the detail conformations of PLP-IscS(P-I) and cysteine-PLP-IscS(C-P-I) complexes were obtained. In P-I complex, the residues of Lys208, His106, Thr78, Ser205, His207, Asp182 and Gln185 have large interaction energies and/or hydrogen bonds fixation with PLP. In C-P-I complex, the amino group in cysteine is very near His106, Lys208 and PLP, the interaction energies for cysteine with them are very high. The above results are well consistent with those experimental facts of the homologues from other sources. Interestingly, the four residues of Glu105, Glu79, Ser203 and His180 in P-I docking and the residue of Lys213 in C-P-I docking also have great interaction energies, which are fitly conservation in IscSs from all kinds of sources but have not been identified before. From these results, this gene can be confirmed at 3D level to encode the iron-sulfur cluster assembly protein lscS and subsequently play a sulfur traffic role. Furthermore, the substrate cysteine can be presumed to be effectively recruited into the active site. Finally, the above detected key residues can be conjectured to be directly responsible for the bind and/or catalysis of PLP and cysteine.

  9. Arménie

    Directory of Open Access Journals (Sweden)

    François Verdier

    2012-04-01

    Full Text Available L’Arménie est une petite république du Caucase, à la limite sud–est de l’Europe, qui a gagné son autonomie en 1990 après l’ouverture du bloc soviétique. Le nouveau Ministère du Patrimoine a sollicité la coopération de la France pour mettre en place une nouvelle politique culturelle. Tout d’abord, une évaluation sur place de la situation dans les domaines des monuments historiques, de l’archéologie et de l’Inventaire a permis d’envisager les réponses à proposer. Pour la demande d’informatisation des dossiers d’inventaire déjà réalisés sous l’autorité de l’Académie de Saint–Petersbourg, nous avons proposé de former des chercheurs arméniens aux méthodes et techniques de l’Inventaire général. L’accueil d’une stagiaire pendant trois mois au service régional de l’Inventaire de Haute–Normandie a été suivi par la mise en place d’un équipement informatique à Yérévan, puis par l’accueil et la formation de techniciens informaticiens et photographes arméniens. De retour dans leur pays ils ont commencé à remettre en place un service d’inventaire dont le programme comprend la création d’une base de données patrimoniales, le recensement de la ville de Yérévan, la numérisation d’images pour la publication d’un indicateur du patrimoine et la préparation de dossiers de protection au titre du patrimoine mondial.The Armenian heritage comprises both archaeological remains of towns destroyed by never–ending wars and a number of old churches from the eleventh and twelfth centuries. Yerevan, the capital of Armenia, was founded three thousand years ago and is one of Europe’s oldest capitals. From 1925 it has developed according to an ambitious urban planning project. After the major political upheavals of 1991, a special ministry was created to look after the architectural and movable heritage of the country and to promote the Armenian national identity. A mission in Yerevan was

  10. How different from random are docking predictions when ranked by scoring functions?

    DEFF Research Database (Denmark)

    Feliu, Elisenda; Oliva, Baldomero

    2010-01-01

    Docking algorithms predict the structure of protein-protein interactions. They sample the orientation of two unbound proteins to produce various predictions about their interactions, followed by a scoring step to rank the predictions. We present a statistical assessment of scoring functions used...... to rank near-native orientations, applying our statistical analysis to a benchmark dataset of decoys of protein-protein complexes and assessing the statistical significance of the outcome in the Critical Assessment of PRedicted Interactions (CAPRI) scoring experiment. A P value was assigned that depended...

  11. ARM Soc Based Enotebook

    Directory of Open Access Journals (Sweden)

    Pranita C Bawankar

    2014-05-01

    Full Text Available In recent years, electronic media has grown very fast replacing papers, tape devices, books, etc. The new technologies provide large number of data into single device, fast searching options and more readability than ever. As eBooks are replacing books; we are proposing ENotebook system in which user can write as he did in notebook, save, searches and then reread content. This paper presents design and development of ENotebook using ARM7. The system uses touch screen to get input data and operations like save, delete, open & close of data file. All data sensed by touch screen is digitized by internal ADCs of LPC2148 microcontroller which gives low power platform with fast execution. The output is shown on graphical LCD. Whatever user writes on screen it may need to save for future use. The content of such hand written data will be in graphical/pictorial form hence required large of memory for storage. We can provide external memory using pen drive, memory card, EEPROM etc. in this system we are using SD card interfacing through SPI port.

  12. ARCADE small-scale docking mechanism for micro-satellites

    Science.gov (United States)

    Boesso, A.; Francesconi, A.

    2013-05-01

    The development of on-orbit autonomous rendezvous and docking (ARD) capabilities represents a key point for a number of appealing mission scenarios that include activities of on-orbit servicing, automated assembly of modular structures and active debris removal. As of today, especially in the field of micro-satellites ARD, many fundamental technologies are still missing or require further developments and micro-gravity testing. In this framework, the University of Padova, Centre of Studies and Activities for Space (CISAS), developed the Autonomous Rendezvous Control and Docking Experiment (ARCADE), a technology demonstrator intended to fly aboard a BEXUS stratospheric balloon. The goal was to design, build and test, in critical environment conditions, a proximity relative navigation system, a custom-made reaction wheel and a small-size docking mechanism. The ARCADE docking mechanism was designed against a comprehensive set of requirements and it can be classified as small-scale, central, gender mating and unpressurized. The large use of commercial components makes it low-cost and simple to be manufactured. Last, it features a good tolerance to off-nominal docking conditions and a by-design soft docking capability. The final design was extensively verified to be compliant with its requirements by means of numerical simulations and physical testing. In detail, the dynamic behaviour of the mechanism in both nominal and off-nominal conditions was assessed with the multibody dynamics analysis software MD ADAMS 2010 and functional tests were carried out within the fully integrated ARCADE experiment to ensure the docking system efficacy and to highlight possible issues. The most relevant results of the study will be presented and discussed in conclusion to this paper.

  13. Trends in the Binding of Cell Penetrating Peptides to siRNA: A Molecular Docking Study

    Science.gov (United States)

    Gunathunge, B. G. C. M.; Wimalasiri, P. N.; Karunaratne, D. N.

    2017-01-01

    The use of gene therapeutics, including short interfering RNA (siRNA), is limited by the lack of efficient delivery systems. An appealing approach to deliver gene therapeutics involves noncovalent complexation with cell penetrating peptides (CPPs) which are able to penetrate the cell membranes of mammals. Although a number of CPPs have been discovered, our understanding of their complexation and translocation of siRNA is as yet insufficient. Here, we report on computational studies comparing the binding affinities of CPPs with siRNA, considering a variety of CPPs. Specifically, seventeen CPPs from three different categories, cationic, amphipathic, and hydrophobic CPPs, were studied. Molecular mechanics were used to minimize structures, while molecular docking calculations were used to predict the orientation and favorability of sequentially binding multiple peptides to siRNA. Binding scores from docking calculations were highest for amphipathic peptides over cationic and hydrophobic peptides. Results indicate that initial complexation of peptides will likely occur along the major groove of the siRNA, driven by electrostatic interactions. Subsequent binding of CPPs is likely to occur in the minor groove and later on bind randomly, to siRNA or previously bound CPPs, through hydrophobic interactions. However, hydrophobic CPPs do not show this binding pattern. Ultimately binding yields a positively charged nanoparticle capable of noninvasive cellular import of therapeutic molecules.

  14. DNA topoisomerase-directed anticancerous alkaloids: ADMET-based screening, molecular docking, and dynamics simulation.

    Science.gov (United States)

    Singh, Swati; Das, Tamal; Awasthi, Manika; Pandey, Veda P; Pandey, Brijesh; Dwivedi, Upendra N

    2016-01-01

    Topoisomerases (Topo I and II) have been looked as crucial targets against various types of cancers. In the present paper, 100 anticancerous alkaloids were subjected to in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) analyses to investigate their pharmacokinetic properties. Out of 100 alkaloids, only 18 were found to fulfill all the ADMET descriptors and obeyed the Lipinski's rule of five. All the 18 alkaloids were found to dock successfully within the active site of both Topo I and II. A comparison of the inhibitory potential of 18 screened alkaloids with those of selected drugs revealed that four alkaloids (oliveroline, coptisine, aristolactam, and piperine) inhibited Topo I, whereas six alkaloids (oliveroline, aristolactam, anonaine, piperine, coptisine, and liriodenine) inhibited Topo II more strongly than those of their corresponding drugs, topotecan and etoposide, respectively, with oliveroline being the outstanding. The stability of the complexes of Topo I and II with the best docked alkaloid, oliveroline, was further analyzed using 10 nSec molecular dynamics simulation and compared with those of the respective drugs, namely, topotecan and etoposide, which revealed stabilization of these complexes within 5 nSec of simulation with better stability of Topo II complex than that of Topo I.

  15. Empirical scoring functions for advanced protein-ligand docking with PLANTS.

    Science.gov (United States)

    Korb, Oliver; Stützle, Thomas; Exner, Thomas E

    2009-01-01

    In this paper we present two empirical scoring functions, PLANTS(CHEMPLP) and PLANTS(PLP), designed for our docking algorithm PLANTS (Protein-Ligand ANT System), which is based on ant colony optimization (ACO). They are related, regarding their functional form, to parts of already published scoring functions and force fields. The parametrization procedure described here was able to identify several parameter settings showing an excellent performance for the task of pose prediction on two test sets comprising 298 complexes in total. Up to 87% of the complexes of the Astex diverse set and 77% of the CCDC/Astex clean listnc (noncovalently bound complexes of the clean list) could be reproduced with root-mean-square deviations of less than 2 A with respect to the experimentally determined structures. A comparison with the state-of-the-art docking tool GOLD clearly shows that this is, especially for the druglike Astex diverse set, an improvement in pose prediction performance. Additionally, optimized parameter settings for the search algorithm were identified, which can be used to balance pose prediction reliability and search speed.

  16. Interaction of prodigiosin with HSA and β-Lg: Spectroscopic and molecular docking studies.

    Science.gov (United States)

    Rastegari, Banafsheh; Karbalaei-Heidari, Hamid Reza; Yousefi, Reza; Zeinali, Sedigheh; Nabavizadeh, Masoud

    2016-04-01

    Human serum albumin (HSA) and bovine β-lactoglobulin (β-Lg) are both introduced as blood and oral carrier scaffolds with high affinity for a wide range of pharmaceutical compounds. Prodigiosin, a natural three pyrrolic compound produced by Serratia marcescens, exhibits many pharmaceutical properties associated with health benefits. In the present study, the interaction of prodigiosin with HSA and β-Lg was investigated using fluorescence spectroscopy, circular dichroism (CD) and computational docking. Prodigiosin interacts with the Sudlow's site I of HSA and the calyx of β-Lg with association constant of 4.41 × 10(4) and 1.99 × 10(4) M(-1) to form 1:1 and 2:3 complexes at 300K, respectively. The results indicated that binding of prodigiosin to HSA and β-Lg caused strong fluorescence quenching of both proteins through static quenching mechanism. Electrostatic and hydrophobic interactions are the major forces in the stability of PG-HSA complex with enthalpy- and entropy-driving mode, although the formation of prodigiosin-β-Lg complex is entropy-driven hydrophobic associations. CD spectra showed slight conformational changes in both proteins due to the binding of prodigiosin. Moreover, the ligand displacement assay, pH-dependent interaction and protein-ligand docking study confirmed that the prodigiosin binds to residues located in the subdomain IIA and IIIA of HSA and central calyx of β-Lg.

  17. ARM Lead Mentor Selection Process

    Energy Technology Data Exchange (ETDEWEB)

    Sisterson, DL

    2013-03-13

    The ARM Climate Research Facility currently operates more than 300 instrument systems that provide ground-based observations of the atmospheric column. To keep ARM at the forefront of climate observations, the ARM infrastructure depends heavily on instrument scientists and engineers, also known as Instrument Mentors. Instrument Mentors must have an excellent understanding of in situ and remote-sensing instrumentation theory and operation and have comprehensive knowledge of critical scale-dependent atmospheric processes. They also possess the technical and analytical skills to develop new data retrievals that provide innovative approaches for creating research-quality data sets.

  18. Taxation, stateness and armed groups

    DEFF Research Database (Denmark)

    Hoffmann, Kasper; Vlassenroot, Koen; Marchais, Gauthier

    2016-01-01

    rackets, to the material reciprocation of the recognition of rights. Focusing on the taxation practices of armed groups, the article argues that taxation is at the core of armed groups’ production of public authority and citizenship, and that their modes of taxation are based on long-standing registers...... of authority and practices of rule that originate in the colonial era. In particular, the article shows that by appealing to both local customary and national forms of political community and citizenship, armed groups are able to assume public authority to tax civilians. However, their public authority may...

  19. Telerobotics with whole arm collision avoidance

    Energy Technology Data Exchange (ETDEWEB)

    Wilhelmsen, K.; Strenn, S.

    1993-09-01

    The complexity of teleorbotic operations in a cluttered environment is exacerbated by the need to present collision information to the operator in an understandable fashion. In addition to preventing movements which will cause collisions, a system providing some form of virtual force reflection (VFR) is desirable. With this goal in mind, Lawrence Livermore National Laboratory (LLNL) has installed a kinematically master/slave system and developed a whole arm collision avoidance system which interacts directly with the telerobotic controller. LLNL has also provided a structure to allow for automated upgrades of workcell models and provide collision avoidance even in a dynamically changing workcell.

  20. Complex Regional Pain Syndrome

    Science.gov (United States)

    Complex regional pain syndrome (CRPS) is a chronic pain condition. It causes intense pain, usually in the arms, hands, legs, or feet. ... in skin temperature, color, or texture Intense burning pain Extreme skin sensitivity Swelling and stiffness in affected ...

  1. Machine Vision for Relative Spacecraft Navigation During Approach to Docking

    Science.gov (United States)

    Chien, Chiun-Hong; Baker, Kenneth

    2011-01-01

    This paper describes a machine vision system for relative spacecraft navigation during the terminal phase of approach to docking that: 1) matches high contrast image features of the target vehicle, as seen by a camera that is bore-sighted to the docking adapter on the chase vehicle, to the corresponding features in a 3d model of the docking adapter on the target vehicle and 2) is robust to on-orbit lighting. An implementation is provided for the case of the Space Shuttle Orbiter docking to the International Space Station (ISS) with quantitative test results using a full scale, medium fidelity mock-up of the ISS docking adapter mounted on a 6-DOF motion platform at the NASA Marshall Spaceflight Center Flight Robotics Laboratory and qualitative test results using recorded video from the Orbiter Docking System Camera (ODSC) during multiple orbiter to ISS docking missions. The Natural Feature Image Registration (NFIR) system consists of two modules: 1) Tracking which tracks the target object from image to image and estimates the position and orientation (pose) of the docking camera relative to the target object and 2) Acquisition which recognizes the target object if it is in the docking camera Field-of-View and provides an approximate pose that is used to initialize tracking. Detected image edges are matched to the 3d model edges whose predicted location, based on the pose estimate and its first time derivative from the previous frame, is closest to the detected edge1 . Mismatches are eliminated using a rigid motion constraint. The remaining 2d image to 3d model matches are used to make a least squares estimate of the change in relative pose from the previous image to the current image. The changes in position and in attitude are used as data for two Kalman filters whose outputs are smoothed estimate of position and velocity plus attitude and attitude rate that are then used to predict the location of the 3d model features in the next image.

  2. Characterization of interaction between isoliquiritigenin and bovine serum albumin: Spectroscopic and molecular docking methods

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Jie-hua, E-mail: shijh@zjut.edu.cn [College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310032 (China); State Key Laboratory Breeding Base of Green Chemistry Synthesis Technology, Zhejiang University of Technology, Hangzhou 310032 (China); Wang, Jing; Zhu, Ying-yao; Chen, Jun [College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310032 (China)

    2014-01-15

    The intermolecular interaction between isoliquiritigenin (ISL) and bovine serum albumin (BSA) under imitated physiological conditions was investigated using fluorescence, circular dichromism (CD) and molecular docking methods. The results revealed that the fluorescence quenching of BSA at 338 nm by ISL resulted from the formation of ISL–BSA complex. The number of binding sites (n) for ISL binding on BSA was approximately equal to 1. The experimental and molecular docking results revealed that after binding ISL to BSA, ISL was close to Tyr residue than Trp residue, the binding of ISL to BSA induced a slight change in conformation of BSA but the BSA still retains its secondary structure, the binding process of ISL with BSA is spontaneous, and ISL could be inserted into the hydrophobic cavity of BSA (Site I) in the binding process of ISL with BSA. The enthalpic change (ΔH{sup 0}) and entropic change (ΔS{sup 0}) in the process of interaction of BSA with ISL were –116.74 kJ mol{sup –1} and –286.32 J mol{sup –1} K{sup –1}, respectively, indicating that the main interaction forces of ISL with BSA were Van der Waals and hydrogen bonding interactions. And, it can be suggested from the molecular docking results that the flexibility of ISL plays an important role in increasing the stability of the whole system upon association of ISL with BSA. -- Highlights: • ISL binds to hydrophobic cavity (site I) in BSA and forms 1:1 complex with it. • The fluorescence quenching of BSA induced by ISL is static quenching. • ISL binding results in a decreased α-helix. • The main interaction forces were Van der Waals and hydrogen bonding interactions. • The flexibility of ISL plays an important role in increasing the ISL–BSA stability.

  3. Molecular Docking of 3-Methylindole-containing Drugs Binding into CYP3A4

    Institute of Scientific and Technical Information of China (English)

    MENG Xuan-yu; LI Zhuo; NIU Rui-juan; ZHANG Hong-xing; ZHENG Qing-chuan

    2012-01-01

    Drugs SPD-304(6,7-dimethyl-3- { [methyl-(2-{methyl-[ 1-(3-trifluoromethyl-phenyl)- 1H-indol-3-ylmethyl]-amino}-ethyl)-amino]-methyl}-chromen-4-one) and zafirlukast contain a common structural element of 3-substituted indole moiety which closely relates to a dehydrogenated reaction catalyzed by cytochrome P450s(CYPs).It was reported that the dehydrogenation can produce a reactive electrophilic intermediate which cause toxicities and inactivate CYPs. Drug L-745,870(3-{[4-(4-chlorophenyl)piperazin-l-yl]-methyl}-1H-pyrrolo-2,3-β-pyridine) might have similar effect since it contains the same structural element.We used molecular docking approach combined with molecular dynamics(MD) simulation to model three-dimensional(3D) complex structures of SPD-304,zafirlukast and L-745,870 into CYP3A4,respectively.The results show that these three drugs can stably bind into the active site and the 3-methylene carbons of the drugs keep a reasonable reactive distance from the heme iron.The complex structure of SPD-304-CYP3A4 is in agreement with experimental data.For zafirlukast,the calculation results indicate that 3-methylene carbon might be the dehydrogenation reaction site.Docking model of L-745,870-CYP3A4 shows a potential possibility of L-745,870 dehydrogenated by CYP3A4 at 3-methylene carbon which is in agreement with experiment in vivo.In addition,residues in the phenylalanine cluster as well as S119 and R212 play a critical role in the ligands binding based on our calculations.The docking models could provide some clues to understand the metabolic mechanism of the drugs by CYP3A4.

  4. Seismic vulnerability assessment of an Italian historical masonry dry dock

    Directory of Open Access Journals (Sweden)

    Marco Zucca

    2017-01-01

    Full Text Available The paper presents the seismic vulnerability analysis of the military dry dock built in 1861 inside the Messina’s harbor. The study appears very important not only for the relevance of the dry dock itself, but also for its social, military and symbolic role. As a first step, the historical documentation about the dry dock delivered by the Military Technical Office, in charge of its maintenance, was thoroughly examined. This activity was fundamental to understand the construction methods, the rehabilitation works executed after the severe earthquake of 1908 and, finally, the works carried out to increase the size of the dry dock in 1950. After this first step, numerical seismic analyses were done with some implemented finite element models (FEM of the structure. In each FEM, the vertical loads were applied according to the “construction stages” analysis technique, in order to achieve an appropriate representation of the soil stresses around the structure. The analysis results were evaluated according to the Italian design code (NTC 2008 in order to determine the seismic vulnerability of the dry dock.

  5. GOMoDo: A GPCRs online modeling and docking webserver.

    Directory of Open Access Journals (Sweden)

    Massimo Sandal

    Full Text Available G-protein coupled receptors (GPCRs are a superfamily of cell signaling membrane proteins that include >750 members in the human genome alone. They are the largest family of drug targets. The vast diversity and relevance of GPCRs contrasts with the paucity of structures available: only 21 unique GPCR structures have been experimentally determined as of the beginning of 2013. User-friendly modeling and small molecule docking tools are thus in great demand. While both GPCR structural predictions and docking servers exist separately, with GOMoDo (GPCR Online Modeling and Docking, we provide a web server to seamlessly model GPCR structures and dock ligands to the models in a single consistent pipeline. GOMoDo can automatically perform template choice, homology modeling and either blind or information-driven docking by combining together proven, state of the art bioinformatic tools. The web server gives the user the possibility of guiding the whole procedure. The GOMoDo server is freely accessible at http://molsim.sci.univr.it/gomodo.

  6. Molecular docking assessment of pyridone derivatives as glucokinase activators

    Directory of Open Access Journals (Sweden)

    Y. Nanda Kumar

    2012-10-01

    Full Text Available Background: Mutations in glucokinase (GK gene results in maturity onset diabetes of the young 2 (MODY2. It has been observed that GK activators (GKAs can activate GK structure and promote glucose phosphorylation and bring blood glucose levels to normal condition. The present study is aimed to identify the binding mode of pyridone derivatives (PDs as GKAs through molecular docking study. Methods: GK structure was retrieved from the Protein Data Bank (PDB, protonated and energy minimized. A database was constructed with 29 PDs and docked into the allosteric site specified with Y61, R63, S69 and Y215 residues using Molecular Operating Environment (MOE software. Docking conformations were generated using triangle match algorithm and ranked by London dG scoring function. The binding orientations and strength of interactions were evaluated by ligand interaction module of MOE. Results: Molecular docking of 29 PDs in allosteric site of GK gave reliable docking scores, interestingly arene cationic interactions were observed with the compounds PD1, PD12, PD20 and PD21. R63 residue of allosteric site played a predominant role in binding with PDs. Conclusions: PDs can be potentially useful agents in future management strategies of type 2 diabetes mellitus.

  7. How well do the substrates KISS the enzyme? Molecular docking program selection for feruloyl esterases

    DEFF Research Database (Denmark)

    Udatha, D. B. R. K. Gupta; Sugaya, Nobuyoshi; Olsson, Lisbeth;

    2012-01-01

    Molecular docking is the most commonly used technique in the modern drug discovery process where computational approaches involving docking algorithms are used to dock small molecules into macromolecular target structures. Over the recent years several evaluation studies have been reported...... by independent scientists comparing the performance of the docking programs by using default 'black box' protocols supplied by the software companies. Such studies have to be considered carefully as the docking programs can be tweaked towards optimum performance by selecting the parameters suitable...... Score System' (KISS), a more biochemically meaningful measure for evaluation of docking programs based on pose prediction accuracy....

  8. Bistable Head Positioning Arm Latch

    Science.gov (United States)

    Wasson, Ken; Endo, Juro; Mita, Masahiro; Abelein, Nathan

    A simple, low cost, yet effective device has been developed for immobilizing the head-arm assembly in a disk drive or similar mechanism during power-off conditions. The latching scheme also provides a consistent means of releasing the head-arm assembly from the immobilized position upon power up of the disk drive. The latch uses no electrical power in either immobilized or released state. This design is immune to extreme torque and linear shock forces applied to the disk drive case. The latch system can use the energy stored in the spinning disks to drive the head-arm assembly toward a safe position while simultaneously arming the latch mechanism to secure the head-arm assembly in the safe position upon arrival. A low energy five msec pulse of current drives the latch from one state to the other. Solenoids as presently used in latch mechanisms are bulky, expensive, have variable force characteristics, and often generate contaminants. The latch described in this paper is expected to replace such solenoids. It may also replace small magnet latches, which have limited latch force and apply unwanted torque to a proximate head positioning arm.

  9. Unequal-Arms Michelson Interferometers

    Science.gov (United States)

    Tinto, Massimo; Armstrong, J. W.

    2000-01-01

    Michelson interferometers allow phase measurements many orders of magnitude below the phase stability of the laser light injected into their two almost equal-length arms. If, however, the two arms are unequal, the laser fluctuations can not be removed by simply recombining the two beams. This is because the laser jitters experience different time delays in the two arms, and therefore can not cancel at the photo detector. We present here a method for achieving exact laser noise cancellation, even in an unequal-arm interferometer. The method presented in this paper requires a separate readout of the relative phase in each arm, made by interfering the returning beam in each arm with a fraction of the outgoing beam. By linearly combining the two data sets with themselves, after they have been properly time shifted, we show that it is possible to construct a new data set that is free of laser fluctuations. An application of this technique to future planned space-based laser interferometer detector3 of gravitational radiation is discussed.

  10. Integrating docking and molecular dynamics approaches for a series of proline-based 2,5-diketopiperazines as novel αβ-tubulin inhibitors.

    Science.gov (United States)

    Fani, Najmeh; Bordbar, Abdol-Khalegh; Ghayeb, Yousef; Sepehri, Saghi

    2015-01-01

    In this work, docking tools were utilized in order to study the binding properties of more than five hundred of proline-based 2,5-diketopiperazine in the binding site of αβ-tubulin. Results revealed that 20 compounds among them showed lower binding energies in comparison with Tryprostatin-A, a well known tubulin inhibitor and therefore could be potential inhibitors of tubulin. However, the precise evaluation of binding poses represents the similar binding modes for all of these compounds and Tryprostatin-A. Finally, the best docked complex was subjected to a 25 ns molecular dynamics simulation to further validate the proposed binding mode of this compound.

  11. Structural and molecular docking studies of biologically active mercaptopyrimidine Schiff bases

    Science.gov (United States)

    Kirubavathy, S. Jone; Velmurugan, R.; Karvembu, R.; Bhuvanesh, N. S. P.; Enoch, Israel V. M. V.; Selvakumar, P. Mosae; Premnath, D.; Chitra, S.

    2017-01-01

    Novel Schiff bases derived from the treatment of mercapto-diamino pyrimidine with two different aldehydes are characterized using elemental analysis, single crystal X-ray diffraction and 1H NMR spectroscopy. The pharmacological action of the synthesized compounds viz., antimicrobial, anticancer and antitubercular activities is studied. The Schiff bases show a very good activity against various test pathogens. DNA and β-CD binding interactions of the compounds are studied using UV-Visible absorption and fluorescence spectral measurements. The binding constants of the compounds towards β-CD are in the order of 103 to 104. Molecular docking is done using MOE program on the 3D structure of the enzymes, viz., human thymidylate synthase complexed with dump and raltitrex, candida albicans N-myristoyltransferasepeptidic inhibitor, catalytic domain of protein kinase pKnb from mycobacterium tuberculosis in complex with mitoxantrone, pare, topoisomerase atpase inhibitor, E. coli and lactobacillus casdihydrofolatereductase. The MIC/IC50 values of the Schiff bases are compared with the glide scores from the molecular docking studies. The number of hydrogen bonding interactions between the Schiff bases and amino acid residues are also reported.

  12. Binding interaction between sorafenib and calf thymus DNA: Spectroscopic methodology, viscosity measurement and molecular docking

    Science.gov (United States)

    Shi, Jie-Hua; Chen, Jun; Wang, Jing; Zhu, Ying-Yao

    2015-02-01

    The binding interaction of sorafenib with calf thymus DNA (ct-DNA) was studied using UV-vis absorption spectroscopy, fluorescence emission spectroscopy, circular dichroism (CD), viscosity measurement and molecular docking methods. The experimental results revealed that there was obvious binding interaction between sorafenib and ct-DNA. The binding constant (Kb) of sorafenib with ct-DNA was 5.6 × 103 M-1 at 298 K. The enthalpy and entropy changes (ΔH0 and ΔS0) in the binding process of sorafenib with ct-DNA were -27.66 KJ mol-1 and -21.02 J mol-1 K-1, respectively, indicating that the main binding interaction forces were van der Waals force and hydrogen bonding. The docking results suggested that sorafenib preferred to bind on the minor groove of A-T rich DNA and the binding site of sorafenib was 4 base pairs long. The conformation change of sorafenib in the sorafenib-DNA complex was obviously observed and the change was close relation with the structure of DNA, implying that the flexibility of sorafenib molecule played an important role in the formation of the stable sorafenib-ct-DNA complex.

  13. A spectroscopic and molecular docking approach on the binding of tinzaparin sodium with human serum albumin

    Science.gov (United States)

    Abdullah, Saleh M. S.; Fatma, Sana; Rabbani, Gulam; Ashraf, Jalaluddin M.

    2017-01-01

    Protein bound toxins are poorly removed by conventional extracorporeal therapies. Venous thromboembolism (VTE) is a major cause of morbidity and mortality in patients with cancer. The interaction between tinzaparin, an inhibitor of angiotensin converting enzyme and human serum albumin, a principal plasma protein in the liver has been investigated in vitro under a simulated physiological condition by UV-vis spectrophotometry and fluorescence spectrometry. The intrinsic fluorescence intensity of human serum albumin was strongly quenched by tinzaparin (TP). The binding constants and binding stoichiometry can be calculated from the data obtained from fluorescence quenching experiments. The negative value of ΔG° reveals that the binding process is a spontaneous process. Thermodynamic analysis shows that the HSA-TP complex formation occurs via hydrogen bonds, hydrophobic interactions and undergoes slight structural changes as evident by far-UV CD. It indicated that the hydrophobic interactions play a main role in the binding of TP to human serum albumin. In addition, the distance between TP (acceptor) and tryptophan residues of human serum albumin (donor) was estimated to be 2.21 nm according to the Förster's resonance energy transfer theory. For the deeper understanding of the interaction, thermodynamic, and molecular docking studies were performed as well. Our docking results suggest that TP forms stable complex with HSA (Kb ∼ 104) and its primary binding site is located in subdomain IIA (Sudlow Site I). The results obtained herein will be of biological significance in pharmacology and clinical medicine.

  14. Algorithms for Unequal-Arm Michelson Interferometers

    Science.gov (United States)

    Giampieri, Giacomo; Hellings, Ronald W.; Tinto, Massimo; Bender, Peter L.; Faller, James E.

    1994-01-01

    A method of data acquisition and data analysis is described in which the performance of Michelson-type interferometers with unequal arms can be made nearly the same as interferometers with equal arms. The method requires a separate readout of the relative phase in each arm, made by interfering the returning beam in each arm with a fraction of the outgoing beam.

  15. Improved Evolutionary Hybrids for Flexible Ligand Docking in Autodock

    Energy Technology Data Exchange (ETDEWEB)

    Belew, R.K.; Hart, W.E.; Morris, G.M.; Rosin, C.

    1999-01-27

    In this paper we evaluate the design of the hybrid evolutionary algorithms (EAs) that are currently used to perform flexible ligand binding in the Autodock docking software. Hybrid EAs incorporate specialized operators that exploit domain-specific features to accelerate an EA's search. We consider hybrid EAs that use an integrated local search operator to reline individuals within each iteration of the search. We evaluate several factors that impact the efficacy of a hybrid EA, and we propose new hybrid EAs that provide more robust convergence to low-energy docking configurations than the methods currently available in Autodock.

  16. The pickup and delivery problem with cross-docking opportunity

    DEFF Research Database (Denmark)

    Petersen, Hanne Løhmann; Røpke, Stefan

    2011-01-01

    In this paper, we consider the pickup and delivery problem with cross-docking opportunity (PDPCD). The problem arises from an industry application, and includes pickup requests, delivery requests, and pickup-and-delivery requests. Each pickup-and-delivery request can be served either as direct...... delivery by one truck, or by being picked up and transported to the cross-dock by one vehicle, and subsequently delivered at its final destination by another vehicle. Handling times at customers sites and terminal are given. A typical daily instance includes 500-1,000 requests. We solve the problem using...

  17. SYNTHESIS, DOCKING AND BIOLOGICAL STUDIES OF THE LINEAR TETRAPEPTIDE PWPV

    Directory of Open Access Journals (Sweden)

    M. Himaja

    2012-06-01

    Full Text Available Linear Tetrapeptides L-PWPV (Pro-Trp-Pro-Val was designed and synthesized by solution phase peptide synthesis based on dock score. The molecular docking studies of the designed tetrapeptide L-PWPV was carried out using Molegro Virtual Docker software for tumor cancer protein(1OLG. The linear tetrapeptide was synthesized by coupling protected amino acids (dipeptides using EDC (ethyl-3-(N,N-dimethylaminopropyl carbodiimide as coupling reagent. The compounds were analyzed by FTIR, 1H NMR and MASS data and subjected to antioxidant activity using 1,1-dipheny-2-picryl-hydrazil (DPPH method and insecticidal activity using Morita et al method.

  18. The Asteroid Redirect Mission (ARM): Exploration of a Former Binary NEA?

    Science.gov (United States)

    Abell, P. A.; Mazanek, D. D.; Reeves, D. M.; Chodas, P. W.; Gates, M. M.; Johnson, L. N.; Ticker, R. L.

    2016-01-01

    The National Aeronautics and Space Administration (NASA) is developing the Asteroid Redirect Mission (ARM) as a capability demonstration for future human exploration, including use of high-power solar electric propulsion, which allows for the efficient movement of large masses through deep space. The ARM will also demonstrate the capability to conduct proximity operations with natural space objects and crewed operations beyond the security of quick Earth return. The Asteroid Redirect Robotic Mission (ARRM), currently in formulation, will visit a large near-Earth asteroid (NEA), collect a multi-ton boulder from its surface, conduct a demonstration of a slow push planetary defense technique, and redirect the multi-ton boulder into a stable orbit around the Moon. Once returned to cislunar space in the mid-2020s, astronauts aboard an Orion spacecraft will dock with the robotic vehicle to explore the boulder and return samples to Earth. The ARM is part of NASA's plan to advance technologies, capabilities, and spaceflight experience needed for a human mission to the Martian system in the 2030s. The ARM and subsequent availability of the asteroidal material in cis-lunar space, provide significant opportunities to advance our knowledge of small bodies in the synergistic areas of science, planetary defense, and in-situ resource utilization (ISRU). The current reference target for the ARM is NEA (341843) 2008 EV5, which may have been the primary body of a former binary system (Busch et al., 2011; Tardivel et al., 2016). The ARRM will perform several close proximity operations to investigate the NEA and map its surface. A detailed investigation of this object may allow a better understanding of binary NEA physical characteristics and the possible outcomes for their evolution. An overview of the ARM robotic and crewed segments, including mission operations, and a discussion of potential opportunities for participation with the ARM will be provided in this presentation.

  19. Scheduling trucks in cross docking systems with temporary storage and dock repeat truck holding pattern using genetic algorithm

    Directory of Open Access Journals (Sweden)

    Ehsan Ghobadian

    2013-02-01

    Full Text Available Cross docking is one of the most important issues in management of supply chains. In cross docking, different items delivered to a warehouse by inbound trucks are directly arranged and reorganized based on customer demands, routed and loaded into outbound trucks for delivery purposes to customers without virtually keeping them at the warehouse. If any item is kept in storage, it is normally for a short amount of time, say less than 24 hours. In this paper, we consider a special case of cross docking where there is temporary storage and implements genetic algorithm to solve the resulted problem for some realistic test problems. In our method, we first use some heuristics as initial solutions and then improve the final solution using genetic algorithm. The performance of the proposed model is compared with alternative solution strategy, the GRASP method.

  20. Proprioceptive Interaction between the Two Arms in a Single-Arm Pointing Task.

    Directory of Open Access Journals (Sweden)

    Kazuyoshi Kigawa

    Full Text Available Proprioceptive signals coming from both arms are used to determine the perceived position of one arm in a two-arm matching task. Here, we examined whether the perceived position of one arm is affected by proprioceptive signals from the other arm in a one-arm pointing task in which participants specified the perceived position of an unseen reference arm with an indicator paddle. Both arms were hidden from the participant's view throughout the study. In Experiment 1, with both arms placed in front of the body, the participants received 70-80 Hz vibration to the elbow flexors of the reference arm (= right arm to induce the illusion of elbow extension. This extension illusion was compared with that when the left arm elbow flexors were vibrated or not. The degree of the vibration-induced extension illusion of the right arm was reduced in the presence of left arm vibration. In Experiment 2, we found that this kinesthetic interaction between the two arms did not occur when the left arm was vibrated in an abducted position. In Experiment 3, the vibration-induced extension illusion of one arm was fully developed when this arm was placed at an abducted position, indicating that the brain receives increased proprioceptive input from a vibrated arm even if the arm was abducted. Our results suggest that proprioceptive interaction between the two arms occurs in a one-arm pointing task when the two arms are aligned with one another. The position sense of one arm measured using a pointer appears to include the influences of incoming information from the other arm when both arms were placed in front of the body and parallel to one another.

  1. Spectroscopic and molecular docking techniques study of the interaction between oxymetholone and human serum albumin

    Energy Technology Data Exchange (ETDEWEB)

    Madrakian, Tayyebeh, E-mail: madrakian@basu.ac.ir; Bagheri, Habibollah; Afkhami, Abbas; Soleimani, Mohammad

    2014-11-15

    In this study, the binding of oxymetholone (OXM), a doping drug, to human serum albumin (HSA) was explored at pH 7.40 by spectroscopic methods including spectrofluorimetry, three dimensional excitation–emission matrix (3D EEM), UV–vis absorption, resonance rayleigh scattering (RRS) and molecular docking. The fluorescence results showed that there was a considerable quenching of the intrinsic fluorescence of HSA upon binding to OXM by static quenching mechanism. The Stern–Volmer quenching constants (K{sub SV}) between OXM and HSA at three different temperatures 295, 303, 308 K, were obtained as 4.63×10{sup 4}, 3.05×10{sup 4} and 1.49×10{sup 4} L mol{sup −1}, respectively. Furthermore this interaction was confirmed by UV–vis spectrophotometric and RRS techniques. The binding site number, n, apparent binding constant, K{sub b}, and corresponding thermodynamic parameters (ΔS, ΔH and ΔG) were measured at different temperatures. The Van der Waals and hydrogen-bond forces were found to stabilize OXM–HSA complex. The distance (r) between the donor and acceptor was obtained from Förster's theory of fluorescence resonance energy transfer (FRET) and found to be 1.67 nm. The 3D EEM showed that OXM slightly changes the secondary structure of HSA. Furthermore, the molecular docking was employed for identification of drug binding sites and interaction of OXM with amino acid residues. - Highlights: • The binding of OXM as a doping drug with HSA was studied by different techniques. • The binding constant of HSA–OXM was calculated. • The binding site of OXM on HSA was characterized with molecular docking. • The thermodynamic parameters were calculated according to fluorescence technique.

  2. MOLECULAR MODELING AND DOCKING STUDIES OF COLD ACTIVE LIPASE FROM Pseudomonas fluorescens

    Directory of Open Access Journals (Sweden)

    G. N. Gupta

    2015-03-01

    Full Text Available Molecular Modeling is essential tool in the drug design process describes the generation, manipulation or representation of 3D structures of the molecules and associated physico-chemical properties while docking predicts the preferred orientation of one molecule to a second when bound to each other to form a stable complex. A cold active lipase producing potential psychrophilic bacteria (GN was isolated and identified by 16S rRNA molecular studies as Pseudomonas vancouverensis. Lipase gene from closely related species P. fluorescens was investigated for their functional role and in silico characterization using molecular modeling and docking studies. A 3D structure of lipase gene was generated with SWISS-MODEL and Discovery Studio 3.0. The stereochemistry of the constructed model of cold active lipase was subjected to energy minimization and the stereo-chemical quality of the predicted structure was assessed. The superimposition of the template (PDBID: 2Z8X with predicted structure showed that weighted root mean square deviation of Cα trace between the template and the final refined model was 0.2 Å with a significant Zscore of 8.2 and sequence identity was 80.5%. Three ligands P-Nitrophenol, Acetate ion and Diethyl phosphonate were taken for docking calculation with generated structure. They were interacting on the functional motifs of predicted model. It has been observed that Leu26, Tyr29, Asn31, Asp33, Pro315 and Thr316 residues were involved in hydrogen bonding interactions with selected ligands. So these interacted residues can be used as prominent active binding sites and which was common to the predicted active site. Based on above investigations it has been found that P. vancouverensis lipase protein can play a similar role in lipid metabolic process and triglyceride lipase functional activity as reported for P. fluorescens lipase protein.

  3. Towards better modelling of drug-loading in solid lipid nanoparticles: Molecular dynamics, docking experiments and Gaussian Processes machine learning.

    Science.gov (United States)

    Hathout, Rania M; Metwally, Abdelkader A

    2016-11-01

    This study represents one of the series applying computer-oriented processes and tools in digging for information, analysing data and finally extracting correlations and meaningful outcomes. In this context, binding energies could be used to model and predict the mass of loaded drugs in solid lipid nanoparticles after molecular docking of literature-gathered drugs using MOE® software package on molecularly simulated tripalmitin matrices using GROMACS®. Consequently, Gaussian processes as a supervised machine learning artificial intelligence technique were used to correlate the drugs' descriptors (e.g. M.W., xLogP, TPSA and fragment complexity) with their molecular docking binding energies. Lower percentage bias was obtained compared to previous studies which allows the accurate estimation of the loaded mass of any drug in the investigated solid lipid nanoparticles by just projecting its chemical structure to its main features (descriptors).

  4. Economic Impacts from Spending by Community Dock Owners at Table Rock Lake

    Science.gov (United States)

    2008-01-01

    Rock Lake, community dock • Rough River Lake, community dock • Pomme de Terre Lake, community dock • Harry S. Truman Dam and Reservoir, marina...owners at Table Rock Lake (Missouri/Arkansas), Rough River Lake (Kentucky), and Pomme de Terre Lake (Missouri). The ERB staff designed the survey

  5. Novel Kidins220/ARMS Splice Isoforms: Potential Specific Regulators of Neuronal and Cardiovascular Development.

    Directory of Open Access Journals (Sweden)

    Nathalie Schmieg

    Full Text Available Kidins220/ARMS is a transmembrane protein playing a crucial role in neuronal and cardiovascular development. Kidins220/ARMS is a downstream target of neurotrophin receptors and interacts with several signalling and trafficking factors. Through computational modelling, we found two potential sites for alternative splicing of Kidins220/ARMS. The first is located between exon 24 and exon 29, while the second site replaces exon 32 by a short alternative terminal exon 33. Here we describe the conserved occurrence of several Kidins220/ARMS splice isoforms at RNA and protein levels. Kidins220/ARMS splice isoforms display spatio-temporal regulation during development with distinct patterns in different neuronal populations. Neurotrophin receptor stimulation in cortical and hippocampal neurons and neuroendocrine cells induces specific Kidins220/ARMS splice isoforms and alters the appearance kinetics of the full-length transcript. Remarkably, alternative terminal exon splicing generates Kidins220/ARMS variants with distinct cellular localisation: Kidins220/ARMS containing exon 32 is targeted to the plasma membrane and neurite tips, whereas Kidins220/ARMS without exon 33 mainly clusters the full-length protein in a perinuclear intracellular compartment in PC12 cells and primary neurons, leading to a change in neurotrophin receptor expression. Overall, this study demonstrates the existence of novel Kidins220/ARMS splice isoforms with unique properties, revealing additional complexity in the functional regulation of neurotrophin receptors, and potentially other signalling pathways involved in neuronal and cardiovascular development.

  6. Molecular dynamic and docking interaction study of Heterodera glycines serine proteinase with Vigna mungo proteinase inhibitor.

    Science.gov (United States)

    Prasad, C V S Siva; Gupta, Saurabh; Gaponenko, Alex; Tiwari, Murlidhar

    2013-08-01

    Many plants do produce various defense proteins like proteinase inhibitors (PIs) to protect them against various pests. PIs function as pseudosubstrates of digestive proteinase, which inhibits proteolysis in pests and leads to amino acid deficiency-based mortality. This work reports the structural interaction studies of serine proteinase of Heterodera glycines (SPHG) with Vigna mungo proteinase inhibitor (VMPI). 3D protein structure modeling, validation of SPHG and VMPI, and their putative protein-protein binding sites were predicted. Protein-protein docking followed by molecular dynamic simulation was performed to find the reliable confirmation of SPHG-VMPI complex. Trajectory analysis of each successive conformation concludes better interaction of first loop in comparison with second loop. Lysine residues of first loop were actively participating in complex formation. Overall, this study discloses the structural aspects and interaction mechanisms of VMPI with SPHG, and it would be helpful in the development of pest-resistant genetically modified crops.

  7. Scanning ARM Cloud Radar Handbook

    Energy Technology Data Exchange (ETDEWEB)

    Widener, K; Bharadwaj, N; Johnson, K

    2012-06-18

    The scanning ARM cloud radar (SACR) is a polarimetric Doppler radar consisting of three different radar designs based on operating frequency. These are designated as follows: (1) X-band SACR (X-SACR); (2) Ka-band SACR (Ka-SACR); and (3) W-band SACR (W-SACR). There are two SACRs on a single pedestal at each site where SACRs are deployed. The selection of the operating frequencies at each deployed site is predominantly determined by atmospheric attenuation at the site. Because RF attenuation increases with atmospheric water vapor content, ARM's Tropical Western Pacific (TWP) sites use the X-/Ka-band frequency pair. The Southern Great Plains (SGP) and North Slope of Alaska (NSA) sites field the Ka-/W-band frequency pair. One ARM Mobile Facility (AMF1) has a Ka/W-SACR and the other (AMF2) has a X/Ka-SACR.

  8. Application of the docking program SOL for CSAR benchmark.

    Science.gov (United States)

    Sulimov, Alexey V; Kutov, Danil C; Oferkin, Igor V; Katkova, Ekaterina V; Sulimov, Vladimir B

    2013-08-26

    This paper is devoted to results obtained by the docking program SOL and the post-processing program DISCORE at the CSAR benchmark. SOL and DISCORE programs are described. SOL is the original docking program developed on the basis of the genetic algorithm, MMFF94 force field, rigid protein, precalculated energy grid including desolvation in the frame of simplified GB model, vdW, and electrostatic interactions and taking into account the ligand internal strain energy. An important SOL feature is the single- or multi-processor performance for up to hundreds of CPUs. DISCORE improves the binding energy scoring by the local energy optimization of the ligand docked pose and a simple linear regression on the base of available experimental data. The docking program SOL has demonstrated a good ability for correct ligand positioning in the active sites of the tested proteins in most cases of CSAR exercises. SOL and DISCORE have not demonstrated very exciting results on the protein-ligand binding free energy estimation. Nevertheless, for some target proteins, SOL and DISCORE were among the first in prediction of inhibition activity. Ways to improve SOL and DISCORE are discussed.

  9. System for deflection measurements of floating dry docks

    Science.gov (United States)

    Gorbachev, Alexey A.; Pantyushin, Anton V.; Serikova, Mariya G.; Korotaev, Valery V.; Timofeev, Aleksandr N.

    2015-05-01

    In this paper we introduce a system for deflection measurement of floating dry docks. The system contains two measurement channels observing opposite directions of the dock. It also includes set of reference marks, an industrial computer and a display. Each channel contains CMOS camera with long focal-length lens. Reference marks are implemented as IR LED arrays with 940 nm working wavelength for better performance within bad weather conditions (e.g. fog, rain, high humidity etc.). In the paper we demonstrate results of an analysis of different optical schemes for coupling the oppositely directed channels of the measurement unit and show that the scheme with two image sensors with separated lenses is an optimal option, because it allows usage of nonequidistant location of reference marks and demonstrates the least value of parasitic shift caused by rotations of the measuring unit. The developed system was tested both on specially-designed setup and in real infrastructure of a floating dry dock. The conducted tests proved that a measuring error of the system is smaller than +/- 1.5 mm within the measurement range of +/- 150 mm when deflection of 100 m dock is measured. Obtained results showed that the system demonstrates an ability to work in a harsh environment including poor weather conditions.

  10. Spacecraft Rendevouz and Docking. An Autonomy assisted Human Operator Approach

    DEFF Research Database (Denmark)

    Jørgensen, John Leif; Thuesen, Gøsta

    1999-01-01

    The phenomena and problems encountered when a rendezvous maneuver, and possible docking, of two spacecrafts has to be performed, have been the topic for numerous studies and details of a variety of scenarios has been analyzed. So far, all solutions that have been brought into realization have bee...

  11. Dissecting Nck/Dock Signaling Pathways in Drosophila Visual System

    Directory of Open Access Journals (Sweden)

    2005-04-01

    Full Text Available The establishment of neuronal connections during embryonic development requires the precise guidance and targeting of the neuronal growth cone, an expanded cellular structure at the leading tip of a growing axon. The growth cone contains sophisticated signaling systems that allow the rapid communication between guidance receptors and the actin cytoskeleton in generating directed motility. Previous studies demonstrated a specific role for the Nck/Dock SH2/SH3 adapter protein in photoreceptor (R cell axon guidance and target recognition in the Drosophila visual system, suggesting strongly that Nck/Dock is one of the long-sought missing links between cell surface receptors and the actin cytoskeleton. In this review, I discuss the recent progress on dissecting the Nck/Dock signaling pathways in R-cell growth cones. These studies have identified additional key components of the Nck/Dock signaling pathways for linking the receptor signaling to the remodeling of the actin cytoskeleton in controlling growth-cone motility.

  12. Normal mode-based approaches in receptor ensemble docking.

    Science.gov (United States)

    Cavasotto, Claudio N

    2012-01-01

    Explicitly accounting for target flexibility in docking still constitutes a difficult challenge due to the high dimensionality of the conformational space to be sampled. This especially applies to the high-throughput scenario, where the screening of hundreds of thousands compounds takes place. The use of multiple receptor conformations (MRCs) to perform ensemble docking in a sequential fashion is a simple but powerful approach that allows to incorporate binding site structural diversity in the docking process. Whenever enough experimental structures to build a diverse ensemble are not available, normal mode analysis provides an appealing and efficient approach to in silico generate MRCs by distortion along few low-frequency modes that represent collective mid- and large-scale displacements. In this way, the dimension of the conformational space to be sampled is heavily reduced. This methodology is especially suited to incorporate target flexibility at the backbone level. In this chapter, the main components of normal mode-based approaches in the context of ensemble docking are presented and explained, including the theoretical and practical considerations needed for the successful development and implementation of this methodology.

  13. Docking Studies of Binding of Ethambutol to the C-Terminal Domain of the Arabinosyltransferase from Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Guillermo Salgado-Moran

    2013-01-01

    Full Text Available The binding of ethambutol to the C-terminal domain of the arabinosyltransferase from Mycobacterium tuberculosis was studied. The analysis was performed using an in silico approach in order to find out, by docking calculations and energy descriptors, the conformer of Ethambutol that forms the most stable complex with the C-terminal domain of arabinosyltransferase. The complex shows that location of the Ethambutol coincides with the cocrystallization ligand position and that amino acid residues ASH1051, ASN740, ASP1052, and ARG1055 should be critical in the binding of Ethambutol to C-terminal domain EmbC.

  14. Tail Docking and Ear Cropping Dogs: Public Awareness and Perceptions.

    Directory of Open Access Journals (Sweden)

    Katelyn E Mills

    Full Text Available Tail docking and ear cropping are two surgical procedures commonly performed on many dog breeds. These procedures are classified as medically unnecessary surgeries whose purpose is primarily cosmetic. Available attitude research surrounding these controversial practices has been limited to surveys of veterinarians and dog breeders familiar with both practices. The aim of this project was to: 1 assess public awareness of tail docking and ear cropping, 2 determine whether physical alteration of a dog affects how the dog, and 3 owner are perceived. In Experiment 1 awareness was measured using a combination of both explicit and implicit measures. We found that 42% of participants (n = 810 were unable to correctly explain the reason why tail docked and ear cropped dogs had short ears and tails. Similarly, an implicit measure of awareness ('nature vs nurture task', found that the majority of participants believed short tails and erect ears were a consequence of genetics rather than something the owner or breeder had done. The results obtained in Experiment 2 (n = 392 provide evidence that ear cropped and tail docked dogs are perceived differently than an identical dog in its 'natural' state. Modified dogs were perceived as being more aggressive, more dominant, less playful and less attractive than natural dogs. Experiment 3 (n = 410 is the first evidence that owners of modified dogs are perceived as being more aggressive, more narcissistic, less playful, less talkative and less warm compared to owners of natural dogs. Taken together, these results suggest that although a significant proportion of subjects appear unaware of the practices of tail docking and ear cropping in dogs, these procedures have significant impacts on how modified dogs and their owners are perceived by others.

  15. Tail Docking and Ear Cropping Dogs: Public Awareness and Perceptions

    Science.gov (United States)

    Mills, Katelyn E.; Robbins, Jesse; von Keyserlingk, Marina A. G.

    2016-01-01

    Tail docking and ear cropping are two surgical procedures commonly performed on many dog breeds. These procedures are classified as medically unnecessary surgeries whose purpose is primarily cosmetic. Available attitude research surrounding these controversial practices has been limited to surveys of veterinarians and dog breeders familiar with both practices. The aim of this project was to: 1) assess public awareness of tail docking and ear cropping, 2) determine whether physical alteration of a dog affects how the dog, and 3) owner are perceived. In Experiment 1 awareness was measured using a combination of both explicit and implicit measures. We found that 42% of participants (n = 810) were unable to correctly explain the reason why tail docked and ear cropped dogs had short ears and tails. Similarly, an implicit measure of awareness (‘nature vs nurture task’), found that the majority of participants believed short tails and erect ears were a consequence of genetics rather than something the owner or breeder had done. The results obtained in Experiment 2 (n = 392) provide evidence that ear cropped and tail docked dogs are perceived differently than an identical dog in its ‘natural’ state. Modified dogs were perceived as being more aggressive, more dominant, less playful and less attractive than natural dogs. Experiment 3 (n = 410) is the first evidence that owners of modified dogs are perceived as being more aggressive, more narcissistic, less playful, less talkative and less warm compared to owners of natural dogs. Taken together, these results suggest that although a significant proportion of subjects appear unaware of the practices of tail docking and ear cropping in dogs, these procedures have significant impacts on how modified dogs and their owners are perceived by others. PMID:27348817

  16. Tail Docking and Ear Cropping Dogs: Public Awareness and Perceptions.

    Science.gov (United States)

    Mills, Katelyn E; Robbins, Jesse; von Keyserlingk, Marina A G

    2016-01-01

    Tail docking and ear cropping are two surgical procedures commonly performed on many dog breeds. These procedures are classified as medically unnecessary surgeries whose purpose is primarily cosmetic. Available attitude research surrounding these controversial practices has been limited to surveys of veterinarians and dog breeders familiar with both practices. The aim of this project was to: 1) assess public awareness of tail docking and ear cropping, 2) determine whether physical alteration of a dog affects how the dog, and 3) owner are perceived. In Experiment 1 awareness was measured using a combination of both explicit and implicit measures. We found that 42% of participants (n = 810) were unable to correctly explain the reason why tail docked and ear cropped dogs had short ears and tails. Similarly, an implicit measure of awareness ('nature vs nurture task'), found that the majority of participants believed short tails and erect ears were a consequence of genetics rather than something the owner or breeder had done. The results obtained in Experiment 2 (n = 392) provide evidence that ear cropped and tail docked dogs are perceived differently than an identical dog in its 'natural' state. Modified dogs were perceived as being more aggressive, more dominant, less playful and less attractive than natural dogs. Experiment 3 (n = 410) is the first evidence that owners of modified dogs are perceived as being more aggressive, more narcissistic, less playful, less talkative and less warm compared to owners of natural dogs. Taken together, these results suggest that although a significant proportion of subjects appear unaware of the practices of tail docking and ear cropping in dogs, these procedures have significant impacts on how modified dogs and their owners are perceived by others.

  17. Autonomous Vision-Based Tethered-Assisted Rover Docking

    Science.gov (United States)

    Tsai, Dorian; Nesnas, Issa A.D.; Zarzhitsky, Dimitri

    2013-01-01

    Many intriguing science discoveries on planetary surfaces, such as the seasonal flows on crater walls and skylight entrances to lava tubes, are at sites that are currently inaccessible to state-of-the-art rovers. The in situ exploration of such sites is likely to require a tethered platform both for mechanical support and for providing power and communication. Mother/daughter architectures have been investigated where a mother deploys a tethered daughter into extreme terrains. Deploying and retracting a tethered daughter requires undocking and re-docking of the daughter to the mother, with the latter being the challenging part. In this paper, we describe a vision-based tether-assisted algorithm for the autonomous re-docking of a daughter to its mother following an extreme terrain excursion. The algorithm uses fiducials mounted on the mother to improve the reliability and accuracy of estimating the pose of the mother relative to the daughter. The tether that is anchored by the mother helps the docking process and increases the system's tolerance to pose uncertainties by mechanically aligning the mating parts in the final docking phase. A preliminary version of the algorithm was developed and field-tested on the Axel rover in the JPL Mars Yard. The algorithm achieved an 80% success rate in 40 experiments in both firm and loose soils and starting from up to 6 m away at up to 40 deg radial angle and 20 deg relative heading. The algorithm does not rely on an initial estimate of the relative pose. The preliminary results are promising and help retire the risk associated with the autonomous docking process enabling consideration in future martian and lunar missions.

  18. A combinatorial scoring function for protein-RNA docking.

    Science.gov (United States)

    Zhang, Zhao; Lu, Lin; Zhang, Yue; Hua Li, Chun; Wang, Cun Xin; Zhang, Xiao Yi; Tan, Jian Jun

    2017-04-01

    Protein-RNA docking is still an open question. One of the main challenges is to develop an effective scoring function that can discriminate near-native structures from the incorrect ones. To solve the problem, we have constructed a knowledge-based residue-nucleotide pairwise potential with secondary structure information considered for nonribosomal protein-RNA docking. Here we developed a weighted combined scoring function RpveScore that consists of the pairwise potential and six physics-based energy terms. The weights were optimized using the multiple linear regression method by fitting the scoring function to L_rmsd for the bound docking decoys from Benchmark II. The scoring functions were tested on 35 unbound docking cases. The results show that the scoring function RpveScore including all terms performs best. Also RpveScore was compared with the statistical mechanics-based method derived potential ITScore-PR, and the united atom-based statistical potentials QUASI-RNP and DARS-RNP. The success rate of RpveScore is 71.6% for the top 1000 structures and the number of cases where a near-native structure is ranked in top 30 is 25 out of 35 cases. For 32 systems (91.4%), RpveScore can find the binding mode in top 5 that has no lower than 50% native interface residues on protein and nucleotides on RNA. Additionally, it was found that the long-range electrostatic attractive energy plays an important role in distinguishing near-native structures from the incorrect ones. This work can be helpful for the development of protein-RNA docking methods and for the understanding of protein-RNA interactions. RpveScore program is available to the public at http://life.bjut.edu.cn/kxyj/kycg/2017116/14845362285362368_1.html Proteins 2017; 85:741-752. © 2016 Wiley Periodicals, Inc.

  19. Spectrofluoremetric and molecular docking study on the interaction of bisdemethoxycurcumin with bovine β-casein nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Mehranfar, Fahimeh [Department of Chemistry, University of Isfahan, Isfahan 81746-73441 (Iran, Islamic Republic of); Bordbar, Abdol-Khalegh, E-mail: bordbar@chem.ui.ac.ir [Department of Chemistry, University of Isfahan, Isfahan 81746-73441 (Iran, Islamic Republic of); Keyhanfar, Mehrnaz; Behbahani, Mandana [Faculty of Advanced Sciences and Technologies, Department of Biotechnology, University of Isfahan, Isfahan, 81746-73441 (Iran, Islamic Republic of)

    2013-11-15

    The interaction of bisdemethoxycurcumin (BDMC), as one of the main active component of turmeric (Curcuma longa L.), with bovine β-casein nanoparticle, as an efficient drug carrier system, was investigated using steady-state fluorescence spectroscopy and molecular docking calculations. Results of fluorescence quenching experiments, Forster energy transfer measurements and molecular docking calculations suggested that BDMC bind to the hydrophobic core of β-casein via formation of 3 hydrogen bonds and several vander Waals contacts that represented the encapsulation of BDMC in β-casein micelle nanoparticles. The binding parameters including number of substantive binding sites and the binding constants were evaluated by fluorescence quenching method. Additionally, the cytotoxicity of free BDMC and BDMC-β-casein complex in human breast cancer cell line MCF7 was evaluated in vitro. The study revealed the higher cytotoxic effects of encapsulated BDMC on MCF7 cells compared to equal dose of free BDMC. -- Highlights: • BDMC binds to the hydrophobic core of β-casein. • The effective encapsulation of BDMC in β-casein micelle nanoparticles was shown. • Enhanced cytotoxicity was observed for encapsulated BDMC in β-casein nanoparticles.

  20. Combined Docking and Quantum Chemical Study on CYP-Mediated Metabolism of Estrogens in Man.

    Science.gov (United States)

    Lábas, Anikó; Krámos, Balázs; Oláh, Julianna

    2017-02-20

    Long-term exposure to estrogens seriously increases the incidence of various diseases including breast cancer. Experimental studies indicate that cytochrome P450 (CYP) enzymes catalyze the bioactivation of estrogens to catechols, which can exert their harmful effects via various routes. It has been shown that the 4-hydroxylation pathway of estrogens is the most malign, while 2-hydroxylation is considered a benign pathway. It is also known experimentally that with increasing unsaturation of ring B of estrogens the prevalence of the 4-hydroxylation pathway significantly increases. In this study, we used a combination of structural analysis, docking, and quantum chemical calculations at the B3LYP/6-311+G* level to investigate the factors that influence the regioselectivity of estrogen metabolism in man. We studied the structure of human estrogen metabolizing enzymes (CYP1A1, CYP1A2, CYP1B1, and CYP3A4) in complex with estrone using docking and investigated the susceptibility of estrone, equilin, and equilenin (which only differ in the unsaturation of ring B) to undergo 2- and 4-hydroxylation using several models of CYP enzymes (Compound I, methoxy, and phenoxy radical). We found that even the simplest models could account for the experimental difference between the 2- and 4- hydroxylation pathways and thus might be used for fast screening purposes. We also show that reactivity indices, specifically in this case the radical and nucleophilic condensed Fukui functions, also correctly predict the likeliness of estrogen derivatives to undergo 2- or 4-hydroxylation.

  1. Human nucleoporins promote HIV-1 docking at the nuclear pore, nuclear import and integration.

    Directory of Open Access Journals (Sweden)

    Francesca Di Nunzio

    Full Text Available The nuclear pore complex (NPC mediates nucleo-cytoplasmic transport of macromolecules and is an obligatory point of passage and functional bottleneck in the replication of some viruses. The Human Immunodeficiency Virus (HIV has evolved the required mechanisms for active nuclear import of its genome through the NPC. However the mechanisms by which the NPC allows or even assists HIV translocation are still unknown. We investigated the involvement of four key nucleoporins in HIV-1 docking, translocation, and integration: Nup358/RanBP2, Nup214/CAN, Nup98 and Nup153. Although all induce defects in infectivity when depleted, only Nup153 actually showed any evidence of participating in HIV-1 translocation through the nuclear pore. We show that Nup358/RanBP2 mediates docking of HIV-1 cores on NPC cytoplasmic filaments by interacting with the cores and that the C-terminus of Nup358/RanBP2 comprising a cyclophilin-homology domain contributes to binding. We also show that Nup214/CAN and Nup98 play no role in HIV-1 nuclear import per se: Nup214/CAN plays an indirect role in infectivity read-outs through its effect on mRNA export, while the reduction of expression of Nup98 shows a slight reduction in proviral integration. Our work shows the involvement of nucleoporins in diverse and functionally separable steps of HIV infection and nuclear import.

  2. Synthesis of novel bisindolylmethanes: New carbonic anhydrase II inhibitors, docking, and 3D pharmacophore studies.

    Science.gov (United States)

    Imran, Syahrul; Taha, Muhammad; Ismail, Nor Hadiani; Fayyaz, Sharmeen; Khan, Khalid Mohammed; Choudhary, Muhammad Iqbal

    2016-10-01

    In this study, 45 bisindolylmethanes having sulfonamide moiety had been synthesized through 3 steps. In vitro assay for inhibition of carbonic anhydrase showed that some of the compounds having sulfonamide moiety are capable of inhibiting carbonic anhydrase II. Bisindoles having halogens at fifth position showed better inhibitory activity as compared to unsubstituted bisindoles. The results obtained from in vitro inhibitory activity were subjected through 3D QSAR and docking studies to identify important features contributing to the activity and further improve the structure. Pharmacophore studies suggest that bisindolylmethane moiety is contributing significantly towards the inhibition activity. Docking studies showed that compounds having nitro substituent (5g and 5i) were found to be able interact with Zn(2+) ion, Thr199, His94, His96, and His119, which interferes with the ZnOHThr199Glu106 hydrogen bond network. Bulky nitro substituent at ortho position for compound 5g prevents the compound from interacting with other residues like Thr199 and Thr200. Methyl substituent at ortho position for Compound 5i induces less steric hindrance effect, thus allowing second oxygen atom of sulfonamide to interact with Thr199 (2.51Å). Hydrogen bonding between NH on indole ring with Glu69 might have increased stability of ligand-receptor complex.

  3. Molecular docking as a popular tool in drug design, an in silico travel

    Directory of Open Access Journals (Sweden)

    de Ruyck J

    2016-06-01

    Full Text Available Jerome de Ruyck, Guillaume Brysbaert, Ralf Blossey, Marc F Lensink University Lille, CNRS UMR8576 UGSF, Lille, FranceAbstract: New molecular modeling approaches, driven by rapidly improving computational platforms, have allowed many success stories for the use of computer-assisted drug design in the discovery of new mechanism- or structure-based drugs. In this overview, we highlight three aspects of the use of molecular docking. First, we discuss the combination of molecular and quantum mechanics to investigate an unusual enzymatic mechanism of a flavoprotein. Second, we present recent advances in anti-infectious agents' synthesis driven by structural insights. At the end, we focus on larger biological complexes made by protein–protein interactions and discuss their relevance in drug design. This review provides information on how these large systems, even in the presence of the solvent, can be investigated with the outlook of drug discovery.Keywords: structure-based drug design, protein–protein docking, quaternary structure prediction, residue interaction networks, RINs, water position

  4. Caffeine and sulfadiazine interact differently with human serum albumin: A combined fluorescence and molecular docking study

    Science.gov (United States)

    Islam, Mullah Muhaiminul; Sonu, Vikash K.; Gashnga, Pynsakhiat Miki; Moyon, N. Shaemningwar; Mitra, Sivaprasad

    2016-01-01

    The interaction and binding behavior of the well-known drug sulfadiazine (SDZ) and psychoactive stimulant caffeine (CAF) with human serum albumin (HSA) was monitored by in vitro fluorescence titration and molecular docking calculations under physiological condition. The quenching of protein fluorescence on addition of CAF is due to the formation of protein-drug complex in the ground state; whereas in case of SDZ, the experimental results were explained on the basis of sphere of action model. Although both these compounds bind preferentially in Sudlow's site 1 of the protein, the association constant is approximately two fold higher in case of SDZ (∼4.0 × 104 M-1) in comparison with CAF (∼9.3 × 102 M-1) and correlates well with physico-chemical properties like pKa and lipophilicity of the drugs. Temperature dependent fluorescence study reveals that both SDZ and CAF bind spontaneously with HSA. However, the binding of SDZ with the protein is mainly governed by the hydrophobic forces in contrast with that of CAF; where, the interaction is best explained in terms of electrostatic mechanism. Molecular docking calculation predicts the binding of these drugs in different location of sub-domain IIA in the protein structure.

  5. Arms control and international security

    Energy Technology Data Exchange (ETDEWEB)

    Kolkowicz, R. (ed.); Joeck, N.

    1984-01-01

    This book compiles the papers delivered at a symposium held at the University of California, in 1983. It provides the discussions upon the value and importance of arms debate. The paper presents an expression of personal views rather than an analysis of the arguments of the primary presentations.

  6. Nuclear physicist, arms control advocate

    CERN Multimedia

    Chang, K

    2002-01-01

    Victor F. Weisskopf, a nuclear physicist who worked on the Manhattan Project to build the first atomic bomb in World War II and later became an ardent advocate of arms control, died Monday at his home in Newton, MA, USA. He was 93 (1 page).

  7. Hand/Wrist/Arm Problems

    Science.gov (United States)

    ... your doctor right away.Start OverDiagnosisYou may have TENDINITIS, inflammation of a tendon.Self CareUse an over- ... OverDiagnosisYour may have TENNIS ELBOW, a type of TENDINITIS.Self CareRest the arm, apply ice packs to ...

  8. Complexation of Bi{sup 3+}, Ac{sup 3+}, Y{sup 3+}, Lu{sup 3+}, La{sup 3+} and Eu{sup 3+} with benzo-diaza-crown ether with carboxylic pendant arms

    Energy Technology Data Exchange (ETDEWEB)

    Egorova, Bayirta V. [Lomonosov Moscow State Univ., Moscow (Russian Federation). Chemistry Dept.; Oshchepkov, Maxim S.; Fedorova, Olga A. [Mendeleev University of Chemistry and Technology of Russia, Moscow (Russian Federation); Russian Academy of Sciences, Moscow (Russian Federation). A.N. Nesmeyanov Institute of Organoelement Compounds; Fedorov, Yury V. [Lomonosov Moscow State Univ., Moscow (Russian Federation). Chemistry Dept.; Russian Academy of Sciences, Moscow (Russian Federation). A.N. Nesmeyanov Institute of Organoelement Compounds; Budylin, Gleb S.; Shirshin, Evgeny A. [Lomonosov Moscow State Univ., Moscow (Russian Federation). Dept. of Physics; Kalmykov, Stepan N. [Lomonosov Moscow State Univ., Moscow (Russian Federation). Chemistry Dept.; National Research Center ' Kurchatov Institute' , Moscow (Russian Federation)

    2016-11-01

    Polyaminopolycarboxylates are attractive ligands for binding cationic radionuclides for synthesis of radiopharmaceuticals with target delivery to tumor cells. Nowadays beta emitting Y-90 and Lu-177 are used as therapeutic agents, while Ac-225 and Bi-213 are considered as perspective for alpha therapy. In the present study new data on complexation of Y{sup 3+}, Lu{sup 3+}, Ac{sup 3+} and Bi{sup 3+} with 2,2'-(15-formyl-2,3,5,6,8,9,11,12-octahydrobenzo [b][1,4,10,7,13]trioxadiazacyclopentadecine-4,10- diyl)diacetic acid are presented. For ligand and complexes characterization potentiometric titration, solvent extraction, chromatography and solubility techniques were applied. The highest values of stability constants within the range of log K = 5.8 - 7.5 were found for Ac{sup 3+} and REE. Fast complex formation is established which is beneficial for practical applications in radiopharmaceutical synthesis.

  9. Characterization of a Family with Rare Deletions in CNTNAP5 and DOCK4 Suggests Novel Risk Loci for Autism and Dyslexia

    Science.gov (United States)

    Pagnamenta, Alistair T.; Bacchelli, Elena; de Jonge, Maretha V.; Mirza, Ghazala; Scerri, Thomas S.; Minopoli, Fiorella; Chiocchetti, Andreas; Ludwig, Kerstin U.; Hoffmann, Per; Paracchini, Silvia; Lowy, Ernesto; Harold, Denise H.; Chapman, Jade A.; Klauck, Sabine M.; Poustka, Fritz; Houben, Renske H.; Staal, Wouter G.; Ophoff, Roel A.; O'Donovan, Michael C.; Williams, Julie; Nöthen, Markus M.; Schulte-Körne, Gerd; Deloukas, Panos; Ragoussis, Jiannis; Bailey, Anthony J.; Maestrini, Elena; Monaco, Anthony P.

    2010-01-01

    Background Autism spectrum disorders (ASDs) are characterized by social, communication, and behavioral deficits and complex genetic etiology. A recent study of 517 ASD families implicated DOCK4 by single nucleotide polymorphism (SNP) association and a microdeletion in an affected sibling pair. Methods The DOCK4 microdeletion on 7q31.1 was further characterized in this family using QuantiSNP analysis of 1M SNP array data and reverse transcription polymerase chain reaction. Extended family members were tested by polymerase chain reaction amplification of junction fragments. DOCK4 dosage was measured in additional samples using SNP arrays. Since QuantiSNP analysis identified a novel CNTNAP5 microdeletion in the same affected sibling pair, this gene was sequenced in 143 additional ASD families. Further polymerase chain reaction-restriction fragment length polymorphism analysis included 380 ASD cases and suitable control subjects. Results The maternally inherited microdeletion encompassed chr7:110,663,978-111,257,682 and led to a DOCK4-IMMP2L fusion transcript. It was also detected in five extended family members with no ASD. However, six of nine individuals with this microdeletion had poor reading ability, which prompted us to screen 606 other dyslexia cases. This led to the identification of a second DOCK4 microdeletion co-segregating with dyslexia. Assessment of genomic background in the original ASD family detected a paternal 2q14.3 microdeletion disrupting CNTNAP5 that was also transmitted to both affected siblings. Analysis of other ASD cohorts revealed four additional rare missense changes in CNTNAP5. No exonic deletions of DOCK4 or CNTNAP5 were seen in 2091 control subjects. Conclusions This study highlights two new risk factors for ASD and dyslexia and demonstrates the importance of performing a high-resolution assessment of genomic background, even after detection of a rare and likely damaging microdeletion using a targeted approach. PMID:20346443

  10. Virtual fragment screening: an exploration of various docking and scoring protocols for fragments using Glide

    Science.gov (United States)

    Kawatkar, Sameer; Wang, Hongming; Czerminski, Ryszard; Joseph-McCarthy, Diane

    2009-08-01

    Fragment-based drug discovery approaches allow for a greater coverage of chemical space and generally produce high efficiency ligands. As such, virtual and experimental fragment screening are increasingly being coupled in an effort to identify new leads for specific therapeutic targets. Fragment docking is employed to create target-focussed subset of compounds for testing along side generic fragment libraries. The utility of the program Glide with various scoring schemes for fragment docking is discussed. Fragment docking results for two test cases, prostaglandin D2 synthase and DNA ligase, are presented and compared to experimental screening data. Self-docking, cross-docking, and enrichment studies are performed. For the enrichment runs, experimental data exists indicating that the docking decoys in fact do not inhibit the corresponding enzyme being examined. Results indicate that even for difficult test cases fragment docking can yield enrichments significantly better than random.

  11. Para-(benzoyl)-phenylalanine as a potential inhibitor against LpxC of Leptospira spp.: homology modeling, docking, and molecular dynamics study.

    Science.gov (United States)

    Pradhan, Dibyabhaba; Priyadarshini, Vani; Munikumar, Manne; Swargam, Sandeep; Umamaheswari, Amineni; Bitla, Aparna

    2014-01-01

    Leptospira interrogans, a Gram-negative bacterial pathogen is the main cause of human leptospirosis. Lipid A is a highly immunoreactive endotoxic center of lipopolysaccharide (LPS) that anchors LPS into the outer membrane of Leptospira. Discovery of compounds inhibiting lipid-A biosynthetic pathway would be promising for dissolving the structural integrity of membrane leading to cell lysis and death of Leptospira. LpxC, a unique enzyme of lipid-A biosynthetic pathway was identified as common drug target of Leptospira. Herein, homology modeling, docking, and molecular dynamics (MD) simulations were employed to discover potential inhibitors of LpxC. A reliable tertiary structure of LpxC in complex with inhibitor BB-78485 was constructed in Modeller 9v8. A data-set of BB-78485 structural analogs were docked with LpxC in Maestro v9.2 virtual screening workflow, which implements three stage Glide docking protocol. Twelve lead molecules with better XP Gscore compared to BB-78485 were proposed as potential inhibitors of LpxC. Para-(benzoyl)-phenylalanine - that showed lowest XP Gscore (-10.35 kcal/mol) - was predicted to have best binding affinity towards LpxC. MD simulations were performed for LpxC and para-(benzoyl)-phenylalanine docking complex in Desmond v3.0. Trajectory analysis showed the docking complex and inter-molecular interactions was stable throughout the entire production part of MD simulations. The results indicate para-(benzoyl)-phenylalanine as a potent drug molecule against leptospirosis. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:JBSD:10.

  12. Design of an Automatic Autonomous Mini Prone-cone Microsatellite Docking Mechanism

    Institute of Scientific and Technical Information of China (English)

    LAI Yinan; DAI Ye; TIAN Hao; ZHANG Dawei

    2010-01-01

    The capability of docking, refueling, repairing, and updating microsatellites using automatic autonomous vehicles will be of significance critical value for design and operation of several space systems in the near feature. Automatic docking capability was successfully tested by many institutions such as National Space Development Agency in Japan, European Space Agency, National Aeronautics and Space Administration in USA, etc. However, there is still much more space for improvement of degree of automation during the process of docking with large deviations of the initial attitude. A novel automatic autonomous probe-cone docking mechanism used for microsatellite docking is proposed. This docking mechanism is designed according to the design indices such as miniaturization, degree of automation and automatic capture capability within large deviation of the initial attitude. On the basis of the virtual work principle, the dynamics modeling of the docking process is presented. The position of the contact point is then analyzed. Comprehensive system level simulation is conducted in the 13 kinds of typical operating conditions with the initial deviations. Capture performance is analyzed. The simulation results show that the docking mechanism can be smoothly captured within 2 s in all cases of large attitude deviation between the active and passive spacecrafts. A virtual prototype model of the docking mechanism is established through ADAMS for further verifying the correctness of the buffer parameter model and the autonomous docking capability. A laboratory platform is designed for on-the-ground experimental validation of the property of mini probe-cone docking mechanism. Repeated docking tests prove the proposed design of the mini probe-cone docking mechanism system for its high reliability, and automatic capture capability within large attitude range. The kinetic model of the docking capture process and the mechanism structure could provide some References for similar

  13. Dinuclear Cu(II) complexes of compartmental Schiff base ligands formed from unsymmetrical tripodal amines of varying arm lengths: Crystal structure of [Cu2L1](ClO4)2 and theoretical studies

    Science.gov (United States)

    Keypour, Hassan; Shayesteh, Maryam; Rezaeivala, Majid; Sayin, Koray

    2016-05-01

    Three new dinuclear copper complexes were synthesized via condensation reaction of three new unsymmetrical N-capped tripodal amines and 2,6-diformyl-4-methylphenol, in the presence of copper(II) perchlorate. The solid-state structure of the dinuclear complex, [Cu2L1](ClO4)2, has been determined by X-ray crystallography, showing that the CuII centers have distorted square-pyramidal geometry with N3O2 coordination. The copper (II) ions are bridged by phenolic and hydroxyalkyl groups when in both cases, deprotonation of the hydrogen atoms of the OH groups occurs. The distance between the copper atoms is 3.062 Å. This compound consists of the dication [Cu2L1]2+ and two ClO4- anions in which one of ClO4- groups has a week interaction with one of the Cu atoms. All complexes were characterized by a variety of physico-chemical techniques such as elemental analyses, IR, mass spectra, conductivity measurements and electronic spectral studies. Computational investigation of mentioned binuclear Cu(II) complexes was done by using M062X method with LANL2DZ basis set in vacuo.

  14. Synthesis and structural determination of zinc complexes based on an anilido-aldimine ligand containing an O-donor pendant arm: zinc alkoxide derivative as an efficient initiator for ring-opening polymerization of cyclic esters.

    Science.gov (United States)

    Wang, Chao-Hsiang; Li, Chen-Yu; Huang, Bor-Hunn; Lin, Chu-Chieh; Ko, Bao-Tsan

    2013-08-14

    Zinc complexes bearing the anilido-aldiminate AA(OMe) ligand (AA(OMe)-H = (E)-2,6-diisopropyl-N-(2-(((2-methoxyethyl)imino)methyl)phenyl)aniline) were synthesized in a stepwise method and were structurally characterized. The reaction of AA(OMe)-H (1) with one equivalent of diethyl zinc (ZnEt2) furnishes a three-coordinated and mononuclear zinc complex [(AA(OMe))ZnEt] (2). Further reaction of 2 with a stoichiometric amount of benzyl alcohol (BnOH) affords a four-coordinated and dinuclear zinc benzylalkoxide complex [(AA(OMe))Zn(μ-OBn)]2 (3). In the presence of two equivalents of AA(OMe)-H with ZnEt2, a homoleptic and four-coordinated zinc complex [(AA(OMe))2Zn] (4) is formed. The geometry around the zinc centres of 3 and 4 are both distorted tetrahedrals, while 2 adopts a different coordination mode with a slightly distorted trigonal planar geometry. The variable-temperature (1)H NMR studies of 3 illustrate that 3 exhibits a dinuclear structure in solution at low temperature as well as in the solid state. While raising the temperature, it drifts towards dissociation to form a mononuclear zinc benzylalkoxide species, which coexists in solution. The ring-opening polymerizations of ε-caprolactone (ε-CL) and β-butyrolactone (β-BL) catalyzed by complexes 3 and 4 are investigated. The ε-CL and β-BL polymerizations initiated by zinc alkoxide 3 were demonstrated to have living characteristics and to proceed in a controlled manner with narrow polydispersity indices (PDIs high monomer-to-initiator ratio (1200/1) initiated by 3 has also been reported.

  15. Molecular docking of Glycine max and Medicago truncatula ureases with urea; bioinformatics approaches.

    Science.gov (United States)

    Filiz, Ertugrul; Vatansever, Recep; Ozyigit, Ibrahim Ilker

    2016-03-01

    Urease (EC 3.5.1.5) is a nickel-dependent metalloenzyme catalyzing the hydrolysis of urea into ammonia and carbon dioxide. It is present in many bacteria, fungi, yeasts and plants. Most species, with few exceptions, use nickel metalloenzyme urease to hydrolyze urea, which is one of the commonly used nitrogen fertilizer in plant growth thus its enzymatic hydrolysis possesses vital importance in agricultural practices. Considering the essentiality and importance of urea and urease activity in most plants, this study aimed to comparatively investigate the ureases of two important legume species such as Glycine max (soybean) and Medicago truncatula (barrel medic) from Fabaceae family. With additional plant species, primary and secondary structures of 37 plant ureases were comparatively analyzed using various bioinformatics tools. A structure based phylogeny was constructed using predicted 3D models of G. max and M. truncatula, whose crystallographic structures are not available, along with three additional solved urease structures from Canavalia ensiformis (PDB: 4GY7), Bacillus pasteurii (PDB: 4UBP) and Klebsiella aerogenes (PDB: 1FWJ). In addition, urease structures of these species were docked with urea to analyze the binding affinities, interacting amino acids and atom distances in urease-urea complexes. Furthermore, mutable amino acids which could potentially affect the protein active site, stability and flexibility as well as overall protein stability were analyzed in urease structures of G. max and M. truncatula. Plant ureases demonstrated similar physico-chemical properties with 833-878 amino acid residues and 89.39-90.91 kDa molecular weight with mainly acidic (5.15-6.10 pI) nature. Four protein domain structures such as urease gamma, urease beta, urease alpha and amidohydro 1 characterized the plant ureases. Secondary structure of plant ureases also demonstrated conserved protein architecture, with predominantly α-helix and random coil structures. In

  16. Multiple Identifications in Multi-Armed Bandits

    CERN Document Server

    Bubeck, Sébastien; Viswanathan, Nitin

    2012-01-01

    We study the problem of identifying the top $m$ arms in a multi-armed bandit game. Our proposed solution relies on a new algorithm based on successive rejects of the seemingly bad arms, and successive accepts of the good ones. This algorithmic contribution allows to tackle other multiple identifications settings that were previously out of reach. In particular we show that this idea of successive accepts and rejects applies to the multi-bandit best arm identification problem.

  17. Cloud and Star Formation in Spiral Arms

    CERN Document Server

    Dobbs, Clare

    2014-01-01

    We present the results from simulations of GMC formation in spiral galaxies. First we discuss cloud formation by cloud-cloud collisions, and gravitational instabilities, arguing that the former is prevalent at lower galactic surface densities and the latter at higher. Cloud masses are also limited by stellar feedback, which can be effective before clouds reach their maximum mass. We show other properties of clouds in simulations with different levels of feedback. With a moderate level of feedback, properties such as cloud rotations and virial parameters agree with observations. Without feedback, an unrealistic population of overly bound clouds develops. Spiral arms are not found to trigger star formation, they merely gather gas into more massive GMCs. We discuss in more detail interactions of clouds in the ISM, and argue that these are more complex than early ideas of cloud-cloud collisions. Finally we show ongoing work to determine whether the Milky Way is a flocculent or grand design spiral.

  18. Communications, tracking, and docking on the Space Station

    Science.gov (United States)

    Erwin, H. O.; Coden, M. H.; Scholl, F. W.

    1982-01-01

    Many of the communications, tracking, and docking functions on a large manned orbiting Space Station - one that is modular and made of metal - will have to be performed by optical systems out of necessity. This paper discusses four practical approaches to accomplishing Space Station functions using optical communications technology. It also provides the results of preliminary experiments involved in the design of particular systems. Major operational factors considered in each system design include: (a) electromagnetic interference problems, (b) data bandwidth requirements, (c) zero-gravity operations, (d) free-space operations, (e) data security, and (f) modular expansion of the Space Station structure. The technologies discussed are the following: (a) local infrared communications, (b) optical tracking and docking techniques, (c) long distance free space optical communications, and (d) local area optical networks.

  19. Docking Studies of Phthalimide Pharmacophore as a Sodium Channel Blocker

    Directory of Open Access Journals (Sweden)

    Maryam Iman

    2013-09-01

    Full Text Available   Objective(s: Recently, phthalimide derivatives were designed based on ameltolide and thalidomide as they possess a similar degree of anticonvulsant potency due to their phenytoin-like profile. The ability of phthalimide pharmacophore to interact with neuronal voltage-dependent sodium channels was studied in the batrachotoxin affinity assay. Therefore, in the present study, a series of 19 compounds of phthalimide pharmacophore possessing a variety of substituents (NO2, NH2 , Me, Cl, COOH, MeO at 2-, 3-, and 4- position of the N-phenyl ring and N-(3-amino-2-methylphenyl succinimide, were subjected to docking studies in order to inhibit voltage-gated sodium channels.   Materials and Methods : Chemical structures of all compounds were designed using HYPERCHEM program and Conformational studies were performed through semi-empirical molecular orbital calculations method followed by PM3 force field. Total energy gradient calculated as a root mean square (RMS value, until the RMS gradient was 0.01 kcal mol-1. Among all energy minima conformers, the global minimum of compounds was used in docking calculations. Using a model of the open pore of Na channels, docking study was performed by AUTODOCK4.2 program. Results : Docking studies have revealed that these types of ligands interacted mainly with II-S6 residues of NaV1.2 through making hydrogen bonds and have additional hydrophobic interactions with domain I, II, III and IV in the channel's inner pore. Conclusion   : These computational studies have displayed that these compounds are capable of inhibiting Na channel, efficiently.

  20. Genetic, Clinical, and Laboratory Markers for DOCK8 Immunodeficiency Syndrome

    Directory of Open Access Journals (Sweden)

    Jeremiah C. Davis

    2010-01-01

    Full Text Available DOCK8 immunodeficiency syndrome (DIDS is a combined immunodeficiency characterized by recurrent viral infections, severe atopy, and early onset malignancy. Genetic studies revealed large, unique deletions in patients from different families and ethnic backgrounds. Clinical markers of DIDS include atopic dermatitis, allergies, cutaneous viral infections, recurrent respiratory tract infections, and malignancy. Immune assessments showed T cell lymphopenia, hyper-IgE, hypo-IgM, and eosinophilia. The impaired lymphocyte functions in DIDS patients appear central for disease pathogenesis.

  1. In silico docking analysis of piperine with cyclooxygenases

    Directory of Open Access Journals (Sweden)

    Prashantha Karunakar

    2012-08-01

    Full Text Available The structure of 1-[5-(1,3-benzodioxol- 5-yl-1-oxo-2,4-pentadienyl]piperidine (Piperine, C17H19O3N, a versatile bioactive molecule has been redetermined at 100(2 K by X-raycrystallography to explore their potential utilization in inhibition of prostaglandin release. The crystal structure is stabilized by weaknonclassical intermolecular C-H…O hydrogen bonds and also intermolecular C-H…π interactions. The crystallographiccoordinates of the compound were extrapolated to docking studies to elucidate the action of piperine against the enzymes,cyclooxygenases (COX-1 and COX-2 involved in biosynthesis of prostaglandin release. Using AutoDock suite, piperine was docked at the binding site of COX-1 and COX-2 enzyme and a strong affinity (-9.06kcal/mol, Ki =227.73nM and -8.77kcal/mol, Ki = 375.62nM, respectively was formed by Hydrogen bonds and hydrophobic interactions. These results suggest that piperine can be a promising lead for the development of COX family inhibitors.

  2. Regenerator cross arm seal assembly

    Science.gov (United States)

    Jackman, Anthony V.

    1988-01-01

    A seal assembly for disposition between a cross arm on a gas turbine engine block and a regenerator disc, the seal assembly including a platform coextensive with the cross arm, a seal and wear layer sealingly and slidingly engaging the regenerator disc, a porous and compliant support layer between the platform and the seal and wear layer porous enough to permit flow of cooling air therethrough and compliant to accommodate relative thermal growth and distortion, a dike between the seal and wear layer and the platform for preventing cross flow through the support layer between engine exhaust and pressurized air passages, and air diversion passages for directing unregenerated pressurized air through the support layer to cool the seal and wear layer and then back into the flow of regenerated pressurized air.

  3. MODELING AND MOLECULAR DOCKING STUDIES ON ASPERGILLUS RNASE NIGER AND LEISHMANIA DONOVANI ACTIN: ANTILEISHMANIAL ACTIVITY

    Directory of Open Access Journals (Sweden)

    Ravi Kumar Gundampati

    2013-01-01

    Full Text Available A.niger Rnase was designed from ACTBIND (PDB ID: 3D3Z. Yeast actin-human gelsolin segment 1 complex (PDB ID: 1YAG was used as template for L. donovani actin protein for 3D model in Modeller9v8. These models were testified by PROCHECK, ERRAT, WHAT-IF, PROSA2003 and VERIFY-3D. All evidences suggest that the geometric quality of the backbone conformation, energy profile, residue interaction and contact of the structures were well within the limits of reliable structures. The interaction energy of docking was calculated using the HEX server. Etotal and calculated RMSD values were -1.902, -9.323 kcal moL-1 and 0.402 Å, respectively. The study presented here has an advantage to design molecules that may have antileishmanial activity.

  4. Molecular docking as a popular tool in drug design, an in silico travel.

    Science.gov (United States)

    de Ruyck, Jerome; Brysbaert, Guillaume; Blossey, Ralf; Lensink, Marc F

    2016-01-01

    New molecular modeling approaches, driven by rapidly improving computational platforms, have allowed many success stories for the use of computer-assisted drug design in the discovery of new mechanism-or structure-based drugs. In this overview, we highlight three aspects of the use of molecular docking. First, we discuss the combination of molecular and quantum mechanics to investigate an unusual enzymatic mechanism of a flavoprotein. Second, we present recent advances in anti-infectious agents' synthesis driven by structural insights. At the end, we focus on larger biological complexes made by protein-protein interactions and discuss their relevance in drug design. This review provides information on how these large systems, even in the presence of the solvent, can be investigated with the outlook of drug discovery.

  5. Robust Design of Docking Hoop for Recovery of Autonomous Underwater Vehicle with Experimental Results

    Directory of Open Access Journals (Sweden)

    Wei Peng Lin

    2015-12-01

    Full Text Available Control systems prototyping is usually constrained by model complexity, embedded system configurations, and interface testing. The proposed control system prototyping of a remotely-operated vehicle (ROV with a docking hoop (DH to recover an autonomous underwater vehicle (AUV named AUVDH using a combination of software tools allows the prototyping process to be unified. This process provides systematic design from mechanical, hydrodynamics, dynamics modelling, control system design, and simulation to testing in water. As shown in a three-dimensional simulation of an AUVDH model using MATLAB™/Simulink™ during the launch and recovery process, the control simulation of a sliding mode controller is able to control the positions and velocities under the external wave, current, and tether forces. In the water test using the proposed Python-based GUI platform, it shows that the AUVDH is capable to perform station-keeping under the external disturbances.

  6. Spectroscopic and Docking Studies on the Binding of Liquiritigenin with Hyaluronidase for Antiallergic Mechanism

    Directory of Open Access Journals (Sweden)

    Hua-jin Zeng

    2016-01-01

    Full Text Available The inhibitory effect of liquiritigenin on hyaluronidase and its binding mechanism were investigated systematically by UV-vis absorption, fluorescence, and molecular modeling approaches. These results indicated that liquiritigenin could interact with hyaluronidase to form a liquiritigenin-hyaluronidase complex. The binding constant, number of binding sites, and thermodynamic parameters were calculated, which indicated that liquiritigenin could spontaneously bind with hyaluronidase mainly through electrostatic and hydrophobic interactions with one binding site. Synchronous fluorescence, three-dimensional fluorescence, and molecular docking results revealed that liquiritigenin bound directly to the enzyme cavity site and this binding influenced the microenvironment of the hyaluronidase activity site, resulting in reduced hyaluronidase activity. The present study provides useful information for clinical applications of liquiritigenin as a hyaluronidase inhibitor.

  7. cis-Nitenpyram Analogues Containing 1,4-Dihydropyridine: Synthesis, Insecticidal Activities, and Molecular Docking Studies

    Institute of Scientific and Technical Information of China (English)

    孙传文; 陈艳霞; 刘天雁; 吴颖; 方庭; 王静; 邢家华

    2012-01-01

    A novel series of cb-nitenpyram analogues (2a--2p) were designed and prepared by introducing the 1,4-dihydropyridine, with their eis-configuration confirmed by X-ray diffraction. Preliminary bioassays showed that most compounds exhibited good insecticidal activities at 20 mg/L against Aphis medicagini, and analogues 2a and 2d aflbrded the best activity, and both of them had 100% mortality at 4 mg/L. In addition, molecular docking studies were also performed to model the ligand-receptor complexes, and the results explained the structure-activity relationships observed in vitro, which may provide some useful information for future design of new insecticides.

  8. Comparison of neural histomorphology in tail tips from pigs docked using clippers or cautery iron.

    Science.gov (United States)

    Kells, N J; Beausoleil, N J; Johnson, C B; Sutherland, M A; Morrison, R S; Roe, W

    2016-12-01

    Tail docking of pigs is commonly performed to reduce the incidence of unwanted tail-biting behaviour. Two docking methods are commonly used: blunt trauma cutting (i.e. using side clippers), or cutting and concurrent cauterisation using a hot cautery iron. A potential consequence of tail amputation is the development of neuromas at the docking site. Neuromas have been linked to neuropathic pain, which can influence the longer-term welfare of affected individuals. To determine whether method of tail docking influences the extent of neuroma formation, 75 pigs were allocated to one of three treatments at birth: tail docked using clippers; tail docked using cautery iron; tail left intact. Tail docking was performed at 2 days of age and pigs were kept under conventional conditions until slaughter at 21 weeks of age. Tails were removed following slaughter and subjected to histological examination. Nerve histomorphology was scored according to the following scale: 1=discrete well-organised nerve bundles; 2=moderate neural proliferation and disorganisation affecting more than half of the circumference of the tail; 3=marked neural proliferation to form almost continuous disorganised bundles or non-continuous enlarged bundles compressing the surrounding connective tissue. Scores of 2 or 3 indicated neuroma formation. Scores were higher in docked pigs than undocked pigs (Pclippers and those docked using cautery (P=0.23). The results indicate that tail docking using either clippers or cautery results in neuroma formation, thus having the potential to affect long-term pig welfare.

  9. Dual arm master controller concept

    Energy Technology Data Exchange (ETDEWEB)

    Kuban, D.P.; Perkins, G.S.

    1984-01-01

    The Advanced Servomanipulator (ASM) slave was designed with an anthropomorphic stance, gear/torque tube power drives, and modular construction. These features resulted in increased inertia, friction, and backlash relative to tape-driven manipulators. Studies were performed which addressed the human factors design and performance trade-offs associated with the corresponding master controller best suited for the ASM. The results of these studies, as well as the conceptual design of the dual arm master controller, are presented. 6 references, 3 figures.

  10. The DOE ARM Aerial Facility

    Energy Technology Data Exchange (ETDEWEB)

    Schmid, Beat; Tomlinson, Jason M.; Hubbe, John M.; Comstock, Jennifer M.; Mei, Fan; Chand, Duli; Pekour, Mikhail S.; Kluzek, Celine D.; Andrews, Elisabeth; Biraud, S.; McFarquhar, Greg

    2014-05-01

    The Department of Energy Atmospheric Radiation Measurement (ARM) Program is a climate research user facility operating stationary ground sites that provide long-term measurements of climate relevant properties, mobile ground- and ship-based facilities to conduct shorter field campaigns (6-12 months), and the ARM Aerial Facility (AAF). The airborne observations acquired by the AAF enhance the surface-based ARM measurements by providing high-resolution in-situ measurements for process understanding, retrieval-algorithm development, and model evaluation that are not possible using ground- or satellite-based techniques. Several ARM aerial efforts were consolidated into the AAF in 2006. With the exception of a small aircraft used for routine measurements of aerosols and carbon cycle gases, AAF at the time had no dedicated aircraft and only a small number of instruments at its disposal. In this "virtual hangar" mode, AAF successfully carried out several missions contracting with organizations and investigators who provided their research aircraft and instrumentation. In 2009, AAF started managing operations of the Battelle-owned Gulfstream I (G-1) large twin-turboprop research aircraft. Furthermore, the American Recovery and Reinvestment Act of 2009 provided funding for the procurement of over twenty new instruments to be used aboard the G-1 and other AAF virtual-hangar aircraft. AAF now executes missions in the virtual- and real-hangar mode producing freely available datasets for studying aerosol, cloud, and radiative processes in the atmosphere. AAF is also engaged in the maturation and testing of newly developed airborne sensors to help foster the next generation of airborne instruments.

  11. High precision detector robot arm system

    Science.gov (United States)

    Shu, Deming; Chu, Yong

    2017-01-31

    A method and high precision robot arm system are provided, for example, for X-ray nanodiffraction with an X-ray nanoprobe. The robot arm system includes duo-vertical-stages and a kinematic linkage system. A two-dimensional (2D) vertical plane ultra-precision robot arm supporting an X-ray detector provides positioning and manipulating of the X-ray detector. A vertical support for the 2D vertical plane robot arm includes spaced apart rails respectively engaging a first bearing structure and a second bearing structure carried by the 2D vertical plane robot arm.

  12. Scheduling trucks in cross docking systems with temporary storage and dock repeat truck holding pattern using GRASP method

    Directory of Open Access Journals (Sweden)

    Hassan Javanshir

    2012-10-01

    Full Text Available Cross docking play an important role in management of supply chains where items delivered to a warehouse by inbound trucks are directly sorted out, reorganized based on customer demands, routed and loaded into outbound trucks for delivery to customers without virtually keeping them at the warehouse. If any item is held in storage, it is usually for a short time, which is normally less than 24 hours. The proposed model of this paper considers a special case of cross docking where there is temporary storage and uses GRASP technique to solve the resulted problem for some realistic test problems. In our method, we first use some heuristics as initial solutions and then improve the final solution using GRASP method. The preliminary test results indicate that the GRASP method performs better than alternative solution strategies.

  13. Molecular Docking, Molecular Dynamics Simulations, Computational Screening to Design Quorum Sensing Inhibitors Targeting LuxP of Vibrio harveyi and Its Biological Evaluation.

    Science.gov (United States)

    Rajamanikandan, Sundaraj; Jeyakanthan, Jeyaraman; Srinivasan, Pappu

    2017-01-01

    Quorum sensing (QS) plays an important role in the biofilm formation, production of virulence factors and stress responses in Vibrio harveyi. Therefore, interrupting QS is a possible approach to modulate bacterial behavior. In the present study, three docking protocols, such as Rigid Receptor Docking (RRD), Induced Fit Docking (IFD), and Quantum Polarized Ligand Docking (QPLD) were used to elucidate the binding mode of boronic acid derivatives into the binding pocket of LuxP protein in V. harveyi. Among the three docking protocols, IFD accurately predicted the correct binding mode of the studied inhibitors. Molecular dynamics (MD) simulations of the protein-ligand complexes indicates that the inter-molecular hydrogen bonds formed between the protein and ligand complex remains stable during the simulation time. Pharmacophore and shape-based virtual screening were performed to find selective and potent compounds from ChemBridge database. Five hit compounds were selected and subjected to IFD and MD simulations to validate the binding mode. In addition, enrichment calculation was performed to discriminate and separate active compounds from the inactive compounds. Based on the computational studies, the potent Bicyclo [2.2.1] hept-5-ene-2,3-dicarboxylic acid-2,6-dimethylpyridine 1-oxide (ChemBridge_5144368) was selected for in vitro assays. The compound exhibited dose dependent inhibition in bioluminescence and also inhibits biofilm formation in V. harveyi to the level of 64.25 %. The result from the study suggests that ChemBridge_5144368 could serve as an anti-quorum sensing molecule for V. harveyi.

  14. Molecular modeling and docking simulations of scorpion toxins and related analogs on human SKCa2 and SKCa3 channels.

    Science.gov (United States)

    Andreotti, Nicolas; di Luccio, Eric; Sampieri, François; De Waard, Michel; Sabatier, Jean-Marc

    2005-07-01

    The small-conductance Ca2+-activated K+ (SKCa) channels modulate cytosolic Ca2+ concentration in excitable and non-excitable tissues by regulating the membrane potential and are responsible of slow action potential after hyperpolarization that inhibits cell firing. Among these, human SKCa2 and SKCa3 channels differ in the pore region by only two residues: Ala331 and Asn367 (human small-conductance calcium-activated potassium channel, hSKCa2) instead of Val485 and His521 (hSKCa3). To design highly selective blockers of hSKCa channels, a number of known hSKCa2 and/or hSKCa3-active peptides (i.e. scorpion toxins and analogs thereof) were analyzed for their interactions and selectivities toward these channels. Molecular models of hSKCa2 and hSKCa3 channels (S5-H5-S6 portion) were generated, and scorpion toxins/peptides of unsolved three-dimensional (3D) structures were modeled. Models of toxin-channel complexes were generated by the bimolecular complex generation with global evaluation, and ranking (BiGGER) docking software and selected by using a screening method of the docking solutions. A high degree of correlation was found to exist between docking energies and experimental Kd values of peptides that blocked hSKCa2 and/or hSKCa3 channels, suggesting it could be appropriate to predict Kd values of other bioactive peptides. The best scoring complexes were also used to identify key residues of both interacting partners, indicating that such an approach should help the design of more active and/or selective peptide blockers of targeted ion channels.

  15. Molecular modeling of methyl-α-Neu5Ac analogues docked against cholera toxin--a molecular dynamics study.

    Science.gov (United States)

    Blessy, J Jino; Sharmila, D Jeya Sundara

    2015-02-01

    Molecular modeling of synthetic methyl-α-Neu5Ac analogues modified in C-9 position was investigated by molecular docking and molecular dynamics (MD) simulation methods. Methyl-α-Neu5Ac analogues were docked against cholera toxin (CT) B subunit protein and MD simulations were carried out for three Methyl-α-Neu5Ac analogue-CT complexes (30, 10 and 10 ns) to estimate the binding activity of cholera toxin-Methyl-α-Neu5Ac analogues using OPLS_2005 force field. In this study, direct and water mediated hydrogen bonds play a vital role that exist between the methyl-α-9-N-benzoyl-amino-9-deoxy-Neu5Ac (BENZ)-cholera toxin active site residues. The Energy plot, RMSD and RMSF explain that the simulation was stable throughout the simulation run. Transition of phi, psi and omega angle for the complex was calculated. Molecular docking studies could be able to identify the binding mode of methyl-α-Neu5Ac analogues in the binding site of cholera toxin B subunit protein. MD simulation for Methyl-α-9-N-benzoyl-amino-9-deoxy-Neu5Ac (BENZ), Methyl-α-9-N-acetyl-9-deoxy-9-amino-Neu5Ac and Methyl-α-9-N-biphenyl-4-acetyl-deoxy-amino-Neu5Ac complex with CT B subunit protein was carried out, which explains the stable nature of interaction. These methyl-α-Neu5Ac analogues that have computationally acceptable pharmacological properties may be used as novel candidates for drug design for cholera disease.

  16. Ground Demonstration on the Autonomous Docking of Two 3U CubeSats Using a Novel Permanent-Magnet Docking Mechanism

    Science.gov (United States)

    Pei, Jing; Murchison, Luke; BenShabat, Adam; Stewart, Victor; Rosenthal, James; Follman, Jacob; Branchy, Mark; Sellers, Drew; Elandt, Ryan; Elliott, Sawyer; Choueiri, Marc; Finch, Peter

    2017-01-01

    Small spacecraft autonomous rendezvous and docking is an essential technology for future space structure assembly missions. A novel magnetic capture and latching mechanism is analyzed that allows for docking of two CubeSats without precise sensors and actuators. The proposed magnetic docking hardware not only provides the means to latch the CubeSats but it also significantly increases the likelihood of successful docking in the presence of relative attitude and position errors. The simplicity of the design allows it to be implemented on many CubeSat rendezvous missions. A CubeSat 3-DOF ground demonstration effort is on-going at NASA Langley Research Center that enables hardware-in-the loop testing of the autonomous approach and docking of a follower CubeSat to an identical leader CubeSat. The test setup consists of a 3 meter by 4 meter granite table and two nearly frictionless air bearing systems that support the two CubeSats. Four cold-gas on-off thrusters are used to translate the follower towards the leader, while a single reaction wheel is used to control the attitude of each CubeSat. An innovative modified pseudo inverse control allocation scheme was developed to address interactions between control effectors. The docking procedure requires relatively high actuator precision, a novel minimal impulse bit mitigation algorithm was developed to minimize the undesirable deadzone effects of the thrusters. Simulation of the ground demonstration shows that the Guidance, Navigation, and Control system along with the docking subsystem leads to successful docking under 3-sigma dispersions for all key system parameters. Extensive simulation and ground testing will provide sufficient confidence that the proposed docking mechanism along with the choosen suite of sensors and actuators will perform successful docking in the space environment.

  17. Evaluation of the effect of the chiral centers of Taxol on binding to β-tubulin: A docking and molecular dynamics simulation study.

    Science.gov (United States)

    Ghadari, Rahim; Alavi, Fatemeh S; Zahedi, Mansour

    2015-06-01

    Taxol is one of the most important anti-cancer drugs. The interaction between different variants of Taxol, by altering one of its chiral centers at a time, with β-tubulin protein has been investigated. To achieve such goal, docking and molecular dynamics (MD) simulation studies have been performed. In docking studies, the preferred conformers have been selected to further study by MD method based on the binding energies reported by the AutoDock program. The best result of docking study which shows the highest affinity between ligand and protein has been used as the starting point of the MD simulations. All of the complexes have shown acceptable stability during the simulation process, based on the RMSDs of the backbone of the protein structure. Finally, MM-GBSA calculations have been carried out to select the best ligand, considering the binding energy criteria. The results predict that two of the structures have better affinity toward the mentioned protein, in comparison with Taxol. Three of the structures have affinity similar to that of the Taxol toward the β-tubulin.

  18. Scheduling of Inbound Trucks at a Cross-Docking Facility: Bi-Objective VS Bi-Level Modeling Approaches

    OpenAIRE

    Golias, Mihalis M.; Saharidis, Georgios K.D.; Maria Boile; Sotirios Theofanis

    2012-01-01

    This paper examines the problem of scheduling of inbound trucks to the inbound doors at a cross-docking facility. The authors optimize for two conflicting objectives: minimize the total service time for all the inbound trucks and minimize the delayed completion of service for a subset of the inbound trucks, which are considered as preferential customers. The problem is formulated as a bi-objective and as a bi-level mixed integer problem. Due to the nature of the former and the complexity of t...

  19. In Pursuit of Fully Flexible Protein-Ligand Docking: Modeling the Bilateral Mechanism of Binding.

    Science.gov (United States)

    Henzler, Angela M; Rarey, Matthias

    2010-03-15

    Modern structure-based drug design aims at accounting for the intrinsic flexibility of therapeutic relevant targets. Over the last few years a considerable amount of docking approaches that encounter this challenging problem has emerged. Here we provide the readership with an overview of established methods for fully flexible protein-ligand docking and current developments in the field. All methods are based on one of two fundamental models which describe the dynamic behavior of proteins upon ligand binding. Methods for ensemble docking (ED) model the protein conformational change before the ligand is placed, whereas induced-fit docking (IFD) optimizes the protein structure afterwards. A third category of docking approaches is formed by recent approaches that follow both concepts. This categorization allows to comprehensively discover strengths and weaknesses of the individual processes and to extract information for their applicability in real world docking scenarios.

  20. Molecular docking for thrombolytic activity of some isolated compounds from Clausena lansium.

    Directory of Open Access Journals (Sweden)

    Arkajyoti Paul

    2017-03-01

    Full Text Available Clausena lansium (Family- Rutaceae is commonly known as wampee, is found in fallow lands throughout Bangladesh. Our aim of the study to performed molecular docking studies to identify potential binding affinities of the phytocompounds from Clausena lansium, namely Clausemarin B, Clausenaline C, Clausenaline E, Murrayanine, vanillic acid and Xanthotoxol for searching of lead molecule for thrombolytic activity. A wide range of docking score found during molecular docking by Schrodinger. Clausemarin B , Clausenaline C , Clausenaline E, Murrayanine , vanillic acid and Xanthotoxol showed the docking score -6.926, -4.041, -4.889 , -4.356, -3.007 and -5.816 respectively. Among all the compounds Clausemarin B showed the best docking score. So, Clausemarin B is the best compounds for thrombolytic activity, as it possessed the best value in Molecular docking. Further in vivo investigation need to identify the thrombolytic activity of isolated compounds from Clausena lansium.

  1. ASTP crewmen in Docking Module trainer during training session at JSC

    Science.gov (United States)

    1975-01-01

    An interior view of the Docking Module trainer in bldg 35 during Apollo Soyuz Test Project (ASTP) joint crew training at JSC. Astronaut Donald K. Slayton (right) is the docking module pilot of the American ASTP prime crew. The other man is Cosmonaut Valeriy N. Kubasov, engineer on the Soviet ASTP first (prime) crew. The training session simulated activities on the second day in space. The Docking module is designed to link the Apollo and Soyuz spacecraft.

  2. Hypomorphic function and somatic reversion of DOCK8 cause combined immunodeficiency without hyper-IgE.

    Science.gov (United States)

    Kienzler, Anne-Kathrin; van Schouwenburg, Pauline A; Taylor, John; Marwah, Ishita; Sharma, Richa U; Noakes, Charlotte; Thomson, Kate; Sadler, Ross; Segal, Shelley; Ferry, Berne; Taylor, Jenny C; Blair, Edward; Chapel, Helen; Patel, Smita Y

    2016-02-01

    Loss-of-function mutations in DOCK8 are linked to hyper-IgE syndrome. Patients typically present with recurrent sinopulmonary infections, severe cutaneous viral infections, food allergies and elevated serum IgE. Although patients may present with a spectrum of disease-related symptoms, molecular mechanisms explaining phenotypic variability in patients are poorly defined. Here we characterized a novel compound heterozygous mutation in DOCK8 in a patient diagnosed with primary combined immunodeficiency which was not typical of classical DOCK8 deficiency. In contrast to previously identified mutations in DOCK8 which result in complete loss of function, the newly identified single nucleotide insertion results in expression of a truncated DOCK8 protein. Functional evaluation of the truncated DOCK8 protein revealed its hypomorphic function. In addition we found somatic reversion of DOCK8 predominantly in T cells. The combination of somatic reversion and hypomorphic DOCK8 function explains the milder and atypical phenotype of the patient and further broadens the spectrum of DOCK8-associated disease.

  3. SPACECRAFT DOCKING SIMULATION USING HARDWARE-IN-THE-LOOP SIMULATOR WITH STEWART PLATFORM

    Institute of Scientific and Technical Information of China (English)

    Huang Qitao; Jiang Hongzhou; Zhang Shangying; Han Junwei

    2005-01-01

    A ground-based hardware-in-the-loop (HIL) simulation system with hydraulically driven Stewart platform for spacecraft docking simulation is presented. The system is used for simulating docking process of the on-orbit spacecraft. Principle and structure of the six-degree-of-freedom simulation system are introduced. The docking process dynamic of the vehicles is modeled. Experiment results and mathematical simulation data are compared to validating the simulation system. The comparisons of the results prove that the simulation system proposed can effectively simulate the on-orbit docking process of the spacecraft.

  4. Ligand-protein docking: cancer research at the interface between biology and chemistry.

    Science.gov (United States)

    Glen, R C; Allen, S C

    2003-05-01

    years. For example, some methods rely on complex molecular dynamics simulations while others use less costly graph matching approaches. There is generally a compromise between speed and accuracy, with some methods giving much more information and insight into the nature of the protein/ligand interactions and other methods optimised for speed of docking thousands of putative ligands. We will describe some of the more common methods and algorithms used to solve the docking problem and in particular, we will review recent applications in cancer research.

  5. Dual arm master controller development

    Energy Technology Data Exchange (ETDEWEB)

    Kuban, D.P.; Perkins, G.S.

    1985-01-01

    The advanced servomanipulator (ASM) slave was designed with an anthropomorphic stance, gear/torque tube power drives, and modular construction. These features resulted in increased inertia, friction, and backlash relative to tape-driven manipulators. Studies were performed which addressed the human factors design and performance trade-offs associated with the corresponding master controller best suited for the ASM. The results of these studies, as well as the conceptual design of the dual arm master controller, are presented. This work was performed as part of the Consolidated Fuel Reprocessing Program at the Oak Ridge National Laboratory. 5 refs., 7 figs., 1 tab.

  6. Arms Race in Maghreb Region

    Institute of Scientific and Technical Information of China (English)

    EL AMOURI ALLAL

    2016-01-01

    Maghreb countries competitive altitude towards each other’ s has reached a higher level by entering an arms race.Morocco and Al ̄geria have dominated more than 50 percent of the Africa’ s imported weapons,mainly because of inherited cold war mentality of competi ̄tion and hostility. Maghreb countries competition has drugged the re ̄gion into a chaos that threatens regional stability obviously which af ̄fect the domestic political stability,since military spending weakens the financial capacity of states.

  7. Developing a Comparative Docking Protocol for the Prediction of Peptide Selectivity Profiles: Investigation of Potassium Channel Toxins

    Directory of Open Access Journals (Sweden)

    Serdar Kuyucak

    2012-02-01

    Full Text Available During the development of selective peptides against highly homologous targets, a reliable tool is sought that can predict information on both mechanisms of binding and relative affinities. These tools must first be tested on known profiles before application on novel therapeutic candidates. We therefore present a comparative docking protocol in HADDOCK using critical motifs, and use it to “predict” the various selectivity profiles of several major αKTX scorpion toxin families versus Kv1.1, Kv1.2 and Kv1.3. By correlating results across toxins of similar profiles, a comprehensive set of functional residues can be identified. Reasonable models of channel-toxin interactions can be then drawn that are consistent with known affinity and mutagenesis. Without biological information on the interaction, HADDOCK reproduces mechanisms underlying the universal binding of αKTX-2 toxins, and Kv1.3 selectivity of αKTX-3 toxins. The addition of constraints encouraging the critical lysine insertion confirms these findings, and gives analogous explanations for other families, including models of partial pore-block in αKTX-6. While qualitatively informative, the HADDOCK scoring function is not yet sufficient for accurate affinity-ranking. False minima in low-affinity complexes often resemble true binding in high-affinity complexes, despite steric/conformational penalties apparent from visual inspection. This contamination significantly complicates energetic analysis, although it is usually possible to obtain correct ranking via careful interpretation of binding-well characteristics and elimination of false positives. Aside from adaptations to the broader potassium channel family, we suggest that this strategy of comparative docking can be extended to other channels of interest with known structure, especially in cases where a critical motif exists to improve docking effectiveness.

  8. A Geometric Approach for Robotic Arm Kinematics with Hardware Design, Electrical Design, and Implementation

    Directory of Open Access Journals (Sweden)

    Kurt E. Clothier

    2010-01-01

    Full Text Available This paper presents a geometric approach to solve the unknown joint angles required for the autonomous positioning of a robotic arm. A plethora of complex mathematical processes is reduced using basic trigonometric in the modeling of the robotic arm. This modeling and analysis approach is tested using a five-degree-of-freedom arm with a gripper style end effector mounted to an iRobot Create mobile platform. The geometric method is easily modifiable for similar robotic system architectures and provides the capability of local autonomy to a system which is very difficult to manually control.

  9. Anthropometric considerations for a 4-axis side-arm flight controller

    Science.gov (United States)

    Debellis, W. B.

    1986-01-01

    A data base on multiaxis side-arm flight controls was generated. The rapid advances in fly-by-light technology, automatic stability systems, and onboard computers have combined to create flexible flight control systems which could reduce the workload imposed on the operator by complex new equipment. This side-arm flight controller combines four controls into one unit and should simplify the pilot's task. However, the use of a multiaxis side-arm flight controller without complete cockpit integration may tend to increase the pilot's workload.

  10. Ligand pose and orientational sampling in molecular docking.

    Directory of Open Access Journals (Sweden)

    Ryan G Coleman

    Full Text Available Molecular docking remains an important tool for structure-based screening to find new ligands and chemical probes. As docking ambitions grow to include new scoring function terms, and to address ever more targets, the reliability and extendability of the orientation sampling, and the throughput of the method, become pressing. Here we explore sampling techniques that eliminate stochastic behavior in DOCK3.6, allowing us to optimize the method for regularly variable sampling of orientations. This also enabled a focused effort to optimize the code for efficiency, with a three-fold increase in the speed of the program. This, in turn, facilitated extensive testing of the method on the 102 targets, 22,805 ligands and 1,411,214 decoys of the Directory of Useful Decoys-Enhanced (DUD-E benchmarking set, at multiple levels of sampling. Encouragingly, we observe that as sampling increases from 50 to 500 to 2000 to 5000 to 20,000 molecular orientations in the binding site (and so from about 1×10(10 to 4×10(10 to 1×10(11 to 2×10(11 to 5×10(11 mean atoms scored per target, since multiple conformations are sampled per orientation, the enrichment of ligands over decoys monotonically increases for most DUD-E targets. Meanwhile, including internal electrostatics in the evaluation ligand conformational energies, and restricting aromatic hydroxyls to low energy rotamers, further improved enrichment values. Several of the strategies used here to improve the efficiency of the code are broadly applicable in the field.

  11. Binding between Saikosaponin C and Human Serum Albumin by Fluorescence Spectroscopy and Molecular Docking

    Directory of Open Access Journals (Sweden)

    Yi-Cun Chen

    2016-01-01

    Full Text Available Saikosaponin C (SSC is one of the major active constituents of dried Radix bupleuri root (Chaihu in Chinese that has been widely used in China to treat a variety of conditions, such as liver disease, for many centuries. The binding of SSC to human serum albumin (HSA was explored by fluorescence, circular dichroism (CD, UV-vis spectrophotometry, and molecular docking to understand both the pharmacology and the basis of the clinical use of SSC/Chaihu. SSC produced a concentration-dependent quenching effect on the intrinsic fluorescence of HSA, accompanied by a blue shift in the fluorescence spectra. The Stern-Volmer equation showed that this quenching was dominated by static quenching. The binding constant of SSC with HSA was 3.72 × 103 and 2.99 × 103 L·mol−1 at 26 °C and 36 °C, respectively, with a single binding site on each SSC and HSA molecule. Site competitive experiments demonstrated that SSC bound to site I (subdomain IIA and site II (subdomain IIIA in HSA. Analysis of thermodynamic parameters indicated that hydrogen bonding and van der Waals forces were mostly responsible for SSC-HSA association. The energy transfer efficiency and binding distance between SSC and HSA was calculated to be 0.23 J and 2.61 nm at 26 °C, respectively. Synchronous fluorescence and CD measurements indicated that SSC affected HSA conformation in the SSC-HSA complex. Molecular docking supported the experimental findings in conformational changes, binding sites and binding forces, and revealed binding of SSC at the interface between subdomains IIA-IIB.

  12. Docking study of HIV-1 reverse transcriptase with phytochemicals.

    Science.gov (United States)

    Seal, Abhik; Aykkal, Riju; Babu, Rosana O; Ghosh, Mriganka

    2011-02-15

    Natural products are important sources of drug discovery. In this context groups of different set of phytochemicals were taken and docked into the different cavities of the Reverse transcriptase (PDB ID: 1REV) of Human immunodeficiency virus (HIV) and results were discussed. Natural compounds such as Curcumin, Geranin, Gallotannin, Tiliroside, Kaempferol-3-o-glucoside and Trachelogenin were found to very effective according to its binding energy and ligand efficiency score. Those compounds also were found to have no adverse effect as carcinogenicity and mutagenicity and favorable drug likeness score. Hence, considering the facts those compounds could use effectively for HIV-1 drug discovery.

  13. APOLLO 14: Docking trouble (pt 1/2)

    Science.gov (United States)

    1974-01-01

    APOLLO 14: The crew are having problems docking the command module to the lunar module: the locking mechanism will not engage. From the film documentary 'APOLLO 14: 'Mission to Fra Mauro'', part of a documentary series on the APOLLO missions made in the early '70's and narrated by Burgess Meredith. APOLO 14: Third manned lunar landing with Alan B. Shepard, Jr.,Stuart A. Roosa, and Edgar D. Mitchell. Landed in the Fra Mauro area on Ferurary 5, 1971; performed EVA, deployed lunar experiments, returned lunar samples. Mission Duration 216 hrs 1 min 58 sec

  14. StarDock: shipping customized computing environments to the data

    Science.gov (United States)

    Young, Michael D.; Hayashi, Soichi; Gopu, Arvind

    2016-08-01

    Surging data volumes make it increasingly unfeasible to transfer astronomical datasets to the local systems of individual scientists. Centralized pipelines offer some relief, but lack flexibility to fulfill the needs of all users. We have developed a system that leverages the Docker container application virtualization software. Along with a suite of commonly used astronomy applications, users can configure a container with their own custom software and analysis tools. Our StarDock system will move the users container to the data, and expose the requested dataset, allowing our users to safely and securely process their data without needlessly transferring hundreds of gigabytes.

  15. Synthesis, antiproliferative activity and molecular docking of Colchicine derivatives.

    Science.gov (United States)

    Huczyński, Adam; Majcher, Urszula; Maj, Ewa; Wietrzyk, Joanna; Janczak, Jan; Moshari, Mahshad; Tuszynski, Jack A; Bartl, Franz

    2016-02-01

    In order to create more potent anticancer agents, a series of five structurally different derivatives of Colchicine have been synthesised. These compounds were characterised spectroscopically and structurally and their antiproliferative activity against four human tumour cell lines (HL-60, HL-60/vinc, LoVo, LoVo/DX) was evaluated. Additionally the activity of the studied compounds was calculated using computational methods involving molecular docking of the Colchicine derivatives to β-tubulin. The experimental and computational results are in very good agreement indicating that the antimitotic activity of Colchicine derivatives can be readily predicted using computational modeling methods.

  16. SYNTHESIS, DOCKING STUDIES AND ANTIOXIDANT ACTIVITY OF LINEAR TETRAPEPTIDE FAYV

    Directory of Open Access Journals (Sweden)

    Sreekanth K.

    2011-07-01

    Full Text Available The linear tetrapeptide Phe-Ala-Tyr-Val (FAYV was designed based on docking results using Schrodinger Software tool. The tetrapeptide was conveniently synthesized by solution phase peptide synthesis using Dicyclohexylcarbidomide (DCC as coupling agent and triethyl amine as the base. Qikprop (a tool to predict drug like properties results showed that the ligands mostly show antihypertensive and antidiabetic properties. The compounds were evaluated for antioxidant property by using 1,1-diphenyl-2-picryl-hydrazil (DPPH. method and were found to possess significant antioxidant activity.

  17. Bio-inspired algorithms applied to molecular docking simulations.

    Science.gov (United States)

    Heberlé, G; de Azevedo, W F

    2011-01-01

    Nature as a source of inspiration has been shown to have a great beneficial impact on the development of new computational methodologies. In this scenario, analyses of the interactions between a protein target and a ligand can be simulated by biologically inspired algorithms (BIAs). These algorithms mimic biological systems to create new paradigms for computation, such as neural networks, evolutionary computing, and swarm intelligence. This review provides a description of the main concepts behind BIAs applied to molecular docking simulations. Special attention is devoted to evolutionary algorithms, guided-directed evolutionary algorithms, and Lamarckian genetic algorithms. Recent applications of these methodologies to protein targets identified in the Mycobacterium tuberculosis genome are described.

  18. Latent herpesvirus infection arms NK cells.

    Science.gov (United States)

    White, Douglas W; Keppel, Catherine R; Schneider, Stephanie E; Reese, Tiffany A; Coder, James; Payton, Jacqueline E; Ley, Timothy J; Virgin, Herbert W; Fehniger, Todd A

    2010-06-03

    Natural killer (NK) cells were identified by their ability to kill target cells without previous sensitization. However, without an antecedent "arming" event, NK cells can recognize, but are not equipped to kill, target cells. How NK cells become armed in vivo in healthy hosts is unclear. Because latent herpesviruses are highly prevalent and alter multiple aspects of host immunity, we hypothesized that latent herpesvirus infection would arm NK cells. Here we show that NK cells from mice latently infected with Murid herpesvirus 4 (MuHV-4) were armed as evidenced by increased granzyme B protein expression, cytotoxicity, and interferon-gamma production. NK-cell arming occurred rapidly in the latently infected host and did not require acute viral infection. Furthermore, NK cells armed by latent infection protected the host against a lethal lymphoma challenge. Thus, the immune environment created by latent herpesvirus infection provides a mechanism whereby host NK-cell function is enhanced in vivo.

  19. Application of C-arm computed tomography in cardiology; Kardiale Anwendung der C-Arm-Computertomographie

    Energy Technology Data Exchange (ETDEWEB)

    Rieber, J. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Innenstadt, Abteilung fuer Kardiologie, Medizinische Poliklinik, Muenchen (Germany); Rohkohl, C. [Friedrich-Alexander-Universitaet Erlangen-Nuernberg, Lehrstuhl fuer Mustererkennung, Department Informatik, Erlangen (Germany); Siemens AG, Healthcare Sector, Forchheim, Forchheim (Germany); Lauritsch, G. [Siemens AG, Healthcare Sector, Forchheim, Forchheim (Germany); Rittger, H. [Krankenhaus Coburg, Abteilung fuer Kardiologie, Coburg (Germany); Meissner, O. [Siemens AG, Healthcare Sector, Forchheim, Forchheim (Germany); Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Institut fuer Klinische Radiologie, Muenchen (Germany)

    2009-09-15

    C-arm computed tomography is currently being introduced into cardiac imaging and offers the potential for three-dimensional imaging of the cardiac anatomy within the interventional environment. This detailed view is necessary to support complex interventional strategies, such as transcutaneous valve replacement, interventional therapy of atrial fibrillation, implantation of biventricular pacemakers and assessment of myocardial perfusion. Currently, the major limitation of this technology is its insufficient temporal resolution which limits the visualization of fast moving parts of the heart. (orig.) [German] Durch die Entwicklung der C-Arm-Computertomographie- (CACT-)Angiographie ist es erstmals moeglich, waehrend einer Herzkatheteruntersuchung eine detaillierte dreidimensionale Darstellung der kardialen Anatomie zu erhalten. Derartige zusaetzliche Informationen koennten die Durchfuehrung der immer komplexer werdenden Strategien der interventionellen Kardiologie wirkungsvoll unterstuetzen. Hierzu zaehlen u. a. der transkutane Klappenersatz, die interventionelle Behandlung von Vorhofflimmern, die Implantation biventrikulaerer Schrittmacher sowie die Beurteilung der Myokardperfusion. Die derzeit groesste Limitation dieser Methode ist die relativ geringe zeitliche Aufloesung, die aufgrund der Bewegung des Herzens die Anwendung dieser Technologie einschraenkt. (orig.)

  20. Coordinated Resolved Motion Control of Dual-arm Manipulators with Closed Chain

    OpenAIRE

    Tianliang Liu; Yan Lei; Liang Han; Wenfu Xu; Huaiwu Zou

    2016-01-01

    When applied to some tasks, such as payload handling, assembling, repairing and so on, the two arms of a humanoid robot will form a closed kinematic chain. It makes the motion planning and control for dual‐arm coordination very complex and difficult. In this paper, we present three types of resolved motion control methods for a humanoid robot during coordinated manipulation. They are, respectively, position‐level, velocity‐level and acceleration‐level resolved motion control methods. The desi...

  1. Protein-ligand docking using hamiltonian replica exchange simulations with soft core potentials.

    Science.gov (United States)

    Luitz, Manuel P; Zacharias, Martin

    2014-06-23

    Molecular dynamics (MD) simulations in explicit solvent allow studying receptor-ligand binding processes including full flexibility of the binding partners and an explicit inclusion of solvation effects. However, in MD simulations, the search for an optimal ligand-receptor complex geometry is frequently trapped in locally stable non-native binding geometries. A Hamiltonian replica-exchange (H-REMD)-based protocol has been designed to enhance the sampling of putative ligand-receptor complexes. It is based on softening nonbonded ligand-receptor interactions along the replicas and one reference replica under the control of the original force field. The efficiency of the method has been evaluated on two receptor-ligand systems and one protein-peptide complex. Starting from misplaced initial docking geometries, the H-REMD method reached in each case the known binding geometry significantly faster than a standard MD simulation. The approach could also be useful to identify and evaluate alternative binding geometries in a given binding region with small relative differences in binding free energy.

  2. Atmospheric Radiation Measurement Climate Research (ARM)

    Data.gov (United States)

    Federal Laboratory Consortium — With heavily instrumented field sites around the globe, the ARM Climate Research Facility provides the world's most comprehensive outdoor laboratory and data archive...

  3. An Automated Strategy for Binding-Pose Selection and Docking Assessment in Structure-Based Drug Design.

    Science.gov (United States)

    Ballante, Flavio; Marshall, Garland R

    2016-01-25

    Molecular docking is a widely used technique in drug design to predict the binding pose of a candidate compound in a defined therapeutic target. Numerous docking protocols are available, each characterized by different search methods and scoring functions, thus providing variable predictive capability on a same ligand-protein system. To validate a docking protocol, it is necessary to determine a priori the ability to reproduce the experimental binding pose (i.e., by determining the docking accuracy (DA)) in order to select the most appropriate docking procedure and thus estimate the rate of success in docking novel compounds. As common docking programs use generally different root-mean-square deviation (RMSD) formulas, scoring functions, and format results, it is both difficult and time-consuming to consistently determine and compare their predictive capabilities in order to identify the best protocol to use for the target of interest and to extrapolate the binding poses (i.e., best-docked (BD), best-cluster (BC), and best-fit (BF) poses) when applying a given docking program over thousands/millions of molecules during virtual screening. To reduce this difficulty, two new procedures called Clusterizer and DockAccessor have been developed and implemented for use with some common and "free-for-academics" programs such as AutoDock4, AutoDock4(Zn), AutoDock Vina, DOCK, MpSDockZn, PLANTS, and Surflex-Dock to automatically extrapolate BD, BC, and BF poses as well as to perform consistent cluster and DA analyses. Clusterizer and DockAccessor (code available over the Internet) represent two novel tools to collect computationally determined poses and detect the most predictive docking approach. Herein an application to human lysine deacetylase (hKDAC) inhibitors is illustrated.

  4. Cortical Spiking Network Interfaced with Virtual Musculoskeletal Arm and Robotic Arm.

    Science.gov (United States)

    Dura-Bernal, Salvador; Zhou, Xianlian; Neymotin, Samuel A; Przekwas, Andrzej; Francis, Joseph T; Lytton, William W

    2015-01-01

    Embedding computational models in the physical world is a critical step towards constraining their behavior and building practical applications. Here we aim to drive a realistic musculoskeletal arm model using a biomimetic cortical spiking model, and make a robot arm reproduce the same trajectories in real time. Our cortical model consisted of a 3-layered cortex, composed of several hundred spiking model-neurons, which display physiologically realistic dynamics. We interconnected the cortical model to a two-joint musculoskeletal model of a human arm, with realistic anatomical and biomechanical properties. The virtual arm received muscle excitations from the neuronal model, and fed back proprioceptive information, forming a closed-loop system. The cortical model was trained using spike timing-dependent reinforcement learning to drive the virtual arm in a 2D reaching task. Limb position was used to simultaneously control a robot arm using an improved network interface. Virtual arm muscle activations responded to motoneuron firing rates, with virtual arm muscles lengths encoded via population coding in the proprioceptive population. After training, the virtual arm performed reaching movements which were smoother and more realistic than those obtained using a simplistic arm model. This system provided access to both spiking network properties and to arm biophysical properties, including muscle forces. The use of a musculoskeletal virtual arm and the improved control system allowed the robot arm to perform movements which were smoother than those reported in our previous paper using a simplistic arm. This work provides a novel approach consisting of bidirectionally connecting a cortical model to a realistic virtual arm, and using the system output to drive a robotic arm in real time. Our techniques are applicable to the future development of brain neuroprosthetic control systems, and may enable enhanced brain-machine interfaces with the possibility for finer control of

  5. Cortical spiking network interfaced with virtual musculoskeletal arm and robotic arm

    Directory of Open Access Journals (Sweden)

    Salvador eDura-Bernal

    2015-11-01

    Full Text Available Embedding computational models in the physical world is a critical step towards constraining their behavior and building practical applications. Here we aim to drive a realistic musculoskeletal arm model using a biomimetic cortical spiking model, and make a robot arm reproduce the same trajectories in real time. Our cortical model consisted of a 3-layered cortex, composed of several hundred spiking model-neurons, which display physiologically realistic dynamics. We interconnected the cortical model to a two-joint musculoskeletal model of a human arm, with realistic anatomical and biomechanical properties. The virtual arm received muscle excitations from the neuronal model, and fed back proprioceptive information, forming a closed-loop system. The cortical model was trained using spike timing-dependent reinforcement learning to drive the virtual arm in a 2D reaching task. Limb position was used to simultaneously control a robot arm using an improved network interface. Virtual arm muscle activations responded to motoneuron firing rates, with virtual arm muscles lengths encoded via population coding in the proprioceptive population. After training, the virtual arm performed reaching movements which were smoother and more realistic than those obtained using a simplistic arm model. This system provided access to both spiking network properties and to arm biophysical properties, including muscle forces. The use of a musculoskeletal virtual arm and the improved control system allowed the robot arm to perform movements which were smoother than those reported in our previous paper using a simplistic arm.This work provides a novel approach consisting of bidirectionally connecting a cortical model to a realistic virtual arm, and using the system output to drive a robotic arm in real time. Our techniques are applicable to the future development of brain neuro-prosthetic control systems, and may enable enhanced brain-machine interfaces with the possibility

  6. Docks and Piers, Port of Green Bay docks along the Fox River are complete, Published in 2008, 1:1200 (1in=100ft) scale, Brown County, WI.

    Data.gov (United States)

    NSGIC GIS Inventory (aka Ramona) — This Docks and Piers dataset, published at 1:1200 (1in=100ft) scale, was produced all or in part from Orthoimagery information as of 2008. It is described as 'Port...

  7. Connecting in Space: Docking with the International Space Station. Educational Brief.

    Science.gov (United States)

    National Aeronautics and Space Administration, Washington, DC.

    This brief discusses the space shuttle and the docking procedures used with the International Space Station (ISS). Using this activity designed for grades 5-12, students demonstrate and identify procedures for determining the best method for completing the docking activity. Students will also study and identify Newton's Laws of Motion. A mockup…

  8. Molecular mechanism of serotonin transporter inhibition elucidated by a new flexible docking protocol.

    Science.gov (United States)

    Gabrielsen, Mari; Kurczab, Rafał; Ravna, Aina W; Kufareva, Irina; Abagyan, Ruben; Chilmonczyk, Zdzisław; Bojarski, Andrzej J; Sylte, Ingebrigt

    2012-01-01

    The two main groups of antidepressant drugs, the tricyclic antidepressants (TCAs) and the selective serotonin reuptake inhibitors (SSRIs), as well as several other compounds, act by inhibiting the serotonin transporter (SERT). However, the binding mode and molecular mechanism of inhibition in SERT are not fully understood. In this study, five classes of SERT inhibitors were docked into an outward-facing SERT homology model using a new 4D ensemble docking protocol. Unlike other docking protocols, where protein flexibility is not considered or is highly dependent on the ligand structure, flexibility was here obtained by side chain sampling of the amino acids of the binding pocket using biased probability Monte Carlo (BPMC) prior to docking. This resulted in the generation of multiple binding pocket conformations that the ligands were docked into. The docking results showed that the inhibitors were stacked between the aromatic amino acids of the extracellular gate (Y176, F335) presumably preventing its closure. The inhibitors interacted with amino acids in both the putative substrate binding site and more extracellular regions of the protein. A general structure-docking-based pharmacophore model was generated to explain binding of all studied classes of SERT inhibitors. Docking of a test set of actives and decoys furthermore showed that the outward-facing ensemble SERT homology model consistently and selectively scored the majority of active compounds above decoys, which indicates its usefulness in virtual screening.

  9. 48 CFR 52.247-40 - Ex Dock, Pier, or Warehouse, Port of Importation.

    Science.gov (United States)

    2010-10-01

    ... Warehouse, Port of Importation. 52.247-40 Section 52.247-40 Federal Acquisition Regulations System FEDERAL... Provisions and Clauses 52.247-40 Ex Dock, Pier, or Warehouse, Port of Importation. As prescribed in 47.303-12..., pier, or warehouse, port of importation: Ex Dock, Pier, or Warehouse, Port of Importation (APR 1984)...

  10. 75 FR 38831 - Repair Kalaupapa Dock Structure: Kalaupapa National Historical Park, Hawaii; Notice of...

    Science.gov (United States)

    2010-07-06

    ... National Park Service Repair Kalaupapa Dock Structure: Kalaupapa National Historical Park, Hawaii; Notice... Impact Statement (EIS) as previously noticed in the Federal Register on April 17, 2009, for repair of... environmental consequences of the proposed dock repairs, including minor to moderate effects on water...

  11. Economic Impacts from Spending by Community Dock Owners at Rough River Lake

    Science.gov (United States)

    2008-01-01

    community dock • Pomme de Terre Lake, community dock • Harry S. Truman Dam and Reservoir, marina • Raystown Lake, marina • Hartwell Lake, private...Rock Lake (Missouri/Arkansas), Rough River Lake (Kentucky), and Pomme de Terre Lake (Missouri). The ERB staff designed the survey, constructed the

  12. Attitudes of Dutch Pig Farmers Towards Tail Biting and Tail Docking

    NARCIS (Netherlands)

    Bracke, M.B.M.; Lauwere, de C.C.; Wind, S.M.M.; Zonderland, J.J.

    2013-01-01

    The Dutch policy objective of a fully sustainable livestock sector without mutilations by 2023 is not compatible with the routine practice of tail docking to minimize the risk of tail biting. To examine farmer attitudes towards docking, a telephone survey was conducted among 487 conventional and 33

  13. DOCK8 Deficiency : Clinical and Immunological Phenotype and Treatment Options - a Review of 136 Patients

    NARCIS (Netherlands)

    Aydin, Susanne E.; Kilic, Sara Sebnem; Aytekin, Caner; Kumar, Ashish; Porras, Oscar; Kainulainen, Leena; Kostyuchenko, Larysa; Genel, Ferah; Kutukculer, Necil; Karaca, Neslihan; Gonzalez-Granado, Luis; Abbott, Jordan; Al-Zahrani, Daifulah; Rezaei, Nima; Baz, Zeina; Thiel, Jens; Ehl, Stephan; Marodi, Laszlo; Orange, Jordan S.; Sawalle-Belohradsky, Julie; Keles, Sevgi; Holland, Steven M.; Sanal, Ozden; Ayvaz, Deniz C.; Tezcan, Ilhan; Al-Mousa, Hamoud; Alsum, Zobaida; Hawwari, Abbas; Metin, Ayse; Matthes-Martin, Susanne; Hoenig, Manfred; Schulz, Ansgar; Picard, Capucine; Barlogis, Vincent; Gennery, Andrew; Ifversen, Marianne; van Montfrans, JM; Kuijpers, Taco; Bredius, Robbert; Duckers, Gregor; Al-Herz, Waleed; Pai, Sung-Yun; Geha, Raif; Notheis, Gundula; Schwarze, Carl-Philipp; Tavil, Betul; Azik, Fatih; Bienemann, Kirsten; Grimbacher, Bodo; Heinz, Valerie; Gaspar, H. Bobby; Aydin, Roland; Hagl, Beate; Gathmann, Benjamin; Belohradsky, Bernd H.; Ochs, Hans D.; Chatila, Talal; Renner, Ellen D.; Su, Helen; Freeman, Alexandra F.; Engelhardt, Karin; Albert, Michael H.

    2015-01-01

    Mutations in DOCK8 result in autosomal recessive Hyper-IgE syndrome with combined immunodeficiency (CID). However, the natural course of disease, long-term prognosis, and optimal therapeutic management have not yet been clearly defined. In an international retrospective survey of patients with DOCK8

  14. In the shadow of giants: Superpower arms transfers and Third World conflict during the Cold War

    Energy Technology Data Exchange (ETDEWEB)

    Kinsella, D.T.

    1993-01-01

    This is an investigation of the impact of superpower arms transfers on interstate rivalry in the Third World during the Cold War. The study is anchored in a theoretical framework which conceives of interstate rivalry as the basis for the development of security complexes in the international system. In the case of Third World rivalries, these security complexes tend to be local in scope. The superpower security complex was global. The theoretical framework emphasizes the tendency of one security complex to encroach upon another. This study focuses on the extent to which the Cold War was externalized through the process of superpower arms transfers to local rivals. The empirical investigation consists of statistical analysis of four enduring rivalries in the Third World: those between the Arab states and Israel, Iran and Iraq, India and Pakistan, and Ethiopia and Somalia. The author employs a time-series methodology - vector autoregression - which permits a rather rigorous discrimination between cause and effect. A rigorous methodology is essential to decipher the relationship between arms transfer and interstate conflict since there is reason to suspect that causality may be mutual. Historical narratives for each of of the four rivalries facilitate an interpretation of the statistical results, but also serve to highlight anomalies. The results suggest that the impact of superpower arms transfers was most pronounced in the Middle East and the Persian Gulf. Soviet arms transfers to Egypt and Syria tended to exacerbate the Arab-Israeli rivalry. In the case of the Iran-Iraq rivalry, it was American arms transfers to Iran that were influential, but the effect appears to have been a restraining one. An action-reaction dynamic in superpower arms transfers is evident in both these cases. The statistical results are not enlightening for either the India-Pakistan or Ethiopia-Somalia rivalries. Some theoretical refinements to the security-complexes framework are suggested.

  15. Arms Control and Strategic Stability

    Institute of Scientific and Technical Information of China (English)

    Hu; Yumin

    2014-01-01

    This essay intends to offer a comment on concepts, trends and attitudes concerning arms control and strategic stability with reference to the current international security situation. It also offers observations from two different perspectives about strategic stability: one proceeds from the concept of universal security and aims to prevent conflicts and instability from disrupting regional and international security environment on which nation states depend so much for their peaceful development; the other starts from maintaining the global leadership by a super power and aiming to contain any challenge that sways or is likely to sway its dominating status. If China and the United States commit themselves to the undertaking of a new type of major powers relationship that stresses win-win cooperation, they will be able to contribute greatly to a stable international security architecture that is good for world peaceful development.

  16. Study on a 7-DOF anthropomorphic weld arm

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A kind of new obstacle space expression is proposed in this paper, in which a virtual force field (VFF) is built. Using the torque and joint optimization acted by the virtual force field on the anthropomorphic weld arm, the real-time selection of a redundant join (R-joint) is done and its equivalent virtual torque is obtained, thus the redundant joint can be controlled with whose force feedback. An inverse kinematics solution of a 6-DOF robot is applied to other six joints of the arm. Simulation experiments indicate the new inverse kinematics solution has perfect collision avoidance effect, and it is well simplified. Therefore, it can be applied to a welding task in complex operation space.

  17. The Protective Arm of the Renin Angiotensin System (RAS)

    DEFF Research Database (Denmark)

    The Protective Arm of the Renin Angiotensin System: Functional Aspects and Therapeutic Implications is the first comprehensive publication to signal the protective role of a distinct part of the renin-angiotensin system (RAS), providing readers with early insight into a complex system which...... will become of major medical importance in the near future. Focusing on recent research, The Protective Arm of the Renin Angiotensin System presents a host of new experimental studies on specific components of the RAS, namely angiotensin AT2 receptors (AT2R), the angiotensin (1-7) peptide with its receptor...... understanding of the protective side of the Renin Angiotensin System (RAS) involving angiotensin AT2 receptor, ACE2, and Ang(1-7)/Mas receptor Combines the knowledge of editors who pioneered research on the protective renin angiotensin system including; Dr. Thomas Unger, one of the founders of AT2 receptor...

  18. A Topological Implementation for Motion Planning of a Robotic Arm

    Institute of Scientific and Technical Information of China (English)

    李永成; 张Po

    1993-01-01

    An efficient path planning algorithm based on topologic method is presented in this paper.The collision free path planning for three-joint robotic arm consists of three parts:partition of C-space,construction of CN and search for a path in CN.We mainly solved the problems of partitioning the C-space and undging the connectivity between connected blocks,etc.For the motion planning of a robotic arm with a gripper,we developed the concepts of global planning and local planning,and discussed the basic factors for constructing the planning system.In the paper,some evaluation and analysis of the complexity and reliability of the algorithm are given,together with some ideas to improve the efficiency and increase the reliability.At last,some experimental results are pesented to show the efficency and accuracy of the algorithm.

  19. Sensory-Feedback Exoskeletal Arm Controller

    Science.gov (United States)

    An, Bin; Massie, Thomas H.; Vayner, Vladimir

    2004-01-01

    An electromechanical exoskeletal arm apparatus has been designed for use in controlling a remote robotic manipulator arm. The apparatus, called a force-feedback exoskeleton arm master (F-EAM) is comfortable to wear and easy to don and doff. It provides control signals from the wearer s arm to a robot arm or a computer simulator (e.g., a virtual-reality system); it also provides force and torque feedback from sensors on the robot arm or from the computer simulator to the wearer s arm. The F-EAM enables the wearer to make the robot arm gently touch objects and finely manipulate them without exerting excessive forces. The F-EAM features a lightweight design in which the motors and gear heads that generate force and torque feedback are made smaller than they ordinarily would be: this is achieved by driving the motors to power levels greater than would ordinarily be used in order to obtain higher torques, and by providing active liquid cooling of the motors to prevent overheating at the high drive levels. The F-EAM (see figure) includes an assembly that resembles a backpack and is worn like a backpack, plus an exoskeletal arm mechanism. The FEAM has five degrees of freedom (DOFs) that correspond to those of the human arm: 1. The first DOF is that of the side-to-side rotation of the upper arm about the shoulder (rotation about axis 1). The reflected torque for this DOF is provided by motor 1 via drum 1 and a planar four-bar linkage. 2. The second DOF is that of the up-and-down rotation of the arm about the shoulder. The reflected torque for this DOF is provided by motor 2 via drum 2. 3. The third DOF is that of twisting of the upper arm about its longitudinal axis. This DOF is implemented in a cable remote-center mechanism (CRCM). The reflected torque for this DOF is provided by motor 3, which drives the upper-arm cuff and the mechanism below it. A bladder inflatable by gas or liquid is placed between the cuff and the wearer s upper arm to compensate for misalignment

  20. DockBench: An Integrated Informatic Platform Bridging the Gap between the Robust Validation of Docking Protocols and Virtual Screening Simulations

    Directory of Open Access Journals (Sweden)

    Alberto Cuzzolin

    2015-05-01

    Full Text Available Virtual screening (VS is a computational methodology that streamlines the drug discovery process by reducing costs and required resources through the in silico identification of potential drug candidates. Structure-based VS (SBVS exploits knowledge about the three-dimensional (3D structure of protein targets and uses the docking methodology as search engine for novel hits. The success of a SBVS campaign strongly depends upon the accuracy of the docking protocol used to select the candidates from large chemical libraries. The identification of suitable protocols is therefore a crucial step in the setup of SBVS experiments. Carrying out extensive benchmark studies, however, is usually a tangled task that requires users’ proficiency in handling different file formats and philosophies at the basis of the plethora of existing software packages. We present here DockBench 1.0, a platform available free of charge that eases the pipeline by automating the entire procedure, from docking benchmark to VS setups. In its current implementation, DockBench 1.0 handles seven docking software packages and offers the possibility to test up to seventeen different protocols. The main features of our platform are presented here and the results of the benchmark study of human Checkpoint kinase 1 (hChk1 are discussed as validation test.

  1. Developing a cross-docking network design model under uncertain environment

    Science.gov (United States)

    Seyedhoseini, S. M.; Rashid, Reza; Teimoury, E.

    2014-09-01

    Cross-docking is a logistic concept, which plays an important role in supply chain management by decreasing inventory holding, order packing, transportation costs and delivery time. Paying attention to these concerns, and importance of the congestion in cross docks, we present a mixed-integer model to optimize the location and design of cross docks at the same time to minimize the total transportation and operating costs. The model combines queuing theory for design aspects, for that matter, we consider a network of cross docks and customers where two M/M/c queues have been represented to describe operations of indoor trucks and outdoor trucks in each cross dock. To prepare a perfect illustration for performance of the model, a real case also has been examined that indicated effectiveness of the proposed model.

  2. Two-dimensional PSD based automatic docking of self-reconfiguration modular exploration robot system

    Institute of Scientific and Technical Information of China (English)

    Zhang Liping; Ma Shugen; Li Bin; Zhang Zheng; Cao Binggang

    2007-01-01

    Based on the design of a docking mechanism, this paper thoroughly investigates the space automatic docking of self-reconfiguration modular exploration robot system (RMERS). The method that leads robot to achieve space docking by using two-dimensional PSD is put forward innovatively for the median size robot system. At the same time, in order to enlarge the detecting extension and the precision of PSD and reduce its dependence on lighting signal, the PSD was remade by increasing the optical device over its light-sensitive surface. The emission board and LED light scheduling were designed according to docking arithmetic, and the operating principle of docking process was analyzed based on these. The simulation experiments were carried out and their results are presented.

  3. Accessible high-throughput virtual screening molecular docking software for students and educators.

    Directory of Open Access Journals (Sweden)

    Reed B Jacob

    2012-05-01

    Full Text Available We survey low cost high-throughput virtual screening (HTVS computer programs for instructors who wish to demonstrate molecular docking in their courses. Since HTVS programs are a useful adjunct to the time consuming and expensive wet bench experiments necessary to discover new drug therapies, the topic of molecular docking is core to the instruction of biochemistry and molecular biology. The availability of HTVS programs coupled with decreasing costs and advances in computer hardware have made computational approaches to drug discovery possible at institutional and non-profit budgets. This paper focuses on HTVS programs with graphical user interfaces (GUIs that use either DOCK or AutoDock for the prediction of DockoMatic, PyRx, DockingServer, and MOLA since their utility has been proven by the research community, they are free or affordable, and the programs operate on a range of computer platforms.

  4. Books in Action: The Armed Services Editions.

    Science.gov (United States)

    Cole, John Y., Ed.

    In an effort to reach a wide audience, the Center for the Book in the Library of Congress presents this book in honor of the 40th anniversary celebration of the Armed Services Editions (ASE), the paperback books distributed during World War II. The titles of the essays and their authors are as follows: "The Armed Services Editions: An…

  5. Gender Integration and the Swedish Armed Forces

    DEFF Research Database (Denmark)

    Gustafsson, Daniel Marcus Sunil

    This paper discusses different gender aspects of the Swedish Armed Forces with specific references to sexual harassment and prostitution. By using the concept of Hegemonic Masculinity, sexual harassment of the women in the Swedish Armed Forces is explained in terms of a need of the men within...

  6. Homosexuality in the Dutch Armed Forces 2006

    NARCIS (Netherlands)

    Anna Adolfsen; Saskia Keuzenkamp; m.m.v. Linda Mans

    2006-01-01

    Original title: Uniform uit de kast. This study looks at the attitudes of defence personnel to homosexuality. How do members of the military view homosexual colleagues? Can gays and lesbians working in the armed forces be open about their sexual preferences? Do they regard the armed forces as a gay

  7. Why we cannot grow a human arm.

    Science.gov (United States)

    Ricci, John L

    2013-11-01

    There are several significant issues that prevent us from growing a human arm now, or within the next 10-20 years. From a tissue engineering perspective, while we can grow many of the components necessary for construction of a human arm, we can only grow them in relatively small volumes, and when scaled up to large volumes we lack the ability to develop adequate blood/nerve supply. From a genetic engineering perspective, we will probably never be able to turn on the specific genes necessary to "grow an arm" unless it is attached to a fetus and this presents enormous ethical issues related to farming of human organs and structures. Perhaps the most daunting problem facing the transplantation of a tissue engineered or transplanted arm is that of re-innervation of the structure. Since the sensory and motor nerve cells of the arm are located outside of the structure, re-innervation requires those nerves to regenerate over relatively large distances to repopulate the nervous system of the arm. This is something with which we have had little success. We can grow repair parts, but "growing an arm" presents too many insurmountable problems. The best we could possibly do with tissue engineering or genetic engineering would be the equivalent of a fetal arm and the technical problems, costs, and ethical hurdles are enormous. A more likely solution is a functional, permanent, neuroelectronically-controlled prosthesis. These are nearly a reality today.

  8. Design of a biomimetic robotic octopus arm

    Energy Technology Data Exchange (ETDEWEB)

    Laschi, C; Cianchetti, M [Advanced Robotics Technology and Systems Laboratory, Scuola Superiore Sant' Anna, Pisa (Italy); Mazzolai, B; Dario, P [Italian Institute of Technology, Genova (Italy); Mattoli, V [Centre of Research in Microengineering Laboratory, Scuola Superiore Sant' Anna, Pisa (Italy)], E-mail: cecilia.laschi@sssup.it

    2009-03-01

    This paper reports the rationale and design of a robotic arm, as inspired by an octopus arm. The octopus arm shows peculiar features, such as the ability to bend in all directions, to produce fast elongations, and to vary its stiffness. The octopus achieves these unique motor skills, thanks to its peculiar muscular structure, named muscular hydrostat. Different muscles arranged on orthogonal planes generate an antagonistic action on each other in the muscular hydrostat, which does not change its volume during muscle contractions, and allow bending and elongation of the arm and stiffness variation. By drawing inspiration from natural skills of octopus, and by analysing the geometry and mechanics of the muscular structure of its arm, we propose the design of a robot arm consisting of an artificial muscular hydrostat structure, which is completely soft and compliant, but also able to stiffen. In this paper, we discuss the design criteria of the robotic arm and how this design and the special arrangement of its muscular structure may bring the building of a robotic arm into being, by showing the results obtained by mathematical models and prototypical mock-ups.

  9. BioShaDock: a community driven bioinformatics shared Docker-based tools registry [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    François Moreews

    2015-12-01

    Full Text Available Linux container technologies, as represented by Docker, provide an alternative to complex and time-consuming installation processes needed for scientific software. The ease of deployment and the process isolation they enable, as well as the reproducibility they permit across environments and versions, are among the qualities that make them interesting candidates for the construction of bioinformatic infrastructures, at any scale from single workstations to high throughput computing architectures. The Docker Hub is a public registry which can be used to distribute bioinformatic software as Docker images. However, its lack of curation and its genericity make it difficult for a bioinformatics user to find the most appropriate images needed. BioShaDock is a bioinformatics-focused Docker registry, which provides a local and fully controlled environment to build and publish bioinformatic software as portable Docker images. It provides a number of improvements over the base Docker registry on authentication and permissions management, that enable its integration in existing bioinformatic infrastructures such as computing platforms. The metadata associated with the registered images are domain-centric, including for instance concepts defined in the EDAM ontology, a shared and structured vocabulary of commonly used terms in bioinformatics. The registry also includes user defined tags to facilitate its discovery, as well as a link to the tool description in the ELIXIR registry if it already exists. If it does not, the BioShaDock registry will synchronize with the registry to create a new description in the Elixir registry, based on the BioShaDock entry metadata. This link will help users get more information on the tool such as its EDAM operations, input and output types. This allows integration with the ELIXIR Tools and Data Services Registry, thus providing the appropriate visibility of such images to the bioinformatics community.

  10. Docking of anti-HIV-1 oxoquinoline-acylhydrazone derivatives as potential HSV-1 DNA polymerase inhibitors

    Science.gov (United States)

    Yoneda, Julliane Diniz; Albuquerque, Magaly Girão; Leal, Kátia Zaccur; Santos, Fernanda da Costa; Batalha, Pedro Netto; Brozeguini, Leonardo; Seidl, Peter R.; de Alencastro, Ricardo Bicca; Cunha, Anna Cláudia; de Souza, Maria Cecília B. V.; Ferreira, Vitor F.; Giongo, Viveca A.; Cirne-Santos, Cláudio; Paixão, Izabel C. P.

    2014-09-01

    Although there are many antiviral drugs available for the treatment of herpes simplex virus (HSV) infections, still the synthesis of new anti-HSV candidates is an important strategy to be pursued, due to the emergency of resistant HSV strains mainly in human immunodeficiency virus (HIV) co-infected patients. Some 1,4-dihydro-4-oxoquinolines, such as PNU-183792 (1), show a broad spectrum antiviral activity against human herpes viruses, inhibiting the viral DNA polymerase (POL) without affecting the human POLs. Thus, on an ongoing antiviral research project, our group has synthesized ribonucleosides containing the 1,4-dihydro-4-oxoquinoline (quinolone) heterocyclic moiety, such as the 6-Cl derivative (2), which is a dual antiviral agent (HSV-1 and HIV-1). Molecular dynamics simulations of the complexes of 1 and 2 with the HSV-1 POL suggest that structural modifications of 2 should increase its experimental anti-HSV-1 activity, since its ribosyl and carboxyl groups are highly hydrophilic to interact with a hydrophobic pocket of this enzyme. Therefore, in this work, comparative molecular docking simulations of 1 and three new synthesized oxoquinoline-acylhydrazone HIV-1 inhibitors (3-5), which do not contain those hydrophilic groups, were carried out, in order to access these modifications in the proposition of new potential anti-HSV-1 agents, but maintaining the anti-HIV-1 activity. Among the docked compounds, the oxoquinoline-acylhydrazone 3 is the best candidate for an anti-HSV-1 agent, and, in addition, it showed anti-HIV-1 activity (EC50 = 3.4 ± 0.3 μM). Compounds 2 and 3 were used as templates in the design of four new oxoquinoline-acylhydrazones (6-9) as potential anti-HSV-1 agents to increase the antiviral activity of 2. Among the docked compounds, oxoquinoline-acylhydrazone 7 was selected as the best candidate for further development of dual anti-HIV/HSV activity.

  11. Cryo-scanning electron microscopy investigation of the Octopus Vulgaris arm structures for the design of an octopus-like arm artefact.

    Science.gov (United States)

    Minnocci, Antonio; Cianchetti, Matteo; Mazzolai, Barbara; Sebastiani, Luca; Laschi, Cecilia

    2015-12-01

    Octopus vulgaris is a cephalopod of the Octopodidae family. It has four pairs of arms and two rows of suckers which perform many functions, including bending and elongation. For this reason the octopus was chosen as model to develop a new generation of soft-body robots. In order to explain some of the fine structures of the octopus arm in relation to its specific ability, we examined the external and internal structures of O. vulgaris arms in a frozen-hydrated state using cryo-scanning electron microscopy. The arms showed skin with a very complex design that is useful to elongation, and a pore pattern distribution on their surface which is functional to cutaneous oxygen uptake. The analysis of freeze-fractured frozen-hydrated arm samples allowed us to describe the developmental differences in the relative proportion of the areas of axial nerve cord, intrinsic and extrinsic musculature, in relation to the growth of the arms and of the increase in functional capability. In the suckers, we analyzed the shedding mechanisms in the outer part of the infundibulum and described the outer and inner characteristics of the denticles, showing in detail their pore system, which is fundamental for their ability to explore the environment. These results are discussed by considering their possible application in the design of new octopus-like artefacts, which will be able to take advantage of some of these ultrastructure characteristics and achieve advanced bioinspired functionalities.

  12. MOLS 2.0: software package for peptide modeling and protein-ligand docking.

    Science.gov (United States)

    Paul, D Sam; Gautham, N

    2016-10-01

    We previously developed an algorithm to perform conformational searches of proteins and peptides, and to perform the docking of ligands to protein receptors. In order to identify optimal conformations and docked poses, this algorithm uses mutually orthogonal Latin squares (MOLS) to rationally sample the vast conformational (or docking) space, and then analyzes this relatively small sample using a variant of mean field theory. The conformational search part of the algorithm was denoted MOLS 1.0. The docking portion of the algorithm, which allows only "flexible ligand/rigid receptor" docking, was denoted MOLSDOCK. Both are FORTRAN-based command-line-only molecular docking computer programs, though a GUI was developed later for MOLS 1.0. Both the conformational search and the rigid receptor docking parts of the algorithm have been extensively validated. We have now further enhanced the capabilities of the program by incorporating "induced fit" side-chain receptor flexibility for docking peptide ligands. Benchmarking and extensive testing is now being carried out for the flexible receptor portion of the docking. Additionally, to make both the peptide conformational search and docking algorithms (the latter including both flexible ligand/rigid receptor and flexible ligand/flexible receptor techniques) more accessible to the research community, we have developed MOLS 2.0, which incorporates a new Java-based graphical user interface (GUI). Here, we give a detailed description of MOLS 2.0. The source code and binary for MOLS 2.0 are distributed free (under a GNU Lesser General Public License) to the scientific community. They are freely available for download at https://sourceforge.net/projects/mols2-0/files/ .

  13. Identification of promising DNA GyrB inhibitors for Tuberculosis using pharmacophore-based virtual screening, molecular docking and molecular dynamics studies.

    Science.gov (United States)

    Islam, Md Ataul; Pillay, Tahir S

    2017-01-21

    In this study, we searched for potential DNA GyrB inhibitors using pharmacophore-based virtual screening followed by molecular docking and molecular dynamics simulation approaches. For this purpose, a set of 248 DNA GyrB inhibitors was collected from the literature and a well-validated pharmacophore model was generated. The best pharmacophore model explained that two each of hydrogen bond acceptors and hydrophobicity regions were critical for inhibition of DNA GyrB. Good statistical results of the pharmacophore model indicated that the model was robust in nature. Virtual screening of molecular databases revealed three molecules as potential antimycobacterial agents. The final screened promising compounds were evaluated in molecular docking and molecular dynamics simulation studies. In the molecular dynamics studies, RMSD and RMSF values undoubtedly explained that the screened compounds formed stable complexes with DNA GyrB. Therefore, it can be concluded that the compounds identified may have potential for the treatment of TB.

  14. Design And Implementation Of Anthropomorphic Robotic Arm

    Directory of Open Access Journals (Sweden)

    Ashish Sharma

    2014-01-01

    Full Text Available The report focuses on the design and demonstration of an anthropomorphic robotic arm with seven degrees of freedom using readily available low-cost components to perform different real time human hand applications. The robotic arm consists of a shoulder, elbow, wrist and a five-finger gripper. It can perform different gripping actions, such as lateral, spherical, cylindrical and tip-holding gripping actions; each finger has three movable links. The actuator used for the robotic arm is a high torque dc servo motor and the five-finger gripper consists of five cables placed like tendons in the human arm. Implementation is done using a human hand glove which senses the motion from sensor technology to produce a proportional analog voltage, digitized via the microcontroller Atmel ATmega32. The microcontroller then through the processed signal controls the mechanical structure that is the robotic arm. Keywords –

  15. Synthesis and docking studies of novel antitumor benzimidazoles.

    Science.gov (United States)

    Omar, Mohamed A; Shaker, Yasser M; Galal, Shadia A; Ali, Mamdouh M; Kerwin, Sean M; Li, Jing; Tokuda, Harukuni; Ramadan, Raghda A; El Diwani, Hoda I

    2012-12-15

    In this work, the benzimidazole-pyrrole conjugates 6a-h and benzimidazole-tetracycles conjugates 12-14 were prepared. The cytotoxicity of the compounds 3, 4a-h, 6a-h, 8, 10 and 12-14 was tested against lung cancer cell line A549. Compound 6b exhibited higher activity than the bis-benzoxazole natural product (UK-1), the standard. The tested 4g,h, 6a-h, 10 and 12-14 exhibited remarkable cytotoxicity activity against breast cancer cell line MCF-7 with higher activity than tamoxifen. Furthermore, compound 4h was found to be also more potent than doxurubicin. The antitumor promotion activity of synthesized compounds 4g,h, 6a-h, 10 and 12-14 has been estimated by studying their possible inhibitory effects on EBV-EA activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Among the studied compounds, the inhibitory activities of compounds 8, 13 and 14 demonstrated strong inhibitory effects on the Epstein-Barr virus early antigen (EBV-EA) activation without showing any cytotoxicity on the Raji cells and their effects being stronger than that of a representative control, oleanolic acid. Moreover, the molecular docking of the new compounds into plasminogen activator (uPA) receptor has been in correlation with the antitumor activity. All synthesized compounds 3, 4a-h, 6a-h, 8, 10 and 12-14 were docked into same groove of the binding site of the native co-crystalized (4-iodobenzo[b]thiophene-2-carboxamidine) ligand (PDB code:1c5x) for activity explaination. Compounds 4h, 6b and 13, giving the best docking results, were further studied to estimate their effect on the level of uPA using AssayMax human urokinase (uPA) ELISA kit. In case of A549 cell line, compound 6 exhibited similar activity to MMC, and for MCF-7 cell line, compound 4h exhibited similar activity to doxorubicin, in inhibiting the expression of uPA.

  16. CyARM: Haptic Sensing Device for Spatial Localization on Basis of Exploration by Arms

    Directory of Open Access Journals (Sweden)

    Junichi Akita

    2009-01-01

    Full Text Available We introduce a new type of perception aid device based on user's exploration action, which is named as CyARM (acronym of “Cyber Arm”. The user holds this device in her/his arm, the extension of the arm is controlled by tension in wires, which are attached to her/his body according to the distance to the object. This user interface has unique characteristics that give users the illusion of an imaginary arm that extends to existing objects. The implementations of CyARM and our two experiments to investigate the efficiency and effectiveness of CyARM are described. The results show that we could confirm that CyARM can be used to recognize the presence of an object in front of the user and to measure the relative distance to the object.

  17. Investigating the Inhibitory Effect of Wortmannin in the Hotspot Mutation at Codon 1047 of PIK3CA Kinase Domain: A Molecular Docking and Molecular Dynamics Approach.

    Science.gov (United States)

    Kumar, D Thirumal; Doss, C George Priya

    2016-01-01

    Oncogenic mutations in phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) are the most frequently reported in association with various forms of cancer. Several studies have reported the significance of hotspot mutations in a catalytic subunit of PIK3CA in association with breast cancer. Mutations are frequently observed in the highly conserved region of the kinase domain (797-1068 amino acids) of PIK3CA are activating or gain-of-function mutations. Mutation in codon 1047 occurs in the C-terminal region of the kinase domain with histidine (H) replaced by arginine (R), lysine (L), and tyrosine (Y). Pathogenicity and protein stability predictors PhD-SNP, Align GVGD, HANSA, iStable, and MUpro classified H1047R as highly deleterious when compared to H1047L and H1047Y. To explore the inhibitory activity of Wortmannin toward PIK3CA, the three-dimensional structure of the mutant protein was determined using homology modeling followed by molecular docking and molecular dynamics analysis. Docking studies were performed for the three mutants and native with Wortmannin to measure the differences in their binding pattern. Comparative docking study revealed that H1047R-Wortmannin complex has a higher number of hydrogen bonds as well as the best binding affinity next to the native protein. Furthermore, 100 ns molecular dynamics simulation was initiated with the docked complexes to understand the various changes induced by the mutation. Though Wortmannin was found to nullify the effect of H1047R over the protein, further studies are required for designing a better compound. As SNPs are major genetic variations observed in disease condition, personalized medicine would provide enhanced drug therapy.

  18. Synthesis, Evaluation and Docking studies of Cholecalciferol Derivative

    Directory of Open Access Journals (Sweden)

    Sultanat

    2014-09-01

    Full Text Available Improved synthesis of 3b-acetoxy-9, 10-seco-19, 8(8-spiro-5(10, 6-cholestadiene has been reported after reacting cholecalciferol acetate with dimethylbutadiene by incorporating BF3·OEt2, SnCl4, ZnBr2, p-TsOH in toluene under Diels-Alder condition to get better yields. Agarose gel electrophoresis showed the potential in vitro DNA damaging nature while as the comet assay depicted the genotoxic nature by mobilizing the tail of the comet in lymphocytes. The molecular docking depicted the intercalation of steroid derivative with minor groove of the DNA molecule and in this configuration the phosphodiester bond of DNA stabilizes the acetoxy group. The bioactivity score and PASS software analysis confirmed the potential physicochemical features of the compound to act as active drug.

  19. Vision Based Navigation Sensors for Spacecraft Rendezvous and Docking

    DEFF Research Database (Denmark)

    Benn, Mathias

    . Denmark has, with DTUs design of the Swarm mission, ESAs next Earth Observation Programme magnetic mapping mission, and DTUs participation in GRACE, ELISA and Alsat2, a leading role in designing and verifying sensor systems for this new class of spacecraft. The Swedish led PRISMA mission...... is a technological demonstration mission, where all aspects of space rendezvous and docking to both a cooperative and a non-cooperative target is researched, with the use of novel methods, instruments and technologies. Amongst other equipment, DTU has delivered a vision based sensor package to the Main spacecraft...... of this constellation, providing both position and pose information for the Target vehicle. This dissertation will describe the study, implementation and verification methods that has led to the realization of this optical Vision Based Sensor (VBS), which is used on the PRISMA mission. On June 15th 2010 the PRISMA...

  20. FACILE SYNTHESIS, DOCKING STUDIES AND ANTIOXIDANT ACTIVITY OF FGVR

    Directory of Open Access Journals (Sweden)

    Himaja M

    2011-08-01

    Full Text Available A rational designing of linear Tetrapeptide FGVR was done and was synthesized by solution phase peptide synthesis. The docking studies of designed linear tetrapeptide FGVR was carried out by using Schrodinger Software Solutions, USA. Qikprop results show the ligand FGVR mostly act as antihypertensive and anti coagulant properties. The solution phase synthesis of FGVR is carried out by using 1-Ethyl-3-(3-dimethylaminopropyl carbodiimide (EDC as coupling agents and N-Methyl morpholine (NMM as base. Structure of synthesized FGVR was confirmed by FTIR, 1H NMR and Mass spectral data, and evaluated for antioxidant property by using 1,1-diphenyl-2-picryl-hydrazil (DPPH. method and the synthesized peptides FGVR possess moderate antioxidant activity.

  1. SYNTHESIS, DOCKING STUDIES AND ANTIOXIDANT ACTIVITY OF TETRAPEPTIDE FGVY

    Directory of Open Access Journals (Sweden)

    Md. Abdulla

    2011-03-01

    Full Text Available A rational designing of linear Tetrapeptide FGVY was done and was synthesized by solution phase peptide synthesis. The docking studies of designed linear tetrapeptide FGVY was carried out by using Schrodinger Software Solutions, USA. Qikprop results show the ligand FGVY mostly act as antihypertensive and anti coagulant properties. The solution phase synthesis of FGVY is carried out by using Dicyclohexyl carbodiimide (DCC as coupling agents and triethyl amine as base. Structure of synthesized FGVY was confirmed by FTIR, 1H NMR and Mass spectral data, and evaluated for antioxidant property by using 1,1-diphenyl-2-picryl-hydrazil (DPPH. method and the synthesized peptides FGVY possess moderate antioxidant activity.

  2. On the analysis of protein-protein interactions via knowledge-based potentials for the prediction of protein-protein docking

    DEFF Research Database (Denmark)

    Feliu, Elisenda; Aloy, Patrick; Oliva, Baldo

    2011-01-01

    Development of effective methods to screen binary interactions obtained by rigid-body protein-protein docking is key for structure prediction of complexes and for elucidating physicochemical principles of protein-protein binding. We have derived empirical knowledge-based potential functions...... results were compared with a residue-pair potential scoring function (RPScore) and an atomic-detailed scoring function (Zrank). We have combined knowledge-based potentials to score protein-protein poses of decoys of complexes classified either as transient or as permanent protein-protein interactions...

  3. Continuous neuronal ensemble control of simulated arm reaching by a human with tetraplegia

    Science.gov (United States)

    Chadwick, E. K.; Blana, D.; Simeral, J. D.; Lambrecht, J.; Kim, S. P.; Cornwell, A. S.; Taylor, D. M.; Hochberg, L. R.; Donoghue, J. P.; Kirsch, R. F.

    2011-06-01

    Functional electrical stimulation (FES), the coordinated electrical activation of multiple muscles, has been used to restore arm and hand function in people with paralysis. User interfaces for such systems typically derive commands from mechanically unrelated parts of the body with retained volitional control, and are unnatural and unable to simultaneously command the various joints of the arm. Neural interface systems, based on spiking intracortical signals recorded from the arm area of motor cortex, have shown the ability to control computer cursors, robotic arms and individual muscles in intact non-human primates. Such neural interface systems may thus offer a more natural source of commands for restoring dexterous movements via FES. However, the ability to use decoded neural signals to control the complex mechanical dynamics of a reanimated human limb, rather than the kinematics of a computer mouse, has not been demonstrated. This study demonstrates the ability of an individual with long-standing tetraplegia to use cortical neuron recordings to command the real-time movements of a simulated dynamic arm. This virtual arm replicates the dynamics associated with arm mass and muscle contractile properties, as well as those of an FES feedback controller that converts user commands into the required muscle activation patterns. An individual with long-standing tetraplegia was thus able to control a virtual, two-joint, dynamic arm in real time using commands derived from an existing human intracortical interface technology. These results show the feasibility of combining such an intracortical interface with existing FES systems to provide a high-performance, natural system for restoring arm and hand function in individuals with extensive paralysis. This paper was originally submitted for the special issue containing contributions from the Fourth International Brain-Computer Interface Meeting.

  4. The arms race between fishers

    Science.gov (United States)

    Rijnsdorp, Adriaan D.; Poos, Jan Jaap; Quirijns, Floor J.; HilleRisLambers, Reinier; De Wilde, Jan W.; Den Heijer, Willem M.

    An analysis of the changes in the Dutch demersal fishing fleet since the 1950s revealed that competitive interactions among vessels and gear types within the constraints imposed by biological, economic and fisheries management factors are the dominant processes governing the dynamics of fishing fleets. Double beam trawling, introduced in the early 1960s, proved a successful fishing method to catch deep burying flatfish, in particular sole. In less than 10 years, the otter trawl fleet was replaced by a highly specialised beam trawling fleet, despite an initial doubling of the loss rate of vessels due to stability problems. Engine power, size of the beam trawl, number of tickler chains and fishing speed rapidly increased and fishing activities expanded into previously lightly fished grounds and seasons. Following the ban on flatfish trawling within the 12 nautical mile zone for vessels of more than 300 hp in 1975 and with the restriction of engine power to 2000 hp in 1987, the beam trawl fleet bifurcated. Changes in the fleet capacity were related to the economic results and showed a cyclic pattern with a period of 6-7 years. The arms race between fishers was fuelled by competitive interactions among fishers: while the catchability of the fleet more than doubled in the ten years following the introduction of the beam trawl, a decline in catchability was observed in reference beam trawlers that remained the same. Vessel performance was not only affected by the technological characteristics but also by the number and characteristics of competing vessels.

  5. Youth Armed Groups in Colombia

    Directory of Open Access Journals (Sweden)

    Linda Dale

    2014-09-01

    Full Text Available For the many years of Colombia’s civil war, youth have been trying to find their way in complicated and dangerous situations. A central component of this is their relationship with armed groups, something that has evolved considerably over the past ten years. This practice note examines the context within which these connections are formed and the implications this has for self/social identity and meaningful resistance. The ideas in this practice note are based on consultations with young Colombians, particularly those displaced from 2000-2013. These sessions included art activities, focus groups and individual interviews. Art activities involved descriptive and expressive projects so that participants could explore their feelings and memories of situations and experiences. This provided a base for group discussions where youth exchanged information and debated issues. A total of 34 workshops were held over a twelve year period. These consultations revealed how war flows all over young people, touching every aspect of their identity. The boundaries between the personal and political no longer exist in today’s civil wars, if indeed they every truly did. Young people growing up inside Colombia’s war understand this at a deep level. An acknowledgement of this pain – showing the connections between the personal and political dimensions of war – is, they would maintain, the basis for their personal healing as well as an important tool for the building of sustainable peace.

  6. Pharmacophore Modeling and Molecular Docking Studies on Pinus roxburghii as a Target for Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Pawan Kaushik

    2014-01-01

    Full Text Available The present study attempts to establish a relationship between ethnopharmacological claims and bioactive constituents present in Pinus roxburghii against all possible targets for diabetes through molecular docking and to develop a pharmacophore model for the active target. The process of molecular docking involves study of different bonding modes of one ligand with active cavities of target receptors protein tyrosine phosphatase 1-beta (PTP-1β, dipeptidyl peptidase-IV (DPP-IV, aldose reductase (AR, and insulin receptor (IR with help of docking software Molegro virtual docker (MVD. From the results of docking score values on different receptors for antidiabetic activity, it is observed that constituents, namely, secoisoresinol, pinoresinol, and cedeodarin, showed the best docking results on almost all the receptors, while the most significant results were observed on AR. Then, LigandScout was applied to develop a pharmacophore model for active target. LigandScout revealed that 2 hydrogen bond donors pointing towards Tyr 48 and His 110 are a major requirement of the pharmacophore generated. In our molecular docking studies, the active constituent, secoisoresinol, has also shown hydrogen bonding with His 110 residue which is a part of the pharmacophore. The docking results have given better insights into the development of better aldose reductase inhibitor so as to treat diabetes related secondary complications.

  7. Proposed docking interface between peptidoglycan and the target recognition domain of zoocin A

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yinghua [Department of Chemistry, University of Alabama, Tuscaloosa, AL 35487 (United States); Simmonds, Robin S. [Department of Microbiology and Immunology, University of Otago, Dunedin (New Zealand); Timkovich, Russell, E-mail: rtimkovi@bama.ua.edu [Department of Chemistry, University of Alabama, Tuscaloosa, AL 35487 (United States)

    2013-11-15

    Highlights: •Peptidoglycan added to zoocin rTRD perturbs NMR resonances around W115. •Simulations predict docking to a shallow surface groove near W115. •The docking interface is similar to mammalian antibody–antigen sites. •EDTA binds to a distinct surface site. -- Abstract: A docking model is proposed for the target recognition domain of the lytic exoenzyme zoocin A with the peptidoglycan on the outer cell surface of sensitive bacterial strains. Solubilized fragments from such peptidoglycans perturb specific backbone and side chain amide resonances in the recombinant form of the domain designated rTRD as detected in two-dimensional {sup 1}H–{sup 15}N correlation NMR spectra. The affected residues comprise a shallow surface cleft on the protein surface near W115, N53, N117, and Q105 among others, which interacts with the peptide portion of the peptidoglycan. Calculations with AutoDock Vina provide models of the docking interface. There is approximate homology between the rTDR-peptidoglycan docking site and the antigen binding site of Fab antibodies with the immunoglobin fold. EDTA was also found to bind to rTRD, but at a site distinct from the proposed peptidoglycan docking site.

  8. Dissecting docking and tethering of secretory vesicles at the target membrane

    Science.gov (United States)

    Toonen, Ruud F; Kochubey, Olexiy; de Wit, Heidi; Gulyas-Kovacs, Attila; Konijnenburg, Bas; Sørensen, Jakob B; Klingauf, Jurgen; Verhage, Matthijs

    2006-01-01

    Secretory vesicles dock at their target in preparation for fusion. Using single-vesicle total internal reflection fluorescence microscopy in chromaffin cells, we show that most approaching vesicles dock only transiently, but that some are captured by at least two different tethering modes, weak and strong. Both vesicle delivery and tethering depend on Munc18-1, a known docking factor. By decreasing the amount of cortical actin by Latrunculin A application, morphological docking can be restored artificially in docking-deficient munc18-1 null cells, but neither strong tethering nor fusion, demonstrating that morphological docking is not sufficient for secretion. Deletion of the t-SNARE and Munc18-1 binding partner syntaxin, but not the v-SNARE synaptobrevin/VAMP, also reduces strong tethering and fusion. We conclude that docking vesicles either undock immediately or are captured by minimal tethering machinery and converted in a munc18-1/syntaxin-dependent, strongly tethered, fusion-competent state. PMID:16902411

  9. Resveratrol inhibits matrix metalloproteinases to attenuate neuronal damage in cerebral ischemia:a molecular docking study exploring possible neuroprotection

    Institute of Scientific and Technical Information of China (English)

    Anand Kumar Pandey; Pallab Bhattacharya; Swet Chand Shukla; Sudip Paul; Ranjana Patnaik

    2015-01-01

    The main pathophysiology of cerebral ischemia is the structural alteration in the neurovascular unit, coinciding with neurovascular matrix degradation. Resveratrol has been reported to be one of the most potent chemopreventive agents that can inhibit cellular processes associated with ischemic stroke. Matrix metalloproteinases (MMPs) has been considered as a potential drug target for the treatment of cerebral ischemia. To explore this, we tried to investigate the inter-action of resveratrol with MMPs through molecular docking studies. At 30 minutes before and 2 hours after cerebral ischemia/reperfusion induced by occlusion of the middle cerebral artery, 40 mg/kg resveratrol was intraperitoneally administered. After resveratrol administration, neu-rological function and brain edema were significantly alleviated, cerebral infarct volume was signiifcantly reduced, and nitrite and malondialdehyde levels in the cortical and striatal regions were signiifcantly decreased. The molecular docking study of resveratrol and MMPs revealed that resveratrol occupied the active site of MMP-2 and MMP-9. The binding energy of the complexes was –37.848672 kJ/mol and –36.6345 kJ/mol for MMP-2 and MMP-9, respectively. In case of MMP-2, Leu 164, Ala 165 and Thr 227 were engaged in H-Bonding with resveratrol and in case of MMP-9, H-bonding was found with Glu 402, Ala 417 and Arg 424 residues. These ifndings collectively reveal that resveratrol exhibits neuroprotective effects on cerebral ischemia through inhibiting MMP-2 and MMP-9 activity.

  10. Study on the interaction of the epilepsy drug, zonisamide with human serum albumin (HSA) by spectroscopic and molecular docking techniques

    Science.gov (United States)

    Shahabadi, Nahid; Khorshidi, Aref; Moghadam, Neda Hossinpour

    2013-10-01

    In the present investigation, an attempt has been made to study the interaction of zonisamide (ZNS) with the transport protein, human serum albumin (HSA) employing UV-Vis, fluorometric, circular dichroism (CD) and molecular docking techniques. The results indicated that binding of ZNS to HSA caused strong fluorescence quenching of HSA through static quenching mechanism, hydrogen bonds and van der Waals contacts are the major forces in the stability of protein ZNS complex and the process of the binding of ZNS with HSA was driven by enthalpy (ΔH = -193.442 kJ mol-1). The results of CD and UV-Vis spectroscopy showed that the binding of this drug to HSA induced conformational changes in HSA. Furthermore, the study of molecular docking also indicated that zonisamide could strongly bind to the site I (subdomain IIA) of HSA mainly by hydrophobic interaction and there were hydrogen bond interactions between this drug and HSA, also known as the warfarin binding site.

  11. In silico designing breast cancer peptide vaccine for binding to MHC class I and II: A molecular docking study.

    Science.gov (United States)

    Mahdavi, Manijeh; Moreau, Violaine

    2016-12-01

    Antigenic peptides or cancer peptide vaccines can be directly delivered to cancer patients to produce immunologic responses against cancer cells. Specifically, designed peptides can associate with Major Histocompatibility Complex (MHC) class I or II molecules on the cell surface of antigen presenting cells activating anti-tumor effector mechanisms by triggering helper T cell (Th) or cytotoxic T cells (CTL). In general, high binding to MHCs approximately correlates with in vivo immunogenicity. Consequently, a molecular docking technique was run on a library of novel discontinuous peptides predicted by PEPOP from Human epidermal growth factor receptor 2 (HER2 ECD) subdomain III. This technique is expected to improve the prediction accuracy in order to identify the best MHC class I and II binder peptides. Molecular docking analysis through GOLD identified the peptide 1412 as the best MHC binder peptide to both MHC class I and II molecules used in the study. The GOLD results predicted HLA-DR4, HLA-DP2 and TCR as the most often targeted receptors by the peptide 1412. These findings, based on bioinformatics analyses, can be exploited in further experimental analyses in vaccine design and cancer therapy to find possible proper approaches providing beneficial effects.

  12. Investigating the importance of Delaunay-based definition of atomic interactions in scoring of protein-protein docking results.

    Science.gov (United States)

    Jafari, Rahim; Sadeghi, Mehdi; Mirzaie, Mehdi

    2016-05-01

    The approaches taken to represent and describe structural features of the macromolecules are of major importance when developing computational methods for studying and predicting their structures and interactions. This study attempts to explore the significance of Delaunay tessellation for the definition of atomic interactions by evaluating its impact on the performance of scoring protein-protein docking prediction. Two sets of knowledge-based scoring potentials are extracted from a training dataset of native protein-protein complexes. The potential of the first set is derived using atomic interactions extracted from Delaunay tessellated structures. The potential of the second set is calculated conventionally, that is, using atom pairs whose interactions were determined by their separation distances. The scoring potentials were tested against two different docking decoy sets and their performances were compared. The results show that, if properly optimized, the Delaunay-based scoring potentials can achieve higher success rate than the usual scoring potentials. These results and the results of a previous study on the use of Delaunay-based potentials in protein fold recognition, all point to the fact that Delaunay tessellation of protein structure can provide a more realistic definition of atomic interaction, and therefore, if appropriately utilized, may be able to improve the accuracy of pair potentials.

  13. Insights into the structure and inhibition of Giardia intestinalis arginine deiminase: homology modeling, docking, and molecular dynamics studies.

    Science.gov (United States)

    Trejo-Soto, Pedro Josué; Aguayo-Ortiz, Rodrigo; Yépez-Mulia, Lilián; Hernández-Campos, Alicia; Medina-Franco, José Luis; Castillo, Rafael

    2016-01-01

    Giardia intestinalis arginine deiminase (GiADI) is an important metabolic enzyme involved in the energy production and defense of this protozoan parasite. The lack of this enzyme in the human host makes GiADI an attractive target for drug design against G. intestinalis. One approach in the design of inhibitors of GiADI could be computer-assisted studies of its crystal structure, such as docking; however, the required crystallographic structure of the enzyme still remains unresolved. Because of its relevance, in this work, we present a three-dimensional structure of GiADI obtained from its amino acid sequence using the homology modeling approximation. Furthermore, we present an approximation of the most stable dimeric structure of GiADI identified through molecular dynamics simulation studies. An in silico analysis of druggability using the structure of GiADI was carried out in order to know if it is a good target for design and optimization of selective inhibitors. Potential GiADI inhibitors were identified by docking of a set of 3196 commercial and 19 in-house benzimidazole derivatives, and molecular dynamics simulation studies were used to evaluate the stability of the ligand-enzyme complexes.

  14. Resveratrol inhibits matrix metalloproteinases to attenuate neuronal damage in cerebral ischemia: a molecular docking study exploring possible neuroprotection

    Directory of Open Access Journals (Sweden)

    Anand Kumar Pandey

    2015-01-01

    Full Text Available The main pathophysiology of cerebral ischemia is the structural alteration in the neurovascular unit, coinciding with neurovascular matrix degradation. Resveratrol has been reported to be one of the most potent chemopreventive agents that can inhibit cellular processes associated with ischemic stroke. Matrix metalloproteinases (MMPs has been considered as a potential drug target for the treatment of cerebral ischemia. To explore this, we tried to investigate the interaction of resveratrol with MMPs through molecular docking studies. At 30 minutes before and 2 hours after cerebral ischemia/reperfusion induced by occlusion of the middle cerebral artery, 40 mg/kg resveratrol was intraperitoneally administered. After resveratrol administration, neurological function and brain edema were significantly alleviated, cerebral infarct volume was significantly reduced, and nitrite and malondialdehyde levels in the cortical and striatal regions were significantly decreased. The molecular docking study of resveratrol and MMPs revealed that resveratrol occupied the active site of MMP-2 and MMP-9. The binding energy of the complexes was -37.848672 kJ/mol and -36.6345 kJ/mol for MMP-2 and MMP-9, respectively. In case of MMP-2, Leu 164, Ala 165 and Thr 227 were engaged in H-Bonding with resveratrol and in case of MMP-9, H-bonding was found with Glu 402, Ala 417 and Arg 424 residues. These findings collectively reveal that resveratrol exhibits neuroprotective effects on cerebral ischemia through inhibiting MMP-2 and MMP-9 activity.

  15. ADMET, Docking studies & binding energy calculations of some Novel ACE - inhibitors for the treatment of Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Gade Deepak Reddy

    2012-09-01

    Full Text Available Diabetic Nephropathy (DN is one of the major complications of diabetes mellitus, representing the leading of cause of chronic renal disease and a major cause of morbidity and mortality in both type 1 and type 2 diabetic patients. The Renin-Angiotensin-Aldosterone System (RAAS has been implicated in the pathophysiology of DN, and suggests a therapeutic target for blocking this system. Therefore, inhibition of RAAS plays a crucial role in the treatment of DN and therapeutic intervention mostly involves administration of angiotensin converting enzyme (ACE inhibitors and angiotensin AT1 receptor blockers. In this current study, we have used computational methods to design 37 novel ACE-inhibitors and evaluated them for the interaction with the enzyme ACE through insilico analysis. The obtained results were compared with the standard drug enalapril to find out the potential inhibitors. Here we report that ligand 4 exhibited strongest inhibitory activity among all. All the analogs are also screened for their ADME & Toxicity profiles using insilico tools and ligand 9 is having better binding affinity next to ligand 4, and also having better ADMET profile when compared to that of ligand 4. Post docking calculations were also performed for the docked complexes in order to identify the individual ligand binding energies by employing Multi-Ligand Bimolecular Association with Energetics (Embrace

  16. ARM Climate Research Facility Annual Report 2005

    Energy Technology Data Exchange (ETDEWEB)

    J. Voyles

    2005-12-31

    Through the ARM Program, the DOE funded the development of several highly instrumented ground stations for studying cloud formation processes and their influence on radiative transfer, and for measuring other parameters that determine the radiative properties of the atmosphere. This scientific infrastructure, and resultant data archive, is a valuable national and international asset for advancing scientific knowledge of Earth systems. In fiscal year (FY) 2003, the DOE designated ARM sites as a national scientific user facility: the ARM Climate Research (ACRF). The ACRF has enormous potential to contribute to a wide range interdisciplinary science in areas such as meteorology, atmospheric aerosols, hydrology, biogeochemical cycling, and satellite validation, to name only a few.

  17. GeauxDock: Accelerating Structure-Based Virtual Screening with Heterogeneous Computing

    Science.gov (United States)

    Fang, Ye; Ding, Yun; Feinstein, Wei P.; Koppelman, David M.; Moreno, Juana; Jarrell, Mark; Ramanujam, J.; Brylinski, Michal

    2016-01-01

    Computational modeling of drug binding to proteins is an integral component of direct drug design. Particularly, structure-based virtual screening is often used to perform large-scale modeling of putative associations between small organic molecules and their pharmacologically relevant protein targets. Because of a large number of drug candidates to be evaluated, an accurate and fast docking engine is a critical element of virtual screening. Consequently, highly optimized docking codes are of paramount importance for the effectiveness of virtual screening methods. In this communication, we describe the implementation, tuning and performance characteristics of GeauxDock, a recently developed molecular docking program. GeauxDock is built upon the Monte Carlo algorithm and features a novel scoring function combining physics-based energy terms with statistical and knowledge-based potentials. Developed specifically for heterogeneous computing platforms, the current version of GeauxDock can be deployed on modern, multi-core Central Processing Units (CPUs) as well as massively parallel accelerators, Intel Xeon Phi and NVIDIA Graphics Processing Unit (GPU). First, we carried out a thorough performance tuning of the high-level framework and the docking kernel to produce a fast serial code, which was then ported to shared-memory multi-core CPUs yielding a near-ideal scaling. Further, using Xeon Phi gives 1.9× performance improvement over a dual 10-core Xeon CPU, whereas the best GPU accelerator, GeForce GTX 980, achieves a speedup as high as 3.5×. On that account, GeauxDock can take advantage of modern heterogeneous architectures to considerably accelerate structure-based virtual screening applications. GeauxDock is open-sourced and publicly available at www.brylinski.org/geauxdock and https://figshare.com/articles/geauxdock_tar_gz/3205249. PMID:27420300

  18. GeauxDock: Accelerating Structure-Based Virtual Screening with Heterogeneous Computing.

    Directory of Open Access Journals (Sweden)

    Ye Fang

    Full Text Available Computational modeling of drug binding to proteins is an integral component of direct drug design. Particularly, structure-based virtual screening is often used to perform large-scale modeling of putative associations between small organic molecules and their pharmacologically relevant protein targets. Because of a large number of drug candidates to be evaluated, an accurate and fast docking engine is a critical element of virtual screening. Consequently, highly optimized docking codes are of paramount importance for the effectiveness of virtual screening methods. In this communication, we describe the implementation, tuning and performance characteristics of GeauxDock, a recently developed molecular docking program. GeauxDock is built upon the Monte Carlo algorithm and features a novel scoring function combining physics-based energy terms with statistical and knowledge-based potentials. Developed specifically for heterogeneous computing platforms, the current version of GeauxDock can be deployed on modern, multi-core Central Processing Units (CPUs as well as massively parallel accelerators, Intel Xeon Phi and NVIDIA Graphics Processing Unit (GPU. First, we carried out a thorough performance tuning of the high-level framework and the docking kernel to produce a fast serial code, which was then ported to shared-memory multi-core CPUs yielding a near-ideal scaling. Further, using Xeon Phi gives 1.9× performance improvement over a dual 10-core Xeon CPU, whereas the best GPU accelerator, GeForce GTX 980, achieves a speedup as high as 3.5×. On that account, GeauxDock can take advantage of modern heterogeneous architectures to considerably accelerate structure-based virtual screening applications. GeauxDock is open-sourced and publicly available at www.brylinski.org/geauxdock and https://figshare.com/articles/geauxdock_tar_gz/3205249.

  19. GeauxDock: Accelerating Structure-Based Virtual Screening with Heterogeneous Computing.

    Science.gov (United States)

    Fang, Ye; Ding, Yun; Feinstein, Wei P; Koppelman, David M; Moreno, Juana; Jarrell, Mark; Ramanujam, J; Brylinski, Michal

    2016-01-01

    Computational modeling of drug binding to proteins is an integral component of direct drug design. Particularly, structure-based virtual screening is often used to perform large-scale modeling of putative associations between small organic molecules and their pharmacologically relevant protein targets. Because of a large number of drug candidates to be evaluated, an accurate and fast docking engine is a critical element of virtual screening. Consequently, highly optimized docking codes are of paramount importance for the effectiveness of virtual screening methods. In this communication, we describe the implementation, tuning and performance characteristics of GeauxDock, a recently developed molecular docking program. GeauxDock is built upon the Monte Carlo algorithm and features a novel scoring function combining physics-based energy terms with statistical and knowledge-based potentials. Developed specifically for heterogeneous computing platforms, the current version of GeauxDock can be deployed on modern, multi-core Central Processing Units (CPUs) as well as massively parallel accelerators, Intel Xeon Phi and NVIDIA Graphics Processing Unit (GPU). First, we carried out a thorough performance tuning of the high-level framework and the docking kernel to produce a fast serial code, which was then ported to shared-memory multi-core CPUs yielding a near-ideal scaling. Further, using Xeon Phi gives 1.9× performance improvement over a dual 10-core Xeon CPU, whereas the best GPU accelerator, GeForce GTX 980, achieves a speedup as high as 3.5×. On that account, GeauxDock can take advantage of modern heterogeneous architectures to considerably accelerate structure-based virtual screening applications. GeauxDock is open-sourced and publicly available at www.brylinski.org/geauxdock and https://figshare.com/articles/geauxdock_tar_gz/3205249.

  20. Structural assembly of molecular complexes based on residual dipolar couplings.

    Science.gov (United States)

    Berlin, Konstantin; O'Leary, Dianne P; Fushman, David

    2010-07-07

    We present and evaluate a rigid-body molecular docking method, called PATIDOCK, that relies solely on the three-dimensional structure of the individual components and the experimentally derived residual dipolar couplings (RDCs) for the complex. We show that, given an accurate ab initio predictor of the alignment tensor from a protein structure, it is possible to accurately assemble a protein-protein complex by utilizing the RDCs' sensitivity to molecular shape to guide the docking. The proposed docking method is robust against experimental errors in the RDCs and computationally efficient. We analyze the accuracy and efficiency of this method using experimental or synthetic RDC data for several proteins, as well as synthetic data for a large variety of protein-protein complexes. We also test our method on two protein systems for which the structure of the complex and steric-alignment data are available (Lys48-linked diubiquitin and a complex of ubiquitin and a ubiquitin-associated domain) and analyze the effect of flexible unstructured tails on the outcome of docking. The results demonstrate that it is fundamentally possible to assemble a protein-protein complex solely on the basis of experimental RDC data and the prediction of the alignment tensor from 3D structures. Thus, despite the purely angular nature of RDCs, they can be converted into intermolecular distance/translational constraints. Additionally, we show a method for combining RDCs with other experimental data, such as ambiguous constraints from interface mapping, to further improve structure characterization of protein complexes.

  1. Docking System Design and Self-Assembly Control of Distributed Swarm Flying Robots

    Directory of Open Access Journals (Sweden)

    Hongxing Wei

    2012-11-01

    Full Text Available This paper presents a novel docking system design and the distributed self‐assembly control strategy for a Distributed Swarm Flying Robot (DSFR. The DSFR is a swarm robot comprising many identical robot modules that are able to move on the ground, dock with each other and fly coordinately once self‐assembled into a robotic structure. A generalized adjacency matrix method is proposed to describe the configurations of robotic structures. Based on the docking system and the adjacency matrix, experiments are performed to demonstrate and verify the self‐assembly control strategy.

  2. Small-molecule library screening by docking with PyRx.

    Science.gov (United States)

    Dallakyan, Sargis; Olson, Arthur J

    2015-01-01

    Virtual molecular screening is used to dock small-molecule libraries to a macromolecule in order to find lead compounds with desired biological function. This in silico method is well known for its application in computer-aided drug design. This chapter describes how to perform small-molecule virtual screening by docking with PyRx, which is open-source software with an intuitive user interface that runs on all major operating systems (Linux, Windows, and Mac OS). Specific steps for using PyRx, as well as considerations for data preparation, docking, and data analysis, are also described.

  3. Result of Rendezvous Docking Experiment of ETS.35zw .5zw .25mmVII

    Science.gov (United States)

    Kawano, Isao; Mokuno, Masaaki; Suzuki, Takashi; Koyama, Hiroshi; Kunugi, Makoto

    ETS VII is a test satellite to perform in-orbit demonstration of autonomous rendezvous docking (RVD) technology, which will be necessary for advanced space activities in the early 21st century. ETS VII performed three RVD experiment flights, and verified all technical items. ETS VII demonstrated first autonomous RVD between unmanned vehicles, and remote piloted rendezvous flight position accuracy at docking was about 1cm, and acceleration was less than 1.5mG (low impact docking). In the second RVD experiment flight, ETS VII detected attitude anomaly and executed disable abort for safety insurance. We present the results and evaluation of three RVD experiment flights in this paper.

  4. DNA gridiron nanostructures based on four-arm junctions.

    Science.gov (United States)

    Han, Dongran; Pal, Suchetan; Yang, Yang; Jiang, Shuoxing; Nangreave, Jeanette; Liu, Yan; Yan, Hao

    2013-03-22

    Engineering wireframe architectures and scaffolds of increasing complexity is one of the important challenges in nanotechnology. We present a design strategy to create gridiron-like DNA structures. A series of four-arm junctions are used as vertices within a network of double-helical DNA fragments. Deliberate distortion of the junctions from their most relaxed conformations ensures that a scaffold strand can traverse through individual vertices in multiple directions. DNA gridirons were assembled, ranging from two-dimensional arrays with reconfigurability to multilayer and three-dimensional structures and curved objects.

  5. Spectroscopic and molecular docking studies of binding interaction of gefitinib, lapatinib and sunitinib with bovine serum albumin (BSA).

    Science.gov (United States)

    Shen, Guo-Feng; Liu, Ting-Ting; Wang, Qi; Jiang, Min; Shi, Jie-Hua

    2015-12-01

    The binding interactions of three kinds of tyrosine kinase inhibitors (TKIs), such as gefitinib, lapatinib and sunitinib, with bovine serum albumin (BSA) were studied using ultraviolet spectrophotometry, fluorescence spectroscopy, circular dichroism (CD), Fourier transform infrared spectroscopy (FT-IR) and molecular docking methods. The experimental results showed that the intrinsic fluorescence quenching of BSA induced by the three TKIs resulted from the formation of stable TKIs-BSA complexes through the binding interaction of TKIs with BSA. The stoichiometry of three stable TKIs-BSA complexes was 1:1 and the binding constants (Kb) of the three TKIs-BSA complexes were in the order of 10(4)M(-1) at 310 K, indicating that there was a strong binding interaction of the three TKIs with BSA. Based on the analysis of the signs and magnitudes of the free energy change (ΔG(0)), enthalpic change (ΔH(0)) and entropic change (ΔS(0)) in the binding process, it can be deduced that the binding process of the three TKIs with BSA was spontaneous and enthalpy-driven process, and the main interaction forces between the three TKIs and BSA were van der Waals force and hydrogen bonding interaction. Moreover, from the results of CD, FT-IR and molecular docking, it can be concluded that there was a significant difference between the three TKIs in the binding site on BSA, lapatinib was located on site II (m) of BSA while gefitinib and sunitinib were bound on site I of BSA, and there were some changes in the BSA conformation when binding three TKIs to BSA but BSA still retains its secondary structure α-helicity.

  6. MiniSAR composite gimbal arm development.

    Energy Technology Data Exchange (ETDEWEB)

    Klarer, Paul Richard; Winscott, Mark (Orion International, Albuquerque, NM)

    2005-01-01

    An exploratory effort in the application of carbon epoxy composite structural materials to a multi-axis gimbal arm design is described. An existing design in aluminum was used as a baseline for a functionally equivalent redesigned outer gimbal arm using a carbon epoxy composite material. The existing arm was analyzed using finite element techniques to characterize performance in terms of strength, stiffness, and weight. A new design was virtually prototyped. using the same tools to produce a design with similar stiffness and strength, but reduced overall weight, than the original arm. The new design was prototyped using Rapid Prototyping technology, which was subsequently used to produce molds for fabricating the carbon epoxy composite parts. The design tools, process, and results are discussed.

  7. Ablation of the microglial protein DOCK2 reduces amyloid burden in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Cimino, Patrick J; Yang, Yue; Li, Xianwu; Hemingway, Jake F; Cherne, Makenzie K; Khademi, Shawn B; Fukui, Yoshinori; Montine, Kathleen S; Montine, Thomas J; Keene, C Dirk

    2013-04-01

    Alzheimer's disease (AD) neuropathology is characterized by innate immune activation primarily through prostaglandin E2 (PGE2) signaling. Dedicator of cytokinesis 2 (DOCK2) is a guanyl nucleotide exchange factor expressed exclusively in microglia in the brain and is regulated by PGE2 receptor EP2. DOCK2 modulates microglia cytokine secretion, phagocytosis, and paracrine neurotoxicity. EP2 ablation in experimental AD results in reduced oxidative damage and amyloid beta (Aβ) burden. This discovery led us to hypothesize that genetic ablation of DOCK2 would replicate the anti-Aβ effects of loss of EP2 in experimental AD. To test this hypothesis, we crossed mice that lacked DOCK2 (DOCK2-/-), were hemizygous for DOCK2 (DOCK2+/-), or that expressed two DOCK2 genes (DOCK2+/+) with APPswe-PS1Δe9 mice (a model of AD). While we found no DOCK2-dependent differences in cortex or in hippocampal microglia density or morphology in APPswe-PS1Δe9 mice, cerebral cortical and hippocampal Aβ plaque area and size were significantly reduced in 10-month-old APPswe-PS1Δe9/DOCK2-/- mice compared with APPswe-PS1Δe9/DOCK2+/+ controls. DOCK2 hemizygous APPswe-PS1Δe9 mice had intermediate Aβ plaque levels. Interestingly, soluble Aβ42 was not significantly different among the three genotypes, suggesting the effects were mediated specifically in fibrillar Aβ. In combination with earlier cell culture results, our in vivo results presented here suggest DOCK2 contributes to Aβ plaque burden via regulation of microglial innate immune function and may represent a novel therapeutic target for AD.

  8. The long arms of anencephaly: A refutation.

    Science.gov (United States)

    Barr, Mason

    2009-08-01

    A paper published in 1925 reported that human fetuses with anencephaly have arms that are longer than normal. This finding was accepted as true through the early 1990s. An analysis of body dimensions done in 1996 and enlarged and updated here shows that the arms of human fetuses with anencephaly are appropriate for gestational age and normal in proportion to their leg lengths. A subtle difference in measurement technique was found to explain the discordant findings.

  9. The Geometry of the Galaxy's Spiral Arms

    Science.gov (United States)

    Steiman-Cameron, Thomas Y.; Wolfire, M.; Hollenbach, D.

    2008-05-01

    We present a new model for the spiral structure of the Milky Way based upon an analysis of the essentially all-sky spectral data obtained by the Far Infrared Absolute Spectrophotometer (FIRAS) instrument of the Cosmic Background Explorer (COBE) satellite. The model provides the volume emissivities of the [C II] 128 µm and [N II] 205 µm lines, as a function of position within the Galaxy. These lines are important coolants of the interstellar medium and strong tracers of the spiral structure. Despite decades of work, there is still no full agreement on the number of spiral arms in the Milky Way, much less the details of their geometry. Motivated, in part, by this fact, we conducted a systematic search for 2-arm, 3-arm, and 4-arm models that maximize agreement with the COBE data. We find that only a four-arm model, with arms defined by logarithmic spiral forms and pitch angles ranging from 13.5 to 15.6 degrees, is consistent with the observations. The arms are neither evenly spaced nor identical in form. The resultant volume emissivity models for C+ and N+, when convolved with the FIRAS beam and integrated over the Galaxy, reproduce the COBE [C II] 128 µm and [N II] 205 µm intensity maps extremely well. We also examine all models for the Galaxy's spiral structure that have been proposed over the past half century in the context of the same COBE observations. A significant fraction of these models, including many recent ones, appear to be incompatible with the data. However, several four-arm models from the literature are consistent with the COBE observations.

  10. Regulation of flexible arms under gravity

    Energy Technology Data Exchange (ETDEWEB)

    De Luca, A. [Univ. di Roma, Rome (Italy). Dipt. di Informatica e Sistemistica; Siciliano, B. [Univ. di Napoli Federico, Napoli (Italy). Dipt. di Informatica e Sistemistica

    1993-08-01

    A simple controller is presented for the regulation problem of robot arms with flexible links under gravity. It consists of a joint PD feedback plus a constant feedforward. Global asymptotic stability of the reference equilibrium state is shown under a structural assumption about link elasticity and a mild condition on the proportional gain. The result holds also in the absence of internal damping of the flexible arm. A numerical case study is presented.

  11. Screening and docking studies of natural phenolic inhibitors of carbonic anhydrase Ⅱ

    Institute of Scientific and Technical Information of China (English)

    HUANG Huo-Qiang; PAN Xu-Lin; JI Chang-Jiu; ZENG Guang-Zhi; JIANG Li-Hua; FU Xiang; LIU Ji-Kai; HAO Xiao-Jiang; ZHANG Ying-Jun; TAN Ning-Hua

    2009-01-01

    Carbonic anhydrase Ⅱ (CAⅡ) is an Important enzyme complex with Zn2+, which is involved in many physiological and pathological processes, such as calcification, glaucoma and tumorigenicity. In order to search for novel inhibitors of CA Ⅱ, inhibition assay of carbonic anhydrase Ⅱ was performed, by which seven natural phenolic compounds, including four phenolics (grifolln, 4-O-methyl-grifolic acid, grifolic acid, and isovanillic acid) and three flavones (eriodictyol, quercetin and puerin A), showed in-hibitory activities against CAⅡ with IC50s in the range of 6.37-71.73 μmol/L. Grifolic acid is the most active one with IC50 of 6.37 μmol/L. These seven phenolic compounds were proved to be novel natural carbonic anhydrase Ⅱ inhibitors, which were obtained in flexible docking study with GOLD 3.0 soft-ware. Results indicated that the aliphatic chain and polar groups of hydroxyl and carboxyl are impor-tant to their inhibitory activities, providing a new insight into study on CA Ⅱ potent inhibitors.

  12. Screening and docking studies of natural phenolic inhibitors of carbonic anhydrase Ⅱ

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Carbonic anhydrase Ⅱ (CAⅡ) is an important enzyme complex with Zn2+,which is involved in many physiological and pathological processes, such as calcification, glaucoma and tumorigenicity. In order to search for novel inhibitors of CAⅡ, inhibition assay of carbonic anhydrase Ⅱ was performed, by which seven natural phenolic compounds, including four phenolics (grifolin, 4-O-methyl-grifolic acid, grifolic acid, and isovanillic acid) and three flavones (eriodictyol, quercetin and puerin A), showed in-hibitory activities against CAⅡ with IC50s in the range of 6.37-71.73 μmol/L. Grifolic acid is the most active one with IC50 of 6.37 μmol/L. These seven phenolic compounds were proved to be novel natural carbonic anhydrase Ⅱ inhibitors, which were obtained in flexible docking study with GOLD 3.0 soft-ware. Results indicated that the aliphatic chain and polar groups of hydroxyl and carboxyl are impor-tant to their inhibitory activities, providing a new insight into study on CA Ⅱ potent inhibitors.

  13. Identification of New Nonsteroidal RORα Ligands; Related Structure-Activity Relationships and Docking Studies.

    Science.gov (United States)

    Dubernet, Mathieu; Duguet, Nicolas; Colliandre, Lionel; Berini, Christophe; Helleboid, Stéphane; Bourotte, Marilyne; Daillet, Matthieu; Maingot, Lucie; Daix, Sébastien; Delhomel, Jean-François; Morin-Allory, Luc; Routier, Sylvain; Walczak, Robert

    2013-06-13

    A high throughput screen was developed to identify novel, nonsteroidal RORα agonists. Among the validated hit compounds, the 4-(4-(benzyloxy)phenyl)-5-carbonyl-2-oxo-1,2,3,4-tetrahydropyrimidine scaffold was the most prominent. Among the numerous analogues tested, compounds 8 and 9 showed the highest activity. Key structure-activity relationships (SAR) were established, where benzyl and urea moieties were both identified as very important elements to maintain the activity. Most notably, the SAR were consistent with the binding mode of the compound 8 (S-isomer) in the RORα docking model that was developed in this program. As predicted by the model, the urea moiety is engaged in the formation of key hydrogen bonds with the backbone of Tyr380 and Asp382. The benzyl group is located in a wide hydrophobic pocket. The structural relationships reported in this letter will help in further optimization of this compound series and will provide novel synthetic probes helpful for elucidation of complex RORα physiopathology.

  14. pK(a) based protonation states and microspecies for protein-ligand docking.

    Science.gov (United States)

    ten Brink, Tim; Exner, Thomas E

    2010-11-01

    In this paper we present our reworked approach to generate ligand protonation states with our structure preparation tool SPORES (Structure PrOtonation and REcognition System). SPORES can be used for the preprocessing of proteins and protein-ligand complexes as e.g. taken from the Protein Data Bank as well as for the setup of 3D ligand databases. It automatically assigns atom and bond types, generates different protonation, tautomeric states as well as different stereoisomers. In the revised version, pKa calculations with the ChemAxon software MARVIN are used either to determine the likeliness of a combinatorial generated protonation state or to determine the titrable atoms used in the combinatorial approach. Additionally, the MARVIN software is used to predict microspecies distributions of ligand molecules. Docking studies were performed with our recently introduced program PLANTS (Protein-Ligand ANT System) on all protomers resulting from the three different selection methods for the well established CCDC/ASTEX clean data set demonstrating the usefulness of especially the latter approach.

  15. Synthesis, kinetic mechanism and docking studies of vanillin derivatives as inhibitors of mushroom tyrosinase.

    Science.gov (United States)

    Ashraf, Zaman; Rafiq, Muhammad; Seo, Sung-Yum; Babar, Mustafeez Mujtaba; Zaidi, Najam-us-Sahar Sadaf

    2015-09-01

    The purpose of the present study was to discover the extent of contribution to antityrosinase activity by adding hydroxy substituted benzoic acid, cinnamic acid and piperazine residues to vanillin. The study showed the transformation of vanillin into esters as shown in (4a-4d), (6a-6b), and (8a-8b). In addition, the relationship between structures of these esters and their mushroom tyrosinase inhibitory activity was explored. The kinetics of inhibition on mushroom tyrosinase by these esters was also investigated. It was found that hydroxyl substituted benzoic acid derivatives were weak inhibitors; however hydroxy or chloro substituted cinnamic acid and piperazine substituted derivatives were able to induce significant tyrosinase inhibition. The mushroom tyrosinase (PDBID 2ZWE) was docked with synthesized vanillin derivatives and their calculated binding energies were compared with experimental IC50 values which provided positive correlation. The most potent derivative 2-(4-formyl-2-methoxyphenoxy)-2-oxoethyl (2E)-3-(4-hydroxyphenyl)prop-2-enoate (6a) possesses hydroxy substituted cinnamic acid scaffold having IC50 value 16.13 μM with binding energy of -7.2 kcal/mol. The tyrosinase inhibitory activity of (6a) is comparable with standard kojic acid. Kinetic analysis indicated that compound 6a was mixed-type tyrosinase inhibitor with inhibition constant values Ki (13 μM) and Ki' (53 μM) and formed reversible enzyme inhibitor complex. The active vanillin analog (6a) was devoid of toxic effects as shown in cytotoxic studies.

  16. ARM assembly language with hardware experiments

    CERN Document Server

    Elahi, Ata

    2015-01-01

    This book provides a hands-on approach to learning ARM assembly language with the use of a TI microcontroller. The book starts with an introduction to computer architecture and then discusses number systems and digital logic. The text covers ARM Assembly Language, ARM Cortex Architecture and its components, and Hardware Experiments using TILM3S1968. Written for those interested in learning embedded programming using an ARM Microcontroller. ·         Introduces number systems and signal transmission methods   ·         Reviews logic gates, registers, multiplexers, decoders and memory   ·         Provides an overview and examples of ARM instruction set   ·         Uses using Keil development tools for writing and debugging ARM assembly language Programs   ·         Hardware experiments using a Mbed NXP LPC1768 microcontroller; including General Purpose Input/Output (GPIO) configuration, real time clock configuration, binary input to 7-segment display, creating ...

  17. Membrane docking geometry of GRP1 PH domain bound to a target lipid bilayer: an EPR site-directed spin-labeling and relaxation study.

    Directory of Open Access Journals (Sweden)

    Huai-Chun Chen

    Full Text Available The second messenger lipid PIP(3 (phosphatidylinositol-3,4,5-trisphosphate is generated by the lipid kinase PI3K (phosphoinositide-3-kinase in the inner leaflet of the plasma membrane, where it regulates a broad array of cell processes by recruiting multiple signaling proteins containing PIP(3-specific pleckstrin homology (PH domains to the membrane surface. Despite the broad importance of PIP(3-specific PH domains, the membrane docking geometry of a PH domain bound to its target PIP(3 lipid on a bilayer surface has not yet been experimentally determined. The present study employs EPR site-directed spin labeling and relaxation methods to elucidate the membrane docking geometry of GRP1 PH domain bound to bilayer-embedded PIP(3. The model target bilayer contains the neutral background lipid PC and both essential targeting lipids: (i PIP(3 target lipid that provides specificity and affinity, and (ii PS facilitator lipid that enhances the PIP(3 on-rate via an electrostatic search mechanism. The EPR approach measures membrane depth parameters for 18 function-retaining spin labels coupled to the PH domain, and for calibration spin labels coupled to phospholipids. The resulting depth parameters, together with the known high resolution structure of the co-complex between GRP1 PH domain and the PIP(3 headgroup, provide sufficient constraints to define an optimized, self-consistent membrane docking geometry. In this optimized geometry the PH domain engulfs the PIP(3 headgroup with minimal bilayer penetration, yielding the shallowest membrane position yet described for a lipid binding domain. This binding interaction displaces the PIP(3 headgroup from its lowest energy position and orientation in the bilayer, but the headgroup remains within its energetically accessible depth and angular ranges. Finally, the optimized docking geometry explains previous biophysical findings including mutations observed to disrupt membrane binding, and the rapid lateral

  18. Discovery of high affinity ligands for β2-adrenergic receptor through pharmacophore-based high-throughput virtual screening and docking.

    Science.gov (United States)

    Yakar, Ruya; Akten, Ebru Demet

    2014-09-01

    Novel high affinity compounds for human β2-adrenergic receptor (β2-AR) were searched among the clean drug-like subset of ZINC database consisting of 9,928,465 molecules that satisfy the Lipinski's rule of five. The screening protocol consisted of a high-throughput pharmacophore screening followed by an extensive amount of docking and rescoring. The pharmacophore model was composed of key features shared by all five inactive states of β2-AR in complex with inverse agonists and antagonists. To test the discriminatory power of the pharmacophore model, a small-scale screening was initially performed on a database consisting of 117 compounds of which 53 antagonists were taken as active inhibitors and 64 agonists as inactive inhibitors. Accordingly, 7.3% of the ZINC database subset (729,413 compounds) satisfied the pharmacophore requirements, along with 44 antagonists and 17 agonists. Afterwards, all these hit compounds were docked to the inactive apo form of the receptor using various docking and scoring protocols. Following each docking experiment, the best pose was further evaluated based on the existence of key residues for antagonist binding in its vicinity. After final evaluations based on the human intestinal absorption (HIA) and the blood brain barrier (BBB) penetration properties, 62 hit compounds have been clustered based on their structural similarity and as a result four scaffolds were revealed. Two of these scaffolds were also observed in three high affinity compounds with experimentally known Ki values. Moreover, novel chemical compounds with distinct structures have been determined as potential β2-AR drug candidates.

  19. Interaction of bovine serum albumin with a psychotropic drug alprazolam: Physicochemical, photophysical and molecular docking studies

    Energy Technology Data Exchange (ETDEWEB)

    Sarkar, Moumita; Paul, Shiv Shankar; Mukherjea, Kalyan K., E-mail: k_mukherjea@yahoo.com

    2013-10-15

    The interaction between alprazolam (Alp) and bovine serum albumin (BSA) has been investigated under physiological conditions by UV–vis, steady state as well as time-resolved fluorescence, circular dichroism (CD) spectroscopic and molecular docking studies. The binding constant K of Alp to BSA was found to be 1.8×10{sup 5} L mol{sup −1} from absorption data. Fluorometric studies suggested the formation of the Alp–BSA complex, while time-resolved fluorescence studies showed that the binding of Alp by BSA was mainly static and the effective rate constant is found to be 2.33×10{sup 13} L mol{sup −1} s{sup −1}. According to the modified Stern–Volmer equation, the Stern–Volmer quenching constants (K{sub SV}) between Alp and BSA at four different temperatures 295, 303, 308, 313 K were obtained to be 1.19×10{sup 5}, 1.05×10{sup 5}, 0.99×10{sup 5} and 0.90×10{sup 5} L mol{sup −1}, respectively. The change in enthalpy (ΔH) and entropy (ΔS) were calculated to be −11.66 and 57.64 J mol{sup −1} K{sup −1}, respectively, indicating that the interaction was hydrophobic in nature. Site marker competitive experiments suggested that the binding of Alp to BSA primarily took place in sub-domain IIA, whereas the binding distance (r) between Alp and the tryptophan residue of BSA was obtained to be 1.87 nm by Förster's theory of non-radiative energy transfer. The conformational studies by CD spectroscopy showed that the presence of Alp decreased the α-helical content of BSA and induced the unfolding of the polypeptide of the protein. The change in conformation was also supported by excitation–emission matrix spectroscopy (EEMS) studies. The molecular docking experiment supports the above results and effectively proves the binding of Alp to BSA. -- Highlights: • Alprazolam: a benzodiazepine drug with anxiolytic and anticonvulsant properties. • Alprazolam induces conformational change on the native as well as urea denatured BSA. • Alprazolam may

  20. Boring crustaceans damage polystyrene floats under docks polluting marine waters with microplastic.

    Science.gov (United States)

    Davidson, Timothy M

    2012-09-01

    Boring isopods damage expanded polystyrene floats under docks and, in the process, expel copious numbers of microplastic particles. This paper describes the impacts of boring isopods in aquaculture facilities and docks, quantifies and discusses the implications of these microplastics, and tests if an alternate foam type prevents boring. Floats from aquaculture facilities and docks were heavily damaged by thousands of isopods and their burrows. Multiple sites in Asia, Australia, Panama, and the USA exhibited evidence of isopod damage. One isopod creates thousands of microplastic particles when excavating a burrow; colonies can expel millions of particles. Microplastics similar in size to these particles may facilitate the spread of non-native species or be ingested by organisms causing physical or toxicological harm. Extruded polystyrene inhibited boring, suggesting this foam may prevent damage in the field. These results reveal boring isopods cause widespread damage to docks and are a novel source of microplastic pollution.