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Sample records for westridge dock transfer

  1. Concepts to Automate Fluid Transfer Capability of Low Impact Docking System (LIDS)

    Science.gov (United States)

    Miernik, Janie H.; Lukens, Scott; Robertson, Jeff

    2005-01-01

    The capability to transfer mass between spacecraft is necessary for many mission scenarios. Docking and berthing operations have enabled fluid, electrical, crew and equipment transfers to some degree on all manned space operations since the Gemini program. The Apollo program performed some sophisticated docking maneuvers to land men on the moon and return them safely to Earth. These programs primarily transferred crew, equipment, and pressurized atmosphere between docked spacecraft. The International Space Station (ISS) U.S. modules are connected by Common Berthing Mechanism (CBM) portals. They provide many feed-through ports for electrical, and fluid transfer between modules, as well as a large diameter crew and equipment tunnel. Fluid and electrical jumpers are manually installed after the CBM sealing surfaces have been securely mated to maintain the pressurized cabin environment. CBM berthing and subsequent fluid transfer capability requires a lengthy manual process involving an active interface that mates with a passive half. The Androgynous Peripheral Attach System (MAS) a Russian technology that docked the Russian Zarya module to Unity, or Node 1, is a more complex system that also is capable of fuel transfer, enabling refueling of the Russian re-boost engines on ISS. For several years, a Low Impact Docking System (LIDS) has been under development at Johnson Space Center (JSC). This docking technology has a requirement to be androgynous in order to allow the fabrication of a single configuration that can dock with all other LIDS units. It is desired to make electrical and fluid coupling mating an automated process to enable routine docking and undocking operations to support future exploration missions. It is envisioned that modular design and vehicle assembly will require an efficient LIDS for fuel, electrical, crew, and equipment transfer. Marshall Space Flight Center (MSFC) has joined the LIDS development effort and plans to employ fluid transfer concepts

  2. Acromioclavicular joint reconstruction with coracoacromial ligament transfer using the docking technique

    Directory of Open Access Journals (Sweden)

    Gobezie Reuben

    2009-01-01

    Full Text Available Abstract Background Symptomatic Acromioclavicular (AC dislocations have historically been surgically treated with Coracoclavicular (CC ligament reconstruction with transfer of the Coracoacromial (CA ligament. Tensioning the CA ligament is the key to success. Methods Seventeen patients with chronic, symptomatic Type III AC joint or acute Type IV and V injuries were treated surgically. The distal clavicle was resected and stabilized with CC ligament reconstruction using the CA ligament. The CA ligament was passed into the medullary canal and tensioned, using a modified 'docking' technique. Average follow-up was 29 months (range 12–57. Results Postoperative ASES and pain significantly improved in all patients (p = 0.001. Radiographically, 16 (94% maintained reduction, and only 1 (6% had a recurrent dislocation when he returned to karate 3 months postoperatively. His ultimate clinical outcome was excellent. Conclusion The docking procedure allows for tensioning of the transferred CA ligament and healing of the ligament in an intramedullary bone tunnel. Excellent clinical results were achieved, decreasing the risk of recurrent distal clavicle instability.

  3. 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.

  4. Photophysics of a proton transfer phototautomer within biological confinement of a protein: Spectroscopic and molecular docking studies

    Energy Technology Data Exchange (ETDEWEB)

    Paul, Bijan K., E-mail: bijan.paul.chem.cu@gmail.com; Guchhait, Nikhil, E-mail: nguchhait@yahoo.com

    2014-09-15

    The present work demonstrates the effect of biological confinement on the photophysics of a proton transfer phototautomer viz., 2-hydroxy-1-naphthaldehyde (HN21). HN21 is a potential candidate exhibiting excited-state intramolecular proton transfer (ESIPT) reaction and thereby generating the phototautomer (i.e., proton transferred keto form) in the excited-state. The ESIPT photophysics of the probe (HN21) is found to be remarkably modified within the confined bio-environment of a model transport protein Bovine Serum Albumin (BSA). Such considerable modification of the ESIPT photophysics of the probe has been exploited to determine the probe–protein binding strength (binding constant, K(±10%)=1.23×10{sup 4} M{sup −1}). The probe–protein binding process is found to be thermodynamically feasible (ΔG=−24.25 kJ mol{sup −1}). The present work also delves into evaluation of the probable binding location of the probe (HN21) within the biomacromolecular assembly of the protein by blind docking simulation technique, which reveals that HN21 favorably binds to the hydrophobic subdomain IIIA of BSA. Circular dichroism (CD) spectroscopy delineates the effect of probe binding on the protein secondary structure in terms of decrease of α-helical content of BSA with increasing probe concentration. Apart from this, excitation–emission matrix fluorescence technique is found to hint at the effect on protein tertiary structure upon binding to the probe. The modulated dynamics of the proton transfer phototautomer of HN21 within the biological confinement is investigated in this context by time-resolved fluorescence decay measurements. The present work also accentuates the mutually corroborating data found from experimental and computational studies. - Highlights: • Remarkable modification of ESIPT emission of HN21 in protein is explored. • Probe–protein binding efficiency is evaluated from fluorescence spectral data. • Binding to the probe accompanies perturbation

  5. 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

  6. Low Impact Docking System (LIDS)

    Science.gov (United States)

    LaBauve, Tobie E.

    2009-01-01

    Since 1996, NASA has been developing a docking system that will simplify operations and reduce risks associated with mating spacecraft. This effort has focused on developing and testing an original, reconfigurable, active, closed-loop, force-feedback controlled docking system using modern technologies. The primary objective of this effort has been to design a docking interface that is tunable to the unique performance requirements for all types of mating operations (i.e. docking and berthing, autonomous and piloted rendezvous, and in-space assembly of vehicles, modules and structures). The docking system must also support the transfer of crew, cargo, power, fluid, and data. As a result of the past 10 years of docking system advancement, the Low Impact Docking System or LIDS was developed. The current LIDS design incorporates the lessons learned and development experiences from both previous and existing docking systems. LIDS feasibility was established through multiple iterations of prototype hardware development and testing. Benefits of LIDS include safe, low impact mating operations, more effective and flexible mission implementation with an anytime/anywhere mating capability, system level redundancy, and a more affordable and sustainable mission architecture with reduced mission and life cycle costs. In 1996 the LIDS project, then known as the Advanced Docking Berthing System (ADBS) project, launched a four year developmental period. At the end of the four years, the team had built a prototype of the soft-capture hardware and verified the control system that will be used to control the soft-capture system. In 2001, the LIDS team was tasked to work with the X- 38 Crew Return Vehicle (CRV) project and build its first Engineering Development Unit (EDU).

  7. Effects of wood preservative leachates from docks

    Energy Technology Data Exchange (ETDEWEB)

    Wendt, P.H.; Van Dolah, R.F.; Bobo, M.Y.; Mathews, T.D. [South Carolina Marine Resources Research Inst., Charleston, SC (United States)

    1994-12-31

    Recent evidence indicates that the wood preservative commonly used in dock pilings (chromated copper arsenate or CCA) is highly toxic to several estuarine organisms in laboratory experiments. Increasing demand for residential docks prompted a field study intended to complement these earlier laboratory investigations. Objectives of the study were to: (1) examine concentrations of Cu, Cr, and As in sediments and oysters from intertidal locations in several creeks with and without high densities of docks; (2) examine the bioaccumulation of wood preservative leachates by laboratory-reared oysters transferred to field sites near and distant from newly constructed docks; and (3) investigate the acute toxicity of wood preservative leachates for several species of estuarine fishes and invertebrates exposed to these compounds in the field. Preliminary results indicate that sediment concentrations of all three metals were well below ER-L levels reported by Long and Morgan at all but one dock site. In an ancillary study, 24h LC{sub 50} bioassays were performed using rotifers (Brachionus plicatilis) which were exposed to pore water from sediments in creeks with and without docks. Toxicities of bulk sediments from the same sites were examined using Microtox which measures decreases in bioluminescence of marine bacteria (Photobacterium phosphoreum) as a function of sediment concentration. Neither the rotifer nor the Microtox bioassays showed any significant differences in toxicity between creeks with and without docks.

  8. Spectroscopic and molecular docking studies on the charge transfer complex of bovine serum albumin with quinone in aqueous medium and its influence on the ligand binding property of the protein

    Science.gov (United States)

    Satheshkumar, Angupillai; Elango, Kuppanagounder P.

    2014-09-01

    The spectral techniques such as UV-Vis, 1H NMR and fluorescence and electrochemical experiments have been employed to investigate the interaction between 2-methoxy-3,5,6-trichloro-1,4-benzoquinone (MQ; a water soluble quinone) and bovine serum albumin (BSA) in aqueous medium. The fluorescence of BSA was quenched by MQ via formation of a 1:1 BSA-MQ charge transfer adduct with a formation constant of 3.3 × 108 L mol-1. Based on the Forster’s theory the binding distance between them is calculated as 2.65 nm indicating high probability of binding. For the first time, influence of quinone on the binding property of various types of ligands such as aspirin, ascorbic acid, nicotinimide and sodium stearate has also been investigated. The results indicated that the strong and spontaneous binding existing between BSA and MQ, decreased the intensity of binding of these ligands with BSA. Since Tryptophan (Trp) is the basic residue present in BSA, a comparison between binding property of Trp-MQ adduct with that of BSA-MQ with these ligands has also been attempted. 1H NMR titration study indicated that the Trp forms a charge transfer complex with MQ, which reduces the interaction of Trp with the ligands. Molecular docking study supported the fact that the quinone interacts with the Trp212 unit of the BSA and the free energy change of binding (ΔG) for the BSA-MQ complex was found to be -46 kJ mol-1, which is comparable to our experimental free energy of binding (-49 kJ mol-1) obtained from fluorescence study.

  9. Spectroscopic and molecular docking studies on the charge transfer complex of bovine serum albumin with quinone in aqueous medium and its influence on the ligand binding property of the protein.

    Science.gov (United States)

    Satheshkumar, Angupillai; Elango, Kuppanagounder P

    2014-09-15

    The spectral techniques such as UV-Vis, (1)H NMR and fluorescence and electrochemical experiments have been employed to investigate the interaction between 2-methoxy-3,5,6-trichloro-1,4-benzoquinone (MQ; a water soluble quinone) and bovine serum albumin (BSA) in aqueous medium. The fluorescence of BSA was quenched by MQ via formation of a 1:1 BSA-MQ charge transfer adduct with a formation constant of 3.3×10(8) L mol(-1). Based on the Forster's theory the binding distance between them is calculated as 2.65 nm indicating high probability of binding. For the first time, influence of quinone on the binding property of various types of ligands such as aspirin, ascorbic acid, nicotinimide and sodium stearate has also been investigated. The results indicated that the strong and spontaneous binding existing between BSA and MQ, decreased the intensity of binding of these ligands with BSA. Since Tryptophan (Trp) is the basic residue present in BSA, a comparison between binding property of Trp-MQ adduct with that of BSA-MQ with these ligands has also been attempted. 1H NMR titration study indicated that the Trp forms a charge transfer complex with MQ, which reduces the interaction of Trp with the ligands. Molecular docking study supported the fact that the quinone interacts with the Trp212 unit of the BSA and the free energy change of binding (ΔG) for the BSA-MQ complex was found to be -46 kJ mol(-1), which is comparable to our experimental free energy of binding (-49 kJ mol(-1)) obtained from fluorescence study. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Spacecraft rendezvous and docking

    DEFF Research Database (Denmark)

    Jørgensen, John Leif

    1999-01-01

    The phenomenons and problems encountered when a rendezvous manoeuvre, 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 analysed. So far, all solutions that has been brought into realization has...... 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...... relative pose information to assist the human operator during the docking phase. The closed loop and operator assistance performance of the system have been assessed using a test bench including human operator, navigation module and high fidelity visualization module. The tests performed verified...

  11. Highly Flexible Protein-Peptide Docking Using CABS-Dock.

    Science.gov (United States)

    Ciemny, Maciej Paweł; Kurcinski, Mateusz; Kozak, Konrad Jakub; Kolinski, Andrzej; Kmiecik, Sebastian

    2017-01-01

    Protein-peptide molecular docking is a difficult modeling problem. It is even more challenging when significant conformational changes that may occur during the binding process need to be predicted. In this chapter, we demonstrate the capabilities and features of the CABS-dock server for flexible protein-peptide docking. CABS-dock allows highly efficient modeling of full peptide flexibility and significant flexibility of a protein receptor. During CABS-dock docking, the peptide folding and binding process is explicitly simulated and no information about the peptide binding site or its structure is used. This chapter presents a successful CABS-dock use for docking a potentially therapeutic peptide to a protein target. Moreover, simulation contact maps, a new CABS-dock feature, are described and applied to the docking test case. Finally, a tutorial for running CABS-dock from the command line or command line scripts is provided. The CABS-dock web server is available from http://biocomp.chem.uw.edu.pl/CABSdock/ .

  12. Magnetic docking aid for orbiter to ISS docking

    Science.gov (United States)

    Schneider, William C.; Nagy, Kornel; Schliesing, John A.

    1996-01-01

    The present docking system for the Orbiter uses mechanical capture latches that are actuated by contact forces. The forces are generated when the two approaching masses collide at the docking mechanism. There is always a trade-off between having high enough momentum to effect capture and low enough momentum to avoid structural overload or unacceptable angular displacements. The use of the present docking system includes a contact thrusting maneuver that causes high docking loads to be included into Space Station. A magnetic docking aid has been developed to reduce the load s during docking. The magnetic docking aid is comprised of two extendible booms that are attached adjacent to the docking structure with electromagnets attached on the end of the boom. On the mating vehicle, two steel plates are attached. As the Orbiter approaches Space Station, the booms are extended, and the magnets attach to the actuated (without thrusting), by slowly driving the extendible booms to the stowed position, thus reacting the load into the booms. This results in a docking event that has lower loads induced into Space Station structure. This method also greatly simplifies the Station berthing tasks, since the Shuttle Remote Manipulation System (SRMS) arm need only place the element to be berthed on the magnets (no load required), rather than firing the Reaction Control System (RCS) jets to provide the required force for capture latch actuation. The Magnetic Docking Aid was development testing on a six degree-of-freedom (6 DOF) system at JSC.

  13. Cell-Dock: high-performance protein-protein docking.

    Science.gov (United States)

    Pons, Carles; Jiménez-González, Daniel; González-Álvarez, Cecilia; Servat, Harald; Cabrera-Benítez, Daniel; Aguilar, Xavier; Fernández-Recio, Juan

    2012-09-15

    The application of docking to large-scale experiments or the explicit treatment of protein flexibility are part of the new challenges in structural bioinformatics that will require large computer resources and more efficient algorithms. Highly optimized fast Fourier transform (FFT) approaches are broadly used in docking programs but their optimal code implementation leaves hardware acceleration as the only option to significantly reduce the computational cost of these tools. In this work we present Cell-Dock, an FFT-based docking algorithm adapted to the Cell BE processor. We show that Cell-Dock runs faster than FTDock with maximum speedups of above 200×, while achieving results of similar quality. The source code is released under GNU General Public License version 2 and can be downloaded from http://mmb.pcb.ub.es/~cpons/Cell-Dock. djimenez@ac.upc.edu or juanf@bsc.es Supplementary data are available at Bioinformatics online.

  14. Radiant Cooling for Closed-Loop Water Containment: Exploration of Possible Application in Dry Docks

    Science.gov (United States)

    2015-08-20

    Radiant Cooling For Closed-Loop Water Containment: Exploration of Possible Application in Dry Docks by Trevor R. Murphy, Mechanical...Organization: SPAWAR Sponsoring Organization: NESDI Keywords: Dry Dock Cooling, Heat Transfer, Closed Loop, Pipe System, Cost, Pareto List of Programs...provide data for estimating the cost of implementing a closed-loop radiant cooling system for ships in dry docks . Depending on the material used, pipe

  15. SnapDock-template-based docking by Geometric Hashing.

    Science.gov (United States)

    Estrin, Michael; Wolfson, Haim J

    2017-07-15

    A highly efficient template-based protein-protein docking algorithm, nicknamed SnapDock, is presented. It employs a Geometric Hashing-based structural alignment scheme to align the target proteins to the interfaces of non-redundant protein-protein interface libraries. Docking of a pair of proteins utilizing the 22 600 interface PIFACE library is performed in gmail.com or wolfson@tau.ac.il.

  16. TRANSFER

    African Journals Online (AJOL)

    Abstract. Quenching of curcumine fluorescence by thionine, both immobilised in cellulose acetate occurs in accordance with the Forster mechanism of energy transfer. The rate constant of energy transfer for this donor - acceptor pair is found to be 9.4 x 109 L ' mol S1 with R0 = 37±1 Б. When this donor - acceptor pair is ...

  17. 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.

  18. 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.

  19. 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.

  20. Controlling docks by stubble cultivation

    OpenAIRE

    Dierauer, Hansueli; Siegrist, Franziska; Weidmann, Gilles

    2017-01-01

    The stubble cultivation cuts the dock roots below growth points. The vegetative plant parts are then cut off from the water and nutrient supply, and regrowth is inhibited. Practical recommendation • Summer dock treatment is especially worthwhile in dry summers with catch crop cultivation and after early maturing crops (winter barley, whole-crop silage) or with an early tillage of grass-clover. • After grass-clover lay or cereal harvest, undercut the dock plants at a depth of 12-15 cm...

  1. Evaluation of docking calculations on X-ray structures using CONSENSUS-DOCK.

    Science.gov (United States)

    Okamoto, Masako; Masuda, Yoshiaki; Muroya, Ayumu; Yasuno, Kazuhiro; Takahashi, Osamu; Furuya, Toshio

    2010-12-01

    We are participating in the challenge of identifying active compounds for target proteins using structure-based virtual screening (SBVS). We use an in-house customized docking program, CONSENSUS-DOCK, which is a customized version of the DOCK4 program in which three scoring functions (DOCK4, FlexX and PMF) and consensus scoring have been implemented. This paper compares the docking calculation results obtained using CONSENSUS-DOCK and DOCK4, and demonstrates that CONSENSUS-DOCK produces better results than DOCK4 for major X-ray structures obtained from the Protein Data Bank (PDB).

  2. Enabling Exploration Through Docking Standards

    Science.gov (United States)

    Hatfield, Caris A.

    2012-01-01

    Human exploration missions beyond low earth orbit will likely require international cooperation in order to leverage limited resources. International standards can help enable cooperative missions by providing well understood, predefined interfaces allowing compatibility between unique spacecraft and systems. The International Space Station (ISS) partnership has developed a publicly available International Docking System Standard (IDSS) that provides a solution to one of these key interfaces by defining a common docking interface. The docking interface provides a way for even dissimilar spacecraft to dock for exchange of crew and cargo, as well as enabling the assembly of large space systems. This paper provides an overview of the key attributes of the IDSS, an overview of the NASA Docking System (NDS), and the plans for updating the ISS with IDSS compatible interfaces. The NDS provides a state of the art, low impact docking system that will initially be made available to commercial crew and cargo providers. The ISS will be used to demonstrate the operational utility of the IDSS interface as a foundational technology for cooperative exploration.

  3. DOCK 6: Impact of new features and current docking performance.

    Science.gov (United States)

    Allen, William J; Balius, Trent E; Mukherjee, Sudipto; Brozell, Scott R; Moustakas, Demetri T; Lang, P Therese; Case, David A; Kuntz, Irwin D; Rizzo, Robert C

    2015-06-05

    This manuscript presents the latest algorithmic and methodological developments to the structure-based design program DOCK 6.7 focused on an updated internal energy function, new anchor selection control, enhanced minimization options, a footprint similarity scoring function, a symmetry-corrected root-mean-square deviation algorithm, a database filter, and docking forensic tools. An important strategy during development involved use of three orthogonal metrics for assessment and validation: pose reproduction over a large database of 1043 protein-ligand complexes (SB2012 test set), cross-docking to 24 drug-target protein families, and database enrichment using large active and decoy datasets (Directory of Useful Decoys [DUD]-E test set) for five important proteins including HIV protease and IGF-1R. Relative to earlier versions, a key outcome of the work is a significant increase in pose reproduction success in going from DOCK 4.0.2 (51.4%) → 5.4 (65.2%) → 6.7 (73.3%) as a result of significant decreases in failure arising from both sampling 24.1% → 13.6% → 9.1% and scoring 24.4% → 21.1% → 17.5%. Companion cross-docking and enrichment studies with the new version highlight other strengths and remaining areas for improvement, especially for systems containing metal ions. The source code for DOCK 6.7 is available for download and free for academic users at http://dock.compbio.ucsf.edu/. © 2015 Wiley Periodicals, Inc.

  4. 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.

  5. Text Mining for Protein Docking.

    Science.gov (United States)

    Badal, Varsha D; Kundrotas, Petras J; Vakser, Ilya A

    2015-12-01

    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 benchmark set

  6. 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

  7. 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.

  8. Hydra Rendezvous and Docking Sensor

    Science.gov (United States)

    Roe, Fred; Carrington, Connie

    2007-01-01

    The U.S. technology to support a CEV AR&D activity is mature and was developed by NASA and supporting industry during an extensive research and development program conducted during the 1990's and early 2000 time frame at the Marshall Space Flight Center. Development and demonstration of a rendezvous/docking sensor was identified early in the AR&D Program as the critical enabling technology that allows automated proxinity operations and docking. A first generation rendezvous/docking sensor, the Video Guidance Sensor (VGS) was developed and successfully flown on STS 87 and again on STS 95, proving the concept of a video-based sensor. Advances in both video and signal processing technologies and the lessons learned from the two successful flight experiments provided a baseline for the development of a new generation of video based rendezvous/docking sensor. The Advanced Video Guidance Sensor (AVGS) has greatly increased performance and additional capability for longer-range operation. A Demonstration Automatic Rendezvous Technology (DART) flight experiment was flown in April 2005 using AVGS as the primary proximity operations sensor. Because of the absence of a docking mechanism on the target satellite, this mission did not demonstrate the ability of the sensor to coltrold ocking. Mission results indicate that the rendezvous sensor operated successfully in "spot mode" (2 km acquisition of the target, bearing data only) but was never commanded to "acquire and track" the docking target. Parts obsolescence issues prevent the construction of current design AVGS units to support the NASA Exploration initiative. This flight proven AR&D technology is being modularized and upgraded with additional capabilities through the Hydra project at the Marshall Space Flight Center. Hydra brings a unique engineering approach and sensor architecture to the table, to solve the continuing issues of parts obsolescence and multiple sensor integration. This paper presents an approach to

  9. A Hadoop-based Molecular Docking System

    Science.gov (United States)

    Dong, Yueli; Guo, Quan; Sun, Bin

    2017-10-01

    Molecular docking always faces the challenge of managing tens of TB datasets. It is necessary to improve the efficiency of the storage and docking. We proposed the molecular docking platform based on Hadoop for virtual screening, it provides the preprocessing of ligand datasets and the analysis function of the docking results. A molecular cloud database that supports mass data management is constructed. Through this platform, the docking time is reduced, the data storage is efficient, and the management of the ligand datasets is convenient.

  10. Adaptive BP-Dock: An Induced Fit Docking Approach for Full Receptor Flexibility.

    Science.gov (United States)

    Bolia, Ashini; Ozkan, S Banu

    2016-04-25

    We present an induced fit docking approach called Adaptive BP-Dock that integrates perturbation response scanning (PRS) with the flexible docking protocol of RosettaLigand in an adaptive manner. We first perturb the binding pocket residues of a receptor and obtain a new conformation based on the residue response fluctuation profile using PRS. Next, we dock a ligand to this new conformation by RosettaLigand, where we repeat these steps for several iterations. We test this approach on several protein test sets including difficult unbound docking cases such as HIV-1 reverse transcriptase and HIV-1 protease. Adaptive BP-Dock results show better correlation with experimental binding affinities compared to other docking protocols. Overall, the results imply that Adaptive BP-Dock can easily capture binding induced conformational changes by simultaneous sampling of protein and ligand conformations. This can provide faster and efficient docking of novel targets for rational drug design.

  11. Machine learning in computational docking.

    Science.gov (United States)

    Khamis, Mohamed A; Gomaa, Walid; Ahmed, Walaa F

    2015-03-01

    The objective of this paper is to highlight the state-of-the-art machine learning (ML) techniques in computational docking. The use of smart computational methods in the life cycle of drug design is relatively a recent development that has gained much popularity and interest over the last few years. Central to this methodology is the notion of computational docking which is the process of predicting the best pose (orientation + conformation) of a small molecule (drug candidate) when bound to a target larger receptor molecule (protein) in order to form a stable complex molecule. In computational docking, a large number of binding poses are evaluated and ranked using a scoring function. The scoring function is a mathematical predictive model that produces a score that represents the binding free energy, and hence the stability, of the resulting complex molecule. Generally, such a function should produce a set of plausible ligands ranked according to their binding stability along with their binding poses. In more practical terms, an effective scoring function should produce promising drug candidates which can then be synthesized and physically screened using high throughput screening process. Therefore, the key to computer-aided drug design is the design of an efficient highly accurate scoring function (using ML techniques). The methods presented in this paper are specifically based on ML techniques. Despite many traditional techniques have been proposed, the performance was generally poor. Only in the last few years started the application of the ML technology in the design of scoring functions; and the results have been very promising. The ML-based techniques are based on various molecular features extracted from the abundance of protein-ligand information in the public molecular databases, e.g., protein data bank bind (PDBbind). In this paper, we present this paradigm shift elaborating on the main constituent elements of the ML approach to molecular docking along

  12. Structural Basis for Binding Specificity between Subclasses of Modular Polyketide Synthase Docking Domains

    Energy Technology Data Exchange (ETDEWEB)

    Buchholz, Tonia J.; Geders, Todd W.; Bartley, III, Frank E.; Reynolds, Kevin A.; Smith, Janet L.; Sherman, David H.; (Michigan); (Portland SU)

    2009-04-02

    Bacterial type I polyketide synthases (PKSs) assemble structurally diverse natural products of significant clinical value from simple metabolic building blocks. The synthesis of these compounds occurs in a processive fashion along a large multiprotein complex. Transfer of the acyl intermediate across interpolypeptide junctions is mediated, at least in large part, by N- and C-terminal docking domains. We report here a comprehensive analysis of the binding affinity and selectivity for the complete set of discrete docking domain pairs in the pikromycin and erythromycin PKS systems. Despite disconnection from their parent module, each cognate pair of docking domains retained exquisite binding selectivity. Further insights were obtained by X-ray crystallographic analysis of the PikAIII/PikAIV docking domain interface. This new information revealed a series of key interacting residues that enabled development of a structural model for the recently proposed H2-T2 class of polypeptides involved in PKS intermodular molecular recognition.

  13. 36 CFR 13.1122 - Bartlett Cove Public Use Dock.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Bartlett Cove Public Use Dock... Bartlett Cove § 13.1122 Bartlett Cove Public Use Dock. (a) Docking, tying down, or securing aircraft is prohibited except at the designated aircraft float at the Bartlett Cove Public Use Dock. Docking, tying down...

  14. Demonstration of automated proximity and docking technology

    Science.gov (United States)

    Anderson, Robert L.; Tsugawa, Roy K.; Bryan, Thomas C.

    1991-01-01

    Automated spacecraft docking operations are being performed using a full scale motion based simulator and an optical sensor. This presentation will discuss the work in progress at TRW and MSFC facilities to study the problem of automated proximity and docking operations. The docking sensor used in the MSFC Optical Sensor and simulation runs are performed using the MSFC Flat Floor Facility. The control algorithms and six degrees of freedom (6DOF) simulation software were developed at TRW and integrated into the MSFC facility. Key issues being studied are the quantification of docking sensor requirements and operational constraints necessary to perform automated docking maneuvers, control algorithms capable of performing automated docking in the presence of sensitive and noisy sensor data, and sensor technologies for automated proximity and docking operations. As part of this study the MSFC sensor characteristics were analyzed and modeled so that off line simulation runs can be performed for control algorithm testing. Our goal is to develop and demonstrate full 6DOF docking capabilities with actual sensors on the MSFC motion based simulator. We present findings from actual docking simulation runs which show sensor and control loop performance as well as problem areas which require close attention. The evolution of various control algorithms using both phase plane and Clohessy-Wiltshire techniques are discussed. In addition, 6DOF target acquisition and control strategies are described.

  15. DockFlow - a prototypic PharmaGrid for virtual screening integrating four different docking tools.

    Science.gov (United States)

    Wolf, Antje; Hofmann-Apitius, Martin; Ghanem, Moustafa; Azam, Nabeel; Kalaitzopoulos, Dimitrios; Yu, Kunqian; Kasam, Vinod

    2009-01-01

    In this paper we present DockFlow, a prototypic version of a PharmaGrid. DockFlow is supporting pharmaceutical research through enabling virtual screening on the Grid. The system was developed in the course of the BRIDGE project funded by the European Commission. Grids have been used before to run compute- and data-intensive virtual screening experiments, like in the WISDOM project. With DockFlow, however, we addressed a variety of problems yet unsolved, like the diversity of results produced by different docking tools. We also addressed the problem of analysing the data produced in a distributed virtual screening system applying a combinatorial docking approach. In DockFlow we worked on a grid-based problem solving environment for virtual screening with the following major features: execution of four different docking services (FlexX, AutoDock, DOCK and GAsDock) at locations in Europe and China remotely from a common workflow, storage of the results in a common Docking Database providing a shared analysis platform for the collaboration partners and combination of the results. The DockFlow prototype is evaluated on two scientific case studies: malaria and avian flu.

  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 5...

  17. Autoguidance video sensor for docking

    Science.gov (United States)

    Book, Michael L.; Bryan, Thomas C.; Howard, Richard T.; Dabney, Richard W.

    1992-01-01

    The Automated Rendezvous and Docking system (ARAD) is composed of two parts. The first part is the sensor which consists of a video camera ringed with two wavelengths of laser diode. The second part is a standard Remote Manipulator System (RMS) target used on the Orbiter that has been modified with three circular pieces of retro-reflective tape covered by optical filters which correspond to one of the wavelengths of laser diode. The sensor is on the chase vehicle and the target is on the target vehicle. The ARAD system works by pulsing one wavelength laser diodes and taking a picture. Then the second wavelength laser diodes are pulsed and a second picture is taken. One picture is subtracted from the other and the resultant picture is thresholded. All adjacent pixels above threshold are blobbed together (X and Y centroids calculated). All blob centroids are checked to recognize the target out of noise. Then the three target spots are windowed and tracked. The three target spot centroids are used to evaluate the roll, yaw, pitch, range, azimuth, and elevation. From that a guidance routine can guide the chase vehicle to dock with the target vehicle with the correct orientation.

  18. 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...

  19. SwarmDock: a server for flexible protein-protein docking.

    Science.gov (United States)

    Torchala, Mieczyslaw; Moal, Iain H; Chaleil, Raphael A G; Fernandez-Recio, Juan; Bates, Paul A

    2013-03-15

    Protein-protein interactions are central to almost all biological functions, and the atomic details of such interactions can yield insights into the mechanisms that underlie these functions. We present a web server that wraps and extends the SwarmDock flexible protein-protein docking algorithm. After uploading PDB files of the binding partners, the server generates low energy conformations and returns a ranked list of clustered docking poses and their corresponding structures. The user can perform full global docking, or focus on particular residues that are implicated in binding. The server is validated in the CAPRI blind docking experiment, against the most current docking benchmark, and against the ClusPro docking server, the highest performing server currently available.

  20. PTools: an opensource molecular docking library.

    Science.gov (United States)

    Saladin, Adrien; Fiorucci, Sébastien; Poulain, Pierre; Prévost, Chantal; Zacharias, Martin

    2009-05-01

    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. 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. 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.

  1. 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...... search spaces effectively and is one of the commonly used methods for flexible ligand docking. During the last decade, several EAs using different variation operators have been introduced, such as the ones provided with the AutoDock program. In this paper we evaluate the performance of different EA...... settings such as choice of variation operators, population size, and usage of local search. The comparison is performed on a suite of six docking problems previously used to evaluate the performance of search algorithms provided with the AutoDock program package. The results from our investigation confirm...

  2. Why are most EU pigs tail docked?

    DEFF Research Database (Denmark)

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

    2016-01-01

    for Danish production (0.7 m2/pig); ‘Standard Undocked’, which is the same as ‘Standard Docked’ but with no tail docking, ‘Efficient Undocked’ and ‘Enhanced Undocked’, which have increased solid floor area (0.9 and 1.0 m2/pig, respectively) provision of loose manipulable materials (100 and 200 g/straw per...... pig per day) and no tail docking. A decision tree model based on data from Danish and Finnish pig production suggests that Standard Docked provides the highest economic gross margin with the least tail biting. Given our assumptions, Enhanced Undocked is the least economic, although Efficient Undocked...... and enforcement by Member States. Widespread use of tail docking seems to be accepted, mainly because the alternative steps that producers are required to take before resorting to it are not specified in detail. By tail docking, producers are acting in their own best interests. We suggest that for the practice...

  3. Methodology for Developing a Probabilistic Risk Assessment Model of Spacecraft Rendezvous and Dockings

    Science.gov (United States)

    Farnham, Steven J., II; Garza, Joel, Jr.; Castillo, Theresa M.; Lutomski, Michael

    2011-01-01

    In 2007 NASA was preparing to send two new visiting vehicles carrying logistics and propellant to the International Space Station (ISS). These new vehicles were the European Space Agency s (ESA) Automated Transfer Vehicle (ATV), the Jules Verne, and the Japanese Aerospace and Explorations Agency s (JAXA) H-II Transfer Vehicle (HTV). The ISS Program wanted to quantify the increased risk to the ISS from these visiting vehicles. At the time, only the Shuttle, the Soyuz, and the Progress vehicles rendezvoused and docked to the ISS. The increased risk to the ISS was from an increase in vehicle traffic, thereby, increasing the potential catastrophic collision during the rendezvous and the docking or berthing of the spacecraft to the ISS. A universal method of evaluating the risk of rendezvous and docking or berthing was created by the ISS s Risk Team to accommodate the increasing number of rendezvous and docking or berthing operations due to the increasing number of different spacecraft, as well as the future arrival of commercial spacecraft. Before the first docking attempt of ESA's ATV and JAXA's HTV to the ISS, a probabilistic risk model was developed to quantitatively calculate the risk of collision of each spacecraft with the ISS. The 5 rendezvous and docking risk models (Soyuz, Progress, Shuttle, ATV, and HTV) have been used to build and refine the modeling methodology for rendezvous and docking of spacecrafts. This risk modeling methodology will be NASA s basis for evaluating the addition of future ISS visiting spacecrafts hazards, including SpaceX s Dragon, Orbital Science s Cygnus, and NASA s own Orion spacecraft. This paper will describe the methodology used for developing a visiting vehicle risk model.

  4. 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.

  5. Rosetta Ligand docking with flexible XML protocols.

    Science.gov (United States)

    Lemmon, Gordon; Meiler, Jens

    2012-01-01

    RosettaLigand is premiere software for predicting how a protein and a small molecule interact. Benchmark studies demonstrate that 70% of the top scoring RosettaLigand predicted interfaces are within 2Å RMSD from the crystal structure [1]. The latest release of Rosetta ligand software includes many new features, such as (1) docking of multiple ligands simultaneously, (2) representing ligands as fragments for greater flexibility, (3) redesign of the interface during docking, and (4) an XML script based interface that gives the user full control of the ligand docking protocol.

  6. 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...... surrogate and homology modeling template for the nAChRs, the conformation of this loop is controlled by the ligand present in the binding pocket. As part of the development of a protocol for unbiased docking to the nAChRs, we here present the results of docking of ligands with known binding modes to an ACh...

  7. 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 bet...

  8. 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,

  9. GPU.proton.DOCK: Genuine Protein Ultrafast proton equilibria consistent DOCKing.

    Science.gov (United States)

    Kantardjiev, Alexander A

    2011-07-01

    GPU.proton.DOCK (Genuine Protein Ultrafast proton equilibria consistent DOCKing) is a state of the art service for in silico prediction of protein-protein interactions via rigorous and ultrafast docking code. It is unique in providing stringent account of electrostatic interactions self-consistency and proton equilibria mutual effects of docking partners. GPU.proton.DOCK is the first server offering such a crucial supplement to protein docking algorithms--a step toward more reliable and high accuracy docking results. The code (especially the Fast Fourier Transform bottleneck and electrostatic fields computation) is parallelized to run on a GPU supercomputer. The high performance will be of use for large-scale structural bioinformatics and systems biology projects, thus bridging physics of the interactions with analysis of molecular networks. We propose workflows for exploring in silico charge mutagenesis effects. Special emphasis is given to the interface-intuitive and user-friendly. The input is comprised of the atomic coordinate files in PDB format. The advanced user is provided with a special input section for addition of non-polypeptide charges, extra ionogenic groups with intrinsic pK(a) values or fixed ions. The output is comprised of docked complexes in PDB format as well as interactive visualization in a molecular viewer. GPU.proton.DOCK server can be accessed at http://gpudock.orgchm.bas.bg/.

  10. PSI-DOCK: towards highly efficient and accurate flexible ligand docking.

    Science.gov (United States)

    Pei, Jianfeng; Wang, Qi; Liu, Zhenming; Li, Qingliang; Yang, Kun; Lai, Luhua

    2006-03-01

    We have developed a new docking method, Pose-Sensitive Inclined (PSI)-DOCK, for flexible ligand docking. An improved SCORE function has been developed and used in PSI-DOCK for binding free energy evaluation. The improved SCORE function was able to reproduce the absolute binding free energies of a training set of 200 protein-ligand complexes with a correlation coefficient of 0.788 and a standard error of 8.13 kJ/mol. For ligand binding pose exploration, a unique searching strategy was designed in PSI-DOCK. In the first step, a tabu-enhanced genetic algorithm with a rapid shape-complementary scoring function is used to roughly explore and store potential binding poses of the ligand. Then, these predicted binding poses are optimized and compete against each other by using a genetic algorithm with the accurate SCORE function to determine the binding pose with the lowest docking energy. The PSI-DOCK 1.0 program is highly efficient in identifying the experimental binding pose. For a test dataset of 194 complexes, PSI-DOCK 1.0 achieved a 67% success rate (RMSD DOCK can also predict the docking binding free energy with high accuracy. For a test set of 64 complexes, the correlation between the experimentally observed binding free energies and the docking binding free energies for 64 complexes is r = 0.777 with a standard deviation of 7.96 kJ/mol. Moreover, compared with other docking methods, PSI-DOCK 1.0 is extremely easy to use and requires minimum docking preparations. There is no requirement for the users to add hydrogen atoms to proteins because all protein hydrogen atoms and the flexibility of the terminal protein atoms are intrinsically taken into account in PSI-DOCK. There is also no requirement for the users to calculate partial atomic charges because PSI-DOCK does not calculate an electrostatic energy term. These features are not only convenient for the users but also help to avoid the influence of different preparation methods. 2006 Wiley-Liss, Inc.

  11. The issues of endurance when docking vessels in floating docks (review)

    OpenAIRE

    ANTONENKO SERGEY

    2017-01-01

    Large capacity docks are relatively infrequently loaded with commensurate vessels. In this context, one of the ways to enhance the operational efficiency of docks is handling ships in groups. The mechanical stress-strain state of the structure including a steel pontoon dock with vessels in it is hard to calculate and it may entail failures in its endurance. Of particular interest is the case of a large-capacity vessel and several small-displacement ones making up a dock group. Large displ...

  12. Next generation of dock safety equipment.

    Science.gov (United States)

    Swietlik, Walt

    2013-09-01

    OSHA and forklift manufacturers have made extensive efforts to improve the safety of forklift operation in and around industrial facilities and warehouses. However, the use of next-generation vehicle restraint and light communications technology will go much farther toward protecting forklift operators and pedestrians, reducing accidents, and improving productivity at the loading dock. While these new technologies mark a significant advance in loading dock safety, they cannot replace forklift and loading dock safety policies. Employers must continue to focus on forklift safety training and consider the use of multiple safety devices, such as strategically placed signs, painted aisles, and guarded walkways. The best practice is to seek the advice of safety consultants and qualified loading dock equipment representatives.

  13. 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.

  14. Long Range Validation of ATV-ISS Rendez-Vous and Docking Using EPOSx

    Science.gov (United States)

    Schreutelkamp, E.

    2008-08-01

    On April 3 at 16:40, Jules Verne, the first of a series at least 5 Automated Transfer Vehicles (ATV) docked successfully and safely at the International Space Station (ISS). This paper describes the very large test facility that was needed to perform the validation of the Rendez Vous and Docking (RVD) of this safety critical process. It describes the facility in detail as well as the Hardware and Software mechanisms needed to perform these tests at such a large scale while still meeting the high accuracy and safety requirements for the docking procedures. Furthermore it describes the environmental conditions needed to be such that the real flight hardware could be used without risk. The paper also tries to answer the question if designing such a large test facility so late into the ATV development process was a wise decision and if all that effort paid off in the end.

  15. Status of GPCR modeling and docking as reflected by community-wide GPCR Dock 2010 assessment.

    NARCIS (Netherlands)

    Kufareva, I.; Rueda, M.; Katritch, V.; Stevens, R.C.; Abagyan, R.; Vroling, B.; Sanders, M.P.A.

    2011-01-01

    The community-wide GPCR Dock assessment is conducted to evaluate the status of molecular modeling and ligand docking for human G protein-coupled receptors. The present round of the assessment was based on the recent structures of dopamine D3 and CXCR4 chemokine receptors bound to small molecule

  16. Status of GPCR Modeling and Docking as Reflected by Community-wide GPCR Dock 2010 Assessment

    NARCIS (Netherlands)

    Kufareva, I; Rueda, M; Katritch, V; Roumen, L.; de Esch, I.J.P.; Leurs, R.; de Graaf, C.; Stevens, R.C.; Abagyan, R

    2011-01-01

    The community-wide GPCR Dock assessment is conducted to evaluate the status of molecular modeling and ligand docking for human G protein-coupled receptors. The present round of the assessment was based on the recent structures of dopamine D3 and CXCR4 chemokine receptors bound to small molecule

  17. DockQ: A Quality Measure for Protein-Protein Docking Models.

    Directory of Open Access Journals (Sweden)

    Sankar Basu

    Full Text Available The state-of-the-art to assess the structural quality of docking models is currently based on three related yet independent quality measures: Fnat, LRMS, and iRMS as proposed and standardized by CAPRI. These quality measures quantify different aspects of the quality of a particular docking model and need to be viewed together to reveal the true quality, e.g. a model with relatively poor LRMS (>10Å might still qualify as 'acceptable' with a descent Fnat (>0.50 and iRMS (<3.0Å. This is also the reason why the so called CAPRI criteria for assessing the quality of docking models is defined by applying various ad-hoc cutoffs on these measures to classify a docking model into the four classes: Incorrect, Acceptable, Medium, or High quality. This classification has been useful in CAPRI, but since models are grouped in only four bins it is also rather limiting, making it difficult to rank models, correlate with scoring functions or use it as target function in machine learning algorithms. Here, we present DockQ, a continuous protein-protein docking model quality measure derived by combining Fnat, LRMS, and iRMS to a single score in the range [0, 1] that can be used to assess the quality of protein docking models. By using DockQ on CAPRI models it is possible to almost completely reproduce the original CAPRI classification into Incorrect, Acceptable, Medium and High quality. An average PPV of 94% at 90% Recall demonstrating that there is no need to apply predefined ad-hoc cutoffs to classify docking models. Since DockQ recapitulates the CAPRI classification almost perfectly, it can be viewed as a higher resolution version of the CAPRI classification, making it possible to estimate model quality in a more quantitative way using Z-scores or sum of top ranked models, which has been so valuable for the CASP community. The possibility to directly correlate a quality measure to a scoring function has been crucial for the development of scoring functions for

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

    Directory of Open Access Journals (Sweden)

    Rezaul Chowdhury

    Full Text Available 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.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.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: http

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

    Science.gov (United States)

    Chowdhury, Rezaul; Rasheed, Muhibur; Keidel, Donald; Moussalem, Maysam; Olson, Arthur; Sanner, Michel; Bajaj, Chandrajit

    2013-01-01

    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. 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. 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: http

  20. Protein-Protein Docking with F2Dock 2.0 and GB-Rerank

    Science.gov (United States)

    Chowdhury, Rezaul; Rasheed, Muhibur; Keidel, Donald; Moussalem, Maysam; Olson, Arthur; Sanner, Michel; Bajaj, Chandrajit

    2013-01-01

    Motivation Computational simulation of protein-protein docking can expedite the process of molecular modeling and drug discovery. This paper reports on our new F2 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 F2 Dock 2.0 with ZDock 3.0.2 and found improvements over it, specifically among 176 complexes in ZLab Benchmark 4.0, F2 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. F2 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 F2 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: http

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. SAMPL4 & DOCK3.7: lessons for automated docking procedures

    Science.gov (United States)

    Coleman, Ryan G.; Sterling, Teague; Weiss, Dahlia R.

    2014-03-01

    The SAMPL4 challenges were used to test current automated methods for solvation energy, virtual screening, pose and affinity prediction of the molecular docking pipeline DOCK 3.7. Additionally, first-order models of binding affinity were proposed as milestones for any method predicting binding affinity. Several important discoveries about the molecular docking software were made during the challenge: (1) Solvation energies of ligands were five-fold worse than any other method used in SAMPL4, including methods that were similarly fast, (2) HIV Integrase is a challenging target, but automated docking on the correct allosteric site performed well in terms of virtual screening and pose prediction (compared to other methods) but affinity prediction, as expected, was very poor, (3) Molecular docking grid sizes can be very important, serious errors were discovered with default settings that have been adjusted for all future work. Overall, lessons from SAMPL4 suggest many changes to molecular docking tools, not just DOCK 3.7, that could improve the state of the art. Future difficulties and projects will be discussed.

  6. Quantum.Ligand.Dock: protein-ligand docking with quantum entanglement refinement on a GPU system.

    Science.gov (United States)

    Kantardjiev, Alexander A

    2012-07-01

    Quantum.Ligand.Dock (protein-ligand docking with graphic processing unit (GPU) quantum entanglement refinement on a GPU system) is an original modern method for in silico prediction of protein-ligand interactions via high-performance docking code. The main flavour of our approach is a combination of fast search with a special account for overlooked physical interactions. On the one hand, we take care of self-consistency and proton equilibria mutual effects of docking partners. On the other hand, Quantum.Ligand.Dock is the the only docking server offering such a subtle supplement to protein docking algorithms as quantum entanglement contributions. The motivation for development and proposition of the method to the community hinges upon two arguments-the fundamental importance of quantum entanglement contribution in molecular interaction and the realistic possibility to implement it by the availability of supercomputing power. The implementation of sophisticated quantum methods is made possible by parallelization at several bottlenecks on a GPU supercomputer. The high-performance implementation will be of use for large-scale virtual screening projects, structural bioinformatics, systems biology and fundamental research in understanding protein-ligand recognition. The design of the interface is focused on feasibility and ease of use. Protein and ligand molecule structures are supposed to be submitted as atomic coordinate files in PDB format. A customization section is offered for addition of user-specified charges, extra ionogenic groups with intrinsic pK(a) values or fixed ions. Final predicted complexes are ranked according to obtained scores and provided in PDB format as well as interactive visualization in a molecular viewer. Quantum.Ligand.Dock server can be accessed at http://87.116.85.141/LigandDock.html.

  7. Vehicle routing with cross-docking

    DEFF Research Database (Denmark)

    Wen, Min; Larsen, Jesper; Clausen, Jens

    2009-01-01

    Over the past decade, cross-docking has emerged as an important material handling technology in transportation. A variation of the well-known Vehicle Routing Problem (VRP), the VRP with Cross-Docking (VRPCD) arises in a number of logistics planning contexts. This paper addresses the VRPCD, where...... procedure to solve the problem. The proposed algorithm is implemented and tested on data sets provided by the Danish consultancy Transvision, and involving up to 200 pairs of nodes. Experimental results show that this algorithm can produce high-quality solutions (less than 5% away from optimal solution...

  8. 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.

  9. A Novel Docking System for Modular Self-Reconfigurable Robots

    Directory of Open Access Journals (Sweden)

    Tan Zhang

    2017-10-01

    Full Text Available Existing self-reconfigurable robots achieve connections and disconnections by a separate drive of the docking system. In this paper, we present a new docking system with which the connections and disconnections are driven by locomotion actuators, without the need for a separate drive, which reduces the weight and the complexity of the modules. This self-reconfigurable robot consists of two types of fundamental modules, i.e., active and passive modules. By the docking system, two types of connections are formed with the fundamental modules, and the docking and undocking actions are achieved through simple control with less sensory feedback. This paper describes the design of the robotic modules, the docking system, the docking process, and the docking force analysis. An experiment is performed to demonstrate the self-reconfigurable robot with the docking system.

  10. Dock-family exchange factors in cell migration and disease.

    Science.gov (United States)

    Gadea, Gilles; Blangy, Anne

    2014-10-01

    Dock family proteins are evolutionary conserved exchange factors for the Rho GTPases Rac and Cdc42. There are 11 Dock proteins in mammals, named Dock1 (or Dock180) to Dock11 that play different cellular functions. In particular, Dock proteins regulate actin cytoskeleton, cell adhesion and migration. Not surprisingly, members of the Dock family have been involved in various pathologies, including cancer and defects in the central nervous and immune systems. This review proposes an update of the recent findings regarding the function of Dock proteins, focusing on their role in the control of cell migration and invasion and the consequences in human diseases. Copyright © 2014 Elsevier GmbH. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    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...... problems of four warehouses of a large retailer and show that substantially smaller cross-docks can be used by using dock-doors flexibly and properly scheduling the trucks....

  12. Pharmacophore-based similarity scoring for DOCK.

    Science.gov (United States)

    Jiang, Lingling; Rizzo, Robert C

    2015-01-22

    Pharmacophore modeling incorporates geometric and chemical features of known inhibitors and/or targeted binding sites to rationally identify and design new drug leads. In this study, we have encoded a three-dimensional pharmacophore matching similarity (FMS) scoring function into the structure-based design program DOCK. Validation and characterization of the method are presented through pose reproduction, crossdocking, and enrichment studies. When used alone, FMS scoring dramatically improves pose reproduction success to 93.5% (∼20% increase) and reduces sampling failures to 3.7% (∼6% drop) compared to the standard energy score (SGE) across 1043 protein-ligand complexes. The combined FMS+SGE function further improves success to 98.3%. Crossdocking experiments using FMS and FMS+SGE scoring, for six diverse protein families, similarly showed improvements in success, provided proper pharmacophore references are employed. For enrichment, incorporating pharmacophores during sampling and scoring, in most cases, also yield improved outcomes when docking and rank-ordering libraries of known actives and decoys to 15 systems. Retrospective analyses of virtual screenings to three clinical drug targets (EGFR, IGF-1R, and HIVgp41) using X-ray structures of known inhibitors as pharmacophore references are also reported, including a customized FMS scoring protocol to bias on selected regions in the reference. Overall, the results and fundamental insights gained from this study should benefit the docking community in general, particularly researchers using the new FMS method to guide computational drug discovery with DOCK.

  13. idDock+: Integrating Machine Learning in Probabilistic Search for Protein-Protein Docking.

    Science.gov (United States)

    Hashmi, Irina; Shehu, Amarda

    2015-09-01

    Predicting the three-dimensional native structures of protein dimers, a problem known as protein-protein docking, is key to understanding molecular interactions. Docking is a computationally challenging problem due to the diversity of interactions and the high dimensionality of the configuration space. Existing methods draw configurations systematically or at random from the configuration space. The inaccuracy of scoring functions used to evaluate drawn configurations presents additional challenges. Evidence is growing that optimization of a scoring function is an effective technique only once the drawn configuration is sufficiently similar to the native structure. Therefore, in this article we present a method that employs optimization of a sophisticated energy function, FoldX, only to locally improve a promising configuration. The main question of how promising configurations are identified is addressed through a machine learning method trained a priori on an extensive dataset of functionally diverse protein dimers. To deal with the vast configuration space, a probabilistic search algorithm operates on top of the learner, feeding to it configurations drawn at random. We refer to our method as idDock+, for informatics-driven Docking. idDock+is tested on 15 dimers of different sizes and functional classes. Analysis shows that on all systems idDock+finds a near-native structure and is comparable in accuracy to other state-of-the-art methods. idDock+ represents one of the first highly efficient hybrid methods that combines fast machine learning models with demanding optimization of sophisticated energy scoring functions. Our results indicate that this is a promising direction to improve both efficiency and accuracy in docking.

  14. GradDock: Rapid Simulation and Tailored Ranking Functions for Peptide-MHC Class I Docking.

    Science.gov (United States)

    Kyeong, Hyun-Ho; Choi, Yoonjoo; Kim, Hak-Sung

    2017-09-18

    The identification of T-cell epitopes has many profound translational applications in the areas of transplantation, disease diagnosis, vaccine/therapeutic protein development and personalized immunotherapy. While data-driven methods have been widely used for the prediction of peptide binders with notable successes, the structural modeling of peptide binding to MHC molecules is crucial for understanding the underlying molecular mechanism of the immunological processes. We developed GradDock, a structure-based method for the rapid and accurate modeling of peptide binding to MHC class I (pMHC-I). GradDock explicitly models diverse unbound peptides in vacuo and inserts them into the MHC-I groove through a steered gradient descent with a topological correction process. The simulation process yields diverse structural conformations including native-like peptides. We completely revised the Rosetta score terms and developed a new ranking function specifically for pMHC-I. Using the diverse peptides, a linear programming approach is applied to find the optimal weights for the individual Rosetta score terms. Our examination revealed that a refinement of the dihedral angles and a modification of the repulsion can dramatically improve the modeling quality. GradDock is five-times faster than a Rosetta-based docking approach for pMHC-I. We also demonstrate that the predictive capability of GradDock with the re-weighted Rosetta ranking function is consistently more accurate than the Rosetta-based method with the standard Rosetta score (approximately three-times better for a cross-docking set). GradDock is freely available for academic purposes. The program and the ranking score weights for Rosetta are available at http://bel.kaist.ac.kr/research/GradDock . Supplementary data are available at Bioinformatics online.

  15. 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.

  16. The effect of dock length on harbour siltation

    Science.gov (United States)

    van Maren, Dirk Sebastiaan; Winterwerp, Johan C.; Sas, Marc; Vanlede, Joris

    2009-06-01

    Density-driven exchange flows between estuaries and harbour docks are influenced by the length of the dock. As a result, increasing dock size through its lengthening, not necessarily results in an increase in sedimentation rates. The propagation of a low-salinity surface patch into the dock is blocked at the head of a relatively short dock, resulting in a reversal of density-driven flows, and a reduction of the hydrostatic pressure gradients in the entrance of the dock. A reduced hydrostatic pressure in the dock, in turn, promotes near-bed inflow. When this increased near-bed inflow coincides with a high sediment supply on the adjacent river, the sediment transport into the dock increases. This has been tested with an extensively validated high-resolution numerical model developed for the Deurganckdok in the Port of Antwerp. In the Deurganckdok, siltation rates are expected to decrease when the dock is fully excavated compared to the present half-opened dock. Whether exchange flows between estuaries and harbour docks are influenced by the length of the dock, depends on the tidal variation in salinity. For small tidal density variations (around 0.5 kg/m 3), the dock length is expected to influence exchange flows in a short dock (approximately 1 km), whereas the dock should be much longer (4 km) when the tidal density variation is higher (around 5 kg/m 3). Whether these changing exchange flow result in a lowering or increase of sediment import, depends on the phase difference between sediment concentration peaks on the adjacent river/estuary and the salinity variation, and on the vertical distribution of sediment.

  17. Dock protein family in brain development and neurological disease.

    Science.gov (United States)

    Shi, Lei

    2013-11-01

    The family of dedicator of cytokinesis (Dock), a protein family that belongs to the atypical Rho guanine nucleotide exchange factors (GEFs) for Rac and/or Cdc42 GTPases, plays pivotal roles in various processes of brain development. To date, 11 members of Docks have been identified in the mammalian system. Emerging evidence has suggested that members of the Dock family are associated with several neurodegenerative and neuropsychiatric diseases, including Alzheimer disease and autism spectrum disorders. This review summarizes recent advances on the understanding of the roles of the Dock protein family in normal and diseased processes in the nervous system. Furthermore, interacting proteins and the molecular regulation of Docks are discussed.

  18. CALET docked on the ISS

    CERN Multimedia

    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...

  19. MS-DOCK: accurate multiple conformation generator and rigid docking protocol for multi-step virtual ligand screening.

    Science.gov (United States)

    Sauton, Nicolas; Lagorce, David; Villoutreix, Bruno O; Miteva, Maria A

    2008-04-10

    The number of protein targets with a known or predicted tri-dimensional structure and of drug-like chemical compounds is growing rapidly and so is the need for new therapeutic compounds or chemical probes. Performing flexible structure-based virtual screening computations on thousands of targets with millions of molecules is intractable to most laboratories nor indeed desirable. Since shape complementarity is of primary importance for most protein-ligand interactions, we have developed a tool/protocol based on rigid-body docking to select compounds that fit well into binding sites. Here we present an efficient multiple conformation rigid-body docking approach, MS-DOCK, which is based on the program DOCK. This approach can be used as the first step of a multi-stage docking/scoring protocol. First, we developed and validated the Multiconf-DOCK tool that generates several conformers per input ligand. Then, each generated conformer (bioactives and 37970 decoys) was docked rigidly using DOCK6 with our optimized protocol into seven different receptor-binding sites. MS-DOCK was able to significantly reduce the size of the initial input library for all seven targets, thereby facilitating subsequent more CPU demanding flexible docking procedures. MS-DOCK can be easily used for the generation of multi-conformer libraries and for shape-based filtering within a multi-step structure-based screening protocol in order to shorten computation times.

  20. Flexible ligand docking using a genetic algorithm

    Science.gov (United States)

    Oshiro, C. M.; Kuntz, I. D.; Dixon, J. Scott

    1995-04-01

    Two computational techniques have been developed to explore the orientational and conformational space of a flexible ligand within an enzyme. Both methods use the Genetic Algorithm (GA) to generate conformationally flexible ligands in conjunction with algorithms from the DOCK suite of programs to characterize the receptor site. The methods are applied to three enzyme-ligand complexes: dihydrofolate reductase-methotrexate, thymidylate synthase-phenolpthalein and HIV protease-thioketal haloperidol. Conformations and orientations close to the crystallographically determined structures are obtained, as well as alternative structures with low energy. The potential for the GA method to screen a database of compounds is also examined. A collection of ligands is evaluated simultaneously, rather than docking the ligands individually into the enzyme.

  1. Laser space rendezvous and docking tradeoff

    Science.gov (United States)

    Adelman, S.; Levinson, S.; Raber, P.; Weindling, F.

    1974-01-01

    A spaceborne laser radar (LADAR) was configured to meet the requirements for rendezvous and docking with a cooperative object in synchronous orbit. The LADAR, configurated using existing pulsed CO2 laser technology and a 1980 system technology baseline, is well suited for the envisioned space tug missions. The performance of a family of candidate LADARS was analyzed. Tradeoff studies as a function of size, weight, and power consumption were carried out for maximum ranges of 50, 100, 200, and 300 nautical miles. The investigation supports the original contention that a rendezvous and docking LADAR can be constructed to offer a cost effective and reliable solution to the envisioned space missions. In fact, the CO2 ladar system offers distinct advantages over other candidate systems.

  2. BP-Dock: a flexible docking scheme for exploring protein-ligand interactions based on unbound structures.

    Science.gov (United States)

    Bolia, Ashini; Gerek, Z Nevin; Ozkan, S Banu

    2014-03-24

    Molecular docking serves as an important tool in modeling protein-ligand interactions. However, it is still challenging to incorporate overall receptor flexibility, especially backbone flexibility, in docking due to the large conformational space that needs to be sampled. To overcome this problem, we developed a novel flexible docking approach, BP-Dock (Backbone Perturbation-Dock) that can integrate both backbone and side chain conformational changes induced by ligand binding through a multi-scale approach. In the BP-Dock method, we mimic the nature of binding-induced events as a first-order approximation by perturbing the residues along the protein chain with a small Brownian kick one at a time. The response fluctuation profile of the chain upon these perturbations is computed using the perturbation response scanning method. These response fluctuation profiles are then used to generate binding-induced multiple receptor conformations for ensemble docking. To evaluate the performance of BP-Dock, we applied our approach on a large and diverse data set using unbound structures as receptors. We also compared the BP-Dock results with bound and unbound docking, where overall receptor flexibility was not taken into account. Our results highlight the importance of modeling backbone flexibility in docking for recapitulating the experimental binding affinities, especially when an unbound structure is used. With BP-Dock, we can generate a wide range of binding site conformations realized in nature even in the absence of a ligand that can help us to improve the accuracy of unbound docking. We expect that our fast and efficient flexible docking approach may further aid in our understanding of protein-ligand interactions as well as virtual screening of novel targets for rational drug design.

  3. Docking protein domains in contact space

    Directory of Open Access Journals (Sweden)

    Walker-Taylor Alice

    2006-06-01

    Full Text Available Abstract Background Many biological processes involve the physical interaction between protein domains. Understanding these functional associations requires knowledge of the molecular structure. Experimental investigations though present considerable difficulties and there is therefore a need for accurate and reliable computational methods. In this paper we present a novel method that seeks to dock protein domains using a contact map representation. Rather than providing a full three dimensional model of the complex, the method predicts contacting residues across the interface. We use a scoring function that combines structural, physicochemical and evolutionary information, where each potential residue contact is assigned a value according to the scoring function and the hypothesis is that the real configuration of contacts is the one that maximizes the score. The search is performed with a simulated annealing algorithm directly in contact space. Results We have tested the method on interacting domain pairs that are part of the same protein (intra-molecular domains. We show that it correctly predicts some contacts and that predicted residues tend to be significantly closer to each other than other pairs of residues in the same domains. Moreover we find that predicted contacts can often discriminate the best model (or the native structure, if present among a set of optimal solutions generated by a standard docking procedure. Conclusion Contact docking appears feasible and able to complement other computational methods for the prediction of protein-protein interactions. With respect to more standard docking algorithms it might be more suitable to handle protein conformational changes and to predict complexes starting from protein models.

  4. ParaDockS: a framework for molecular docking with population-based metaheuristics.

    Science.gov (United States)

    Meier, René; Pippel, Martin; Brandt, Frank; Sippl, Wolfgang; Baldauf, Carsten

    2010-05-24

    Molecular docking is a simulation technique that aims to predict the binding pose between a ligand and a receptor. The resulting multidimensional continuous optimization problem is practically unsolvable in an exact way. One possible approach is the combination of an optimization algorithm and an objective function that describes the interaction. The software ParaDockS is designed to hold different optimization algorithms and objective functions. At the current stage, an adapted particle-swarm optimizer (PSO) is implemented. Available objective functions are (i) the empirical objective function p-Score and (ii) an adapted version of the knowledge-based potential PMF04. We tested the docking accuracy in terms of reproducing known crystal structures from the PDBbind core set. For 73% of the test instances the native binding mode was found with an rmsd below 2 A. The virtual screening efficiency was tested with a subset of 13 targets and the respective ligands and decoys from the directory of useful decoys (DUD). ParaDockS with PMF04 shows a superior early enrichment. The here presented approach can be employed for molecular docking experiments and virtual screenings of large compound libraries in academia as well as in industrial research and development. The performance in terms of accuracy and enrichment is close to the results of commercial software solutions.

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

    Science.gov (United States)

    Herskin, M S; Thodberg, K; Jensen, H E

    2015-04-01

    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. The tail lengths and diameters differed at slaughter (lengths: 30.6±0.6; 24.9±0.4; 19.8±0.6; 8.7±0.6 cm; Ptail diameter: 0.5±0.03; 0.8±0.02; 1.0±0.03; 1.4±0.04 cm; Ptails with neuromas (64 v. 0%; Ptail (1.0±0.2 v. 0; Ptail docking piglets using hot-iron cautery causes formation of neuromas in the outermost part of the tail tip. The presence of neuromas might lead to altered nociceptive thresholds, which need to be confirmed in future studies.

  6. 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

    2016-01-01

    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/. PMID:27131368

  7. Modeling of protein-peptide interactions using the CABS-dock web server for binding site search and flexible docking.

    Science.gov (United States)

    Blaszczyk, Maciej; Kurcinski, Mateusz; Kouza, Maksim; Wieteska, Lukasz; Debinski, Aleksander; Kolinski, Andrzej; Kmiecik, Sebastian

    2016-01-15

    Protein-peptide interactions play essential functional roles in living organisms and their structural characterization is a hot subject of current experimental and theoretical research. Computational modeling of the structure of protein-peptide interactions is usually divided into two stages: prediction of the binding site at a protein receptor surface, and then docking (and modeling) the peptide structure into the known binding site. This paper presents a comprehensive CABS-dock method for the simultaneous search of binding sites and flexible protein-peptide docking, available as a user's friendly web server. We present example CABS-dock results obtained in the default CABS-dock mode and using its advanced options that enable the user to increase the range of flexibility for chosen receptor fragments or to exclude user-selected binding modes from docking search. Furthermore, we demonstrate a strategy to improve CABS-dock performance by assessing the quality of models with classical molecular dynamics. Finally, we discuss the promising extensions and applications of the CABS-dock method and provide a tutorial appendix for the convenient analysis and visualization of CABS-dock results. The CABS-dock web server is freely available at http://biocomp.chem.uw.edu.pl/CABSdock/. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  8. GeauxDock: A novel approach for mixed-resolution ligand docking using a descriptor-based force field.

    Science.gov (United States)

    Ding, Yun; Fang, Ye; Feinstein, Wei P; Ramanujam, Jagannathan; Koppelman, David M; Moreno, Juana; Brylinski, Michal; Jarrell, Mark

    2015-10-15

    Molecular docking is an important component of computer-aided drug discovery. In this communication, we describe GeauxDock, a new docking approach that builds on the ideas of ligand homology modeling. GeauxDock features a descriptor-based scoring function integrating evolutionary constraints with physics-based energy terms, a mixed-resolution molecular representation of protein-ligand complexes, and an efficient Monte Carlo sampling protocol. To drive docking simulations toward experimental conformations, the scoring function was carefully optimized to produce a correlation between the total pseudoenergy and the native-likeness of binding poses. Indeed, benchmarking calculations demonstrate that GeauxDock has a strong capacity to identify near-native conformations across docking trajectories with the area under receiver operating characteristics of 0.85. By excluding closely related templates, we show that GeauxDock maintains its accuracy at lower levels of homology through the increased contribution from physics-based energy terms compensating for weak evolutionary constraints. GeauxDock is available at http://www.institute.loni.org/lasigma/package/dock/. © 2015 Wiley Periodicals, Inc.

  9. 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.

  10. Using graphics processors to accelerate protein docking calculations.

    Science.gov (United States)

    Ritchie, David W; Venkatraman, Vishwesh; Mavridis, Lazaros

    2010-01-01

    Protein docking is the computationally intensive task of calculating the three-dimensional structure of a protein complex starting from the individual structures of the constituent proteins. In order to make the calculation tractable, most docking algorithms begin by assuming that the structures to be docked are rigid. This article describes some recent developments we have made to adapt our FFT-based "Hex" rigid-body docking algorithm to exploit the computational power of modern graphics processors (GPUs). The Hex algorithm is very efficient on conventional central processor units (CPUs), yet significant further speed-ups have been obtained by using GPUs. Thus, FFT-based docking calculations which formerly took many hours to complete using CPUs may now be carried out in a matter of seconds using GPUs. The Hex docking program and access to a server version of Hex on a GPU-based compute cluster are both available for public use.

  11. A Comparison of Candidate Seal Designs for Future Docking Systems

    Science.gov (United States)

    Dunlap, Patrick, H., Jr.; Steinetz, Bruce, M.

    2012-01-01

    NASA is developing a new docking system to support future space exploration missions to low Earth orbit, the Moon, and other destinations. A key component of this system is the seal at the main docking interface which inhibits the loss of cabin air once docking is complete. Depending on the mission, the seal must be able to dock in either a seal-on-flange or seal-on-seal configuration. Seal-on-flange mating would occur when a docking system equipped with a seal docks to a system with a flat metal flange. This would occur when a vehicle docks to a node on the International Space Station. Seal-on-seal mating would occur when two docking systems equipped with seals dock to each other. Two types of seal designs were identified for this application: Gask-O-seals and multi-piece seals. Both types of seals had a pair of seal bulbs to satisfy the redundancy requirement. A series of performance assessments and comparisons were made between the candidate seal designs indicating that they meet the requirements for leak rate and compression and adhesion loads under a range of operating conditions. Other design factors such as part count, integration into the docking system tunnel, seal-on-seal mating, and cost were also considered leading to the selection of the multi-piece seal design for the new docking system. The results of this study can be used by designers of future docking systems and other habitable volumes to select the seal design best-suited for their particular application.

  12. 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.

  13. Small-Angle X-ray Scattering Data in Combination with RosettaDock Improves the Docking Energy Landscape

    DEFF Research Database (Denmark)

    Sønderby, Pernille; Rinnan, Åsmund; Madsen, Jesper J.

    2017-01-01

    We have performed a benchmark to evaluate the relative success of using small-angle X-ray scattering (SAXS) data as constraints (hereafter termed SAXSconstrain) in the RosettaDock protocol (hereafter termed RosettaDockSAXS). For this purpose, we have chosen 38 protein complex structures, calculated...... the theoretical SAXS data for the protein complexes using the program CRYSOL, and then used the SAXS data as constraints. We further considered a few examples where crystal structures and experimental SAXS data are available. SAXSconstrain were added to the protocol in the initial, low-resolution docking step......-native protein complexes. The methodology used is based on rigid-body docking and works for cases where no or minor conformational changes occur upon binding of the docking partner. In a wider perspective, the strength of RosettaDockSAXS lies in the combination of low-resolution structural information on protein...

  14. Computational molecular docking studies on anticancer drugs

    Directory of Open Access Journals (Sweden)

    C. Baskaran

    2012-10-01

    Full Text Available Objective: Cancer can be described as the uncontrolled growth of abnormal cells. Lung cancer is one of the commonest malignant neoplasms all over the world. Oncogenic fusion genes consisting of EML4 and anaplastic lymphoma kinase (ALK are present in non-small-cell lung cancers, representing 2 to 7% of such tumors. ALK proteins play a vital role in deactivating the apoptosis process in cancer disease. Some of the most commonly used non-small-cell lung cancers drugs are Crizotinib, Sunitinibmalate, Tandutinib etc..., Non-small-cell lung cancer Cells need anaplastic lymphoma kinase (ALK to cell growth and proliferation the role of ALK in malignant proliferation and as a valid drug target. These drugs mainly work against the effects of ALK on these cells. Methods: The Protein- Ligand interaction plays a significant role in structural based drug designing. In our research work we have taken the Human anaplastic lymphoma kinase (ALK and the commercially available drugs against non-small-cell lung cancer. The ALK was docked to the above said drugs and the energy value obtained as follows Crizotinib(-9.86, Sunitinib malate(-8.26, Tandutinib(-8.05 using the Argus Lab docking software. Results: Depending on the energy values we have chosen the best two drugs they are Crizotinib(-9.86 and Sunitinib malate(-8.26. We tried to improve the binding efficiency and steric compatibility of the two drugs namely Crizotinib(-9.86 and Sunitinib malate(-8.26. Several modifications were made to the probable functional groups which were interacting with the receptor molecule. Analogs of this drug molecule were prepared using ACD ChemSketch and docked using Argus Lab docking software. Conclusions: Crizotinib Analog 2 and Sunitinib malate analog 1 were detected with significant energy values and probable lead molecules. The Modified drugs was sketched using Chemsketch were found to be better than the conventional drugs available. Further from this work we can improve the

  15. CABS-dock web server for the flexible docking of peptides to proteins without prior knowledge of the binding site.

    Science.gov (United States)

    Kurcinski, Mateusz; Jamroz, Michal; Blaszczyk, Maciej; Kolinski, Andrzej; Kmiecik, Sebastian

    2015-07-01

    Protein-peptide interactions play a key role in cell functions. Their structural characterization, though challenging, is important for the discovery of new drugs. The CABS-dock web server provides an interface for modeling protein-peptide interactions using a highly efficient protocol for the flexible docking of peptides to proteins. While other docking algorithms require pre-defined localization of the binding site, CABS-dock does not require such knowledge. Given a protein receptor structure and a peptide sequence (and starting from random conformations and positions of the peptide), CABS-dock performs simulation search for the binding site allowing for full flexibility of the peptide and small fluctuations of the receptor backbone. This protocol was extensively tested over the largest dataset of non-redundant protein-peptide interactions available to date (including bound and unbound docking cases). For over 80% of bound and unbound dataset cases, we obtained models with high or medium accuracy (sufficient for practical applications). Additionally, as optional features, CABS-dock can exclude user-selected binding modes from docking search or to increase the level of flexibility for chosen receptor fragments. CABS-dock is freely available as a web server at http://biocomp.chem.uw.edu.pl/CABSdock. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. effects of tail docking on fattening performance and carcass ...

    African Journals Online (AJOL)

    *

    Meat production from sheep has retained its importance for centuries in the economy as well as its role in human nutrition in ... The practice of docking lambs by various methods is used in order to obtain preferred products. Tails are removed using a knife, rubber elastrator ring or the hot tail docking iron. Peers et al. (2002) ...

  17. Orbital docking system centerline color television camera system test

    Science.gov (United States)

    Mongan, Philip T.

    1993-01-01

    A series of tests was run to verify that the design of the centerline color television camera (CTVC) system is adequate optically for the STS-71 Space Shuttle Orbiter docking mission with the Mir space station. In each test, a mockup of the Mir consisting of hatch, docking mechanism, and docking target was positioned above the Johnson Space Center's full fuselage trainer, which simulated the Orbiter with a mockup of the external airlock and docking adapter. Test subjects viewed the docking target through the CTVC under 30 different lighting conditions and evaluated target resolution, field of view, light levels, light placement, and methods of target alignment. Test results indicate that the proposed design will provide adequate visibility through the centerline camera for a successful docking, even with a reasonable number of light failures. It is recommended that the flight deck crew have individual switching capability for docking lights to provide maximum shadow management and that centerline lights be retained to deal with light failures and user preferences. Procedures for light management should be developed and target alignment aids should be selected during simulated docking runs.

  18. Changes in tail length between docking and weaning of lambs

    Science.gov (United States)

    This study was conducted with crossbred lambs (n = 109 female and 120 male) to quantify tail length at docking and weaning. Lambs were born in April of one year and weaned at ˜ 125 d of age. Within 24 h after birth, lambs were weighed and ear tagged, and rubber rings were applied to dock tails. R...

  19. The effects of docking on performance and carcass characteristics of ...

    African Journals Online (AJOL)

    The effects of tail docking at birth on growth performance and carcass characteristics of fat-tailed male Karakas lambs were investigated. A total of 23 Karakas single-born male lambs was used in this study. Nine were docked at one day of age using rubber elastrator rings and the rest was left intact. After weaning, the lambs ...

  20. 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. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Dock GEFs and their therapeutic potential: neuroprotection and axon regeneration.

    Science.gov (United States)

    Namekata, Kazuhiko; Kimura, Atsuko; Kawamura, Kazuto; Harada, Chikako; Harada, Takayuki

    2014-11-01

    The dedicator of cytokinesis (Dock) family is composed of atypical guanine exchange factors (GEFs) that activate the Rho GTPases Rac1 and Cdc42. Rho GTPases are best documented for their roles in actin polymerization and they regulate important cellular functions, including morphogenesis, migration, neuronal development, and cell division and adhesion. To date, 11 Dock family members have been identified and their roles have been reported in diverse contexts. There has been increasing interest in elucidating the roles of Dock proteins in recent years and studies have revealed that they are potential therapeutic targets for various diseases, including glaucoma, Alzheimer's disease, cancer, attention deficit hyperactivity disorder and combined immunodeficiency. Among the Dock proteins, Dock3 is predominantly expressed in the central nervous system and recent studies have revealed that Dock3 plays a role in protecting retinal ganglion cells from neurotoxicity and oxidative stress as well as in promoting optic nerve regeneration. In this review, we discuss the current understanding of the 11 Dock GEFs and their therapeutic potential, with a particular focus on Dock3 as a novel target for the treatment of glaucoma and other neurodegenerative diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

  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

  3. Reducing Seal Adhesion in Low Impact Docking Systems

    Science.gov (United States)

    Banks, Bruce A.; Miller, Sharon K.

    2010-01-01

    Silicone elastomers, used in seals for airlocks or other sealing surfaces in space, are sticky in their as-received condition. Because of the sticking, a greater force may be needed to separate the mating surfaces. If the adhesion is sufficiently high, a sudden unpredicted movement of the spacecraft during undocking, vibration, or uneven release could pull off the seal, resulting in a damage that would have to be repaired before another docking. The damaged seal can result in significant gas leakage and possibly in a catastrophic mishap impacting the safety of the crew. It is also possible that a compromised seal could result in a delayed but sudden gas leak that could put the crew at unexpected risk. This is especially of concern for androgynous seals, which have identical mating surfaces on both sides for interchangeability and redundancy. Such seals typically have elastomer-on-elastomer sealing surfaces. To reduce sticking, one could use release agents such as powders and lubricants, but these can be easily removed and transferred to other surfaces, causing uneven sealing and contamination. Modification of the elastomer surface to make a more slippery and less sticky surface that is integral with the bulk elastomer would be more desirable.

  4. A systematic analysis of scoring functions in rigid-body protein docking: The delicate balance between the predictive rate improvement and the risk of overtraining.

    Science.gov (United States)

    Barradas-Bautista, Didier; Moal, Iain H; Fernández-Recio, Juan

    2017-07-01

    Protein-protein interactions play fundamental roles in biological processes including signaling, metabolism, and trafficking. While the structure of a protein complex reveals crucial details about the interaction, it is often difficult to acquire this information experimentally. As the number of interactions discovered increases faster than they can be characterized, protein-protein docking calculations may be able to reduce this disparity by providing models of the interacting proteins. Rigid-body docking is a widely used docking approach, and is often capable of generating a pool of models within which a near-native structure can be found. These models need to be scored in order to select the acceptable ones from the set of poses. Recently, more than 100 scoring functions from the CCharPPI server were evaluated for this task using decoy structures generated with SwarmDock. Here, we extend this analysis to identify the predictive success rates of the scoring functions on decoys from three rigid-body docking programs, ZDOCK, FTDock, and SDOCK, allowing us to assess the transferability of the functions. We also apply set-theoretic measure to test whether the scoring functions are capable of identifying near-native poses within different subsets of the benchmark. This information can provide guides for the use of the most efficient scoring function for each docking method, as well as instruct future scoring functions development efforts. Proteins 2017; 85:1287-1297. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  5. Leukocyte-derived microvesicles dock on glomerular endothelial cells: stardust in the kidney.

    Science.gov (United States)

    Mack, Matthias

    2017-01-01

    Microvesicles are released from the plasma membrane of various cell types, can be taken up by other cells, and can transport membrane proteins and cytosolic contents between cells. Kahn et al. demonstrate that leukocyte-derived microvesicles bearing B1-kinin receptors are enriched in the plasma of vasculitis patients and dock on endothelial cells in the glomerulus. Cell culture experiments suggest that B1-receptors transferred by these microvesicles are functionally active on acceptor cells. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  6. Orbital Express fluid transfer demonstration system

    Science.gov (United States)

    Rotenberger, Scott; SooHoo, David; Abraham, Gabriel

    2008-04-01

    Propellant resupply of orbiting spacecraft is no longer in the realm of high risk development. The recently concluded Orbital Express (OE) mission included a fluid transfer demonstration that operated the hardware and control logic in space, bringing the Technology Readiness Level to a solid TRL 7 (demonstration of a system prototype in an operational environment). Orbital Express (funded by the Defense Advanced Research Projects Agency, DARPA) was launched aboard an Atlas-V rocket on March 9th, 2007. The mission had the objective of demonstrating technologies needed for routine servicing of spacecraft, namely autonomous rendezvous and docking, propellant resupply, and orbital replacement unit transfer. The demonstration system used two spacecraft. A servicing vehicle (ASTRO) performed multiple dockings with the client (NextSat) spacecraft, and performed a variety of propellant transfers in addition to exchanges of a battery and computer. The fluid transfer and propulsion system onboard ASTRO, in addition to providing the six degree-of-freedom (6 DOF) thruster system for rendezvous and docking, demonstrated autonomous transfer of monopropellant hydrazine to or from the NextSat spacecraft 15 times while on orbit. The fluid transfer system aboard the NextSat vehicle was designed to simulate a variety of client systems, including both blowdown pressurization and pressure regulated propulsion systems. The fluid transfer demonstrations started with a low level of autonomy, where ground controllers were allowed to review the status of the demonstration at numerous points before authorizing the next steps to be performed. The final transfers were performed at a full autonomy level where the ground authorized the start of a transfer sequence and then monitored data as the transfer proceeded. The major steps of a fluid transfer included the following: mate of the coupling, leak check of the coupling, venting of the coupling, priming of the coupling, fluid transfer, gauging

  7. High performance transcription factor-DNA docking with GPU computing.

    Science.gov (United States)

    Wu, Jiadong; Hong, Bo; Takeda, Takako; Guo, Jun-Tao

    2012-06-21

    Protein-DNA docking is a very challenging problem in structural bioinformatics and has important implications in a number of applications, such as structure-based prediction of transcription factor binding sites and rational drug design. Protein-DNA docking is very computational demanding due to the high cost of energy calculation and the statistical nature of conformational sampling algorithms. More importantly, experiments show that the docking quality depends on the coverage of the conformational sampling space. It is therefore desirable to accelerate the computation of the docking algorithm, not only to reduce computing time, but also to improve docking quality. In an attempt to accelerate the sampling process and to improve the docking performance, we developed a graphics processing unit (GPU)-based protein-DNA docking algorithm. The algorithm employs a potential-based energy function to describe the binding affinity of a protein-DNA pair, and integrates Monte-Carlo simulation and a simulated annealing method to search through the conformational space. Algorithmic techniques were developed to improve the computation efficiency and scalability on GPU-based high performance computing systems. The effectiveness of our approach is tested on a non-redundant set of 75 TF-DNA complexes and a newly developed TF-DNA docking benchmark. We demonstrated that the GPU-based docking algorithm can significantly accelerate the simulation process and thereby improving the chance of finding near-native TF-DNA complex structures. This study also suggests that further improvement in protein-DNA docking research would require efforts from two integral aspects: improvement in computation efficiency and energy function design. We present a high performance computing approach for improving the prediction accuracy of protein-DNA docking. The GPU-based docking algorithm accelerates the search of the conformational space and thus increases the chance of finding more near

  8. Effects of tail docking on behavior of confined feedlot cattle.

    Science.gov (United States)

    Kroll, L K; Grooms, D L; Siegford, J M; Schweihofer, J P; Daigle, C L; Metz, K; Ladoni, M

    2014-10-01

    Tail tip injuries occur in some feedlot cattle housed in slatted-floor facilities typically found in the midwestern United States. The practice of tail docking cattle on entry into these feedlot facilities was initiated to prevent tail injuries. Tail docking is a welfare concern from the standpoint that an important method of fly avoidance is removed and the tail docking procedure is painful and often excludes local anesthesia or extended analgesia. The primary objective of this study was to describe the behavioral responses of feedlot cattle following tail docking. Thirty-six heifers were randomly assigned to 1 of 2 treatment groups: docked (DK) or control (CN). All calves received an epidural following surgical preparation of the sacrococcygeal area and postoperative intravenous flunixin meglumine. A portion of the tail of DK calves was removed using pruning shears. An elastrator band was placed near the tail tip for hemostasis and tail tips were sprayed with fly spray. IceQube accelerometers collected step counts, motion index, lying time, lying bouts, and lying bout duration during d -4 through 13. Direct observations of cattle behavior were performed on d 0, 1, and 2. Step counts of DK calves were increased (P tail docking, DK calves had increased lying bouts per hour (1.7 vs. 0.9 on d 0; P tails more (P tail-docked feedlot cattle. We recommend that alternative strategies to reduce tail tip injury be explored.

  9. Ligand- and receptor-based docking with LiBELa

    Science.gov (United States)

    dos Santos Muniz, Heloisa; Nascimento, Alessandro S.

    2015-08-01

    Methodologies on molecular docking are constantly improving. The problem consists on finding an optimal interplay between the computational cost and a satisfactory physical description of ligand-receptor interaction. In pursuit of an advance in current methods we developed a mixed docking approach combining ligand- and receptor-based strategies in a docking engine, where tridimensional descriptors for shape and charge distribution of a reference ligand guide the initial placement of the docking molecule and an interaction energy-based global minimization follows. This hybrid docking was evaluated with soft-core and force field potentials taking into account ligand pose and scoring. Our approach was found to be competitive to a purely receptor-based dock resulting in improved logAUC values when evaluated with DUD and DUD-E. Furthermore, the smoothed potential as evaluated here, was not advantageous when ligand binding poses were compared to experimentally determined conformations. In conclusion we show that a combination of ligand- and receptor-based strategy docking with a force field energy model results in good reproduction of binding poses and enrichment of active molecules against decoys. This strategy is implemented in our tool, LiBELa, available to the scientific community.

  10. Ligand- and receptor-based docking with LiBELa.

    Science.gov (United States)

    dos Santos Muniz, Heloisa; Nascimento, Alessandro S

    2015-08-01

    Methodologies on molecular docking are constantly improving. The problem consists on finding an optimal interplay between the computational cost and a satisfactory physical description of ligand-receptor interaction. In pursuit of an advance in current methods we developed a mixed docking approach combining ligand- and receptor-based strategies in a docking engine, where tridimensional descriptors for shape and charge distribution of a reference ligand guide the initial placement of the docking molecule and an interaction energy-based global minimization follows. This hybrid docking was evaluated with soft-core and force field potentials taking into account ligand pose and scoring. Our approach was found to be competitive to a purely receptor-based dock resulting in improved logAUC values when evaluated with DUD and DUD-E. Furthermore, the smoothed potential as evaluated here, was not advantageous when ligand binding poses were compared to experimentally determined conformations. In conclusion we show that a combination of ligand- and receptor-based strategy docking with a force field energy model results in good reproduction of binding poses and enrichment of active molecules against decoys. This strategy is implemented in our tool, LiBELa, available to the scientific community.

  11. Molecular docking study of Papaver alkaloids to some alkaloid receptors

    Directory of Open Access Journals (Sweden)

    A. Nofallah

    2017-11-01

    Full Text Available Background and objectives: More than 40 different alkaloids have been obtained from opium the most important of which are morphine, codeine, papaverine, noscapine and tabaine. Opioid alkaloids produce analgesia by affecting areas of the brain that have peptides with pharmacological pseudo-opioid properties. These alkaloids show important effects on some intracellular peptides like mu, delta, and kappa receptors. Therefore, studying the effects of these alkaloids on different receptors is essential. Methods: Molecular docking is a well-known method in exploring the protein-ligand interactions. In this research, five important alkaloids were docked to crystal structure of human mu opioid receptor (4DKL, human delta opioid receptor (4EJ4 and human kappa opioid receptor (4DJH which were retrieved from protein databank. The 3D-structures of alkaloids were drawn by chembiooffice2010 and minimized with hyperchem package and submitted to molecular docking utilizing autodock-vina. Flexibility of the proteins was considered. The docking studies were performed to compare the affinity of these five alkaloids to the mentioned receptors. Results: We computationally docked each alkaloid compound onto each receptor structure and estimated their binding affinity based on dock scores. Dock score is a criteria including binding energy which utilized here for prediction and comparison of the binding affinities. Binding interactions of the docked alkaloids in receptor pockets were also visually inspected and compared. Conclusion: In this approach, using docking study as a computational method provided a valuable insight of opioid receptor pocket structures which would be essential to design more efficient drugs in pain managements and addiction treatments.

  12. 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.

  13. [Reference Intervals of Standard Test Items in Ningen Dock Examination].

    Science.gov (United States)

    Yamakado, Minoru

    2016-03-01

    Reference intervals (RIs) were derived from records of 1,499,288 individuals who underwent ningen dock examination in 188 institutes which belong to Japan Society of Ningen Dock in 2012. Targets were 27 basic laboratory tests, including the body mass index (BMI) and systolic and diastolic blood pressures (SBP, DBP). Individuals fulfilling strict criteria were chosen: SBP dock results will enable the appropriate interpretation of test results in health screening, and promote the effective application of CDLs for therapeutic intervention, taking into account the sex, age, and other health attributes.

  14. High-resolution global peptide-protein docking using fragments-based PIPER-FlexPepDock.

    Science.gov (United States)

    Alam, Nawsad; Goldstein, Oriel; Xia, Bing; Porter, Kathryn A; Kozakov, Dima; Schueler-Furman, Ora

    2017-12-01

    Peptide-protein interactions contribute a significant fraction of the protein-protein interactome. Accurate modeling of these interactions is challenging due to the vast conformational space associated with interactions of highly flexible peptides with large receptor surfaces. To address this challenge we developed a fragment based high-resolution peptide-protein docking protocol. By streamlining the Rosetta fragment picker for accurate peptide fragment ensemble generation, the PIPER docking algorithm for exhaustive fragment-receptor rigid-body docking and Rosetta FlexPepDock for flexible full-atom refinement of PIPER docked models, we successfully addressed the challenge of accurate and efficient global peptide-protein docking at high-resolution with remarkable accuracy, as validated on a small but representative set of peptide-protein complex structures well resolved by X-ray crystallography. Our approach opens up the way to high-resolution modeling of many more peptide-protein interactions and to the detailed study of peptide-protein association in general. PIPER-FlexPepDock is freely available to the academic community as a server at http://piperfpd.furmanlab.cs.huji.ac.il.

  15. High-resolution global peptide-protein docking using fragments-based PIPER-FlexPepDock.

    Directory of Open Access Journals (Sweden)

    Nawsad Alam

    2017-12-01

    Full Text Available Peptide-protein interactions contribute a significant fraction of the protein-protein interactome. Accurate modeling of these interactions is challenging due to the vast conformational space associated with interactions of highly flexible peptides with large receptor surfaces. To address this challenge we developed a fragment based high-resolution peptide-protein docking protocol. By streamlining the Rosetta fragment picker for accurate peptide fragment ensemble generation, the PIPER docking algorithm for exhaustive fragment-receptor rigid-body docking and Rosetta FlexPepDock for flexible full-atom refinement of PIPER docked models, we successfully addressed the challenge of accurate and efficient global peptide-protein docking at high-resolution with remarkable accuracy, as validated on a small but representative set of peptide-protein complex structures well resolved by X-ray crystallography. Our approach opens up the way to high-resolution modeling of many more peptide-protein interactions and to the detailed study of peptide-protein association in general. PIPER-FlexPepDock is freely available to the academic community as a server at http://piperfpd.furmanlab.cs.huji.ac.il.

  16. Dock6, a Dock-C subfamily guanine nucleotide exchanger, has the dual specificity for Rac1 and Cdc42 and regulates neurite outgrowth.

    Science.gov (United States)

    Miyamoto, Yuki; Yamauchi, Junji; Sanbe, Atsushi; Tanoue, Akito

    2007-02-15

    Small GTPases of the Rho family, Rho, Rac, and Cdc42, are critical regulators of the changes in the actin cytoskeleton. Rho GTPases are typically activated by Dbl-homology (DH)-domain-containing guanine nucleotide exchange factors (GEFs). Recent genetic and biochemical studies revealed a new type of GEF for the Rho GTPases. This family is composed of 11 genes, designated as Dock1 to Dock11, and is structurally divided into four classes Dock-A, -B, -C, and -D. Dock-A and -B subfamilies are typically GEFs specific for Rac1, while the Dock-D subfamily is specific for Cdc42. Here we show that Dock6, a member of the Dock-C subfamily, exchanges GDP for GTP for Rac1 and Cdc42 in vitro and in vivo. Furthermore, we find that, in mouse N1E-115 neuroblastoma cells, expression of Dock6 is increased following differentiation. Transfection of the catalytic Dock Homology Region-2 (DHR-2) domain of Dock6 promotes neurite outgrowth mediated by Rac1 and Cdc42. Conversely, knockdown of endogenous Dock6 by small interference RNA reduces activation of Rac1 and Cdc42 and neurite outgrowth. Taken together, these results suggest that Dock6 differs from all of the identified Dock180-related proteins, in that it is the GEF specific for both Rac1 and Cdc42 and may be one of physiological regulators of neurite outgrowth.

  17. 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...

  18. Photonic correlator pattern recognition: Application to autonomous docking

    Science.gov (United States)

    Sjolander, Gary W.

    1991-01-01

    Optical correlators for real-time automatic pattern recognition applications have recently become feasible due to advances in high speed devices and filter formulation concepts. The devices are discussed in the context of their use in autonomous docking.

  19. 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...

  20. Synthesis, biological evaluation and molecular docking studies of ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Chemical Sciences; Volume 128; Issue 6. Synthesis, biological evaluation and molecular docking studies of some novel cyclopropane carbohydrazide derivatives as potential anticancer agents. PONNAPALLI VEERABHADRA SWAMY PULLAIAH CHINA KAMBHAMPATI KOTHAPALLI BONNOTH ...

  1. FPGA acceleration of rigid-molecule docking codes

    Science.gov (United States)

    Sukhwani, B.; Herbordt, M.C.

    2011-01-01

    Modelling the interactions of biological molecules, or docking, is critical both to understanding basic life processes and to designing new drugs. The field programmable gate array (FPGA) based acceleration of a recently developed, complex, production docking code is described. The authors found that it is necessary to extend their previous three-dimensional (3D) correlation structure in several ways, most significantly to support simultaneous computation of several correlation functions. The result for small-molecule docking is a 100-fold speed-up of a section of the code that represents over 95% of the original run-time. An additional 2% is accelerated through a previously described method, yielding a total acceleration of 36× over a single core and 10× over a quad-core. This approach is found to be an ideal complement to graphics processing unit (GPU) based docking, which excels in the protein–protein domain. PMID:21857870

  2. Modeling and testing of docking and berthing mechanisms

    Science.gov (United States)

    Hall, Drew P.; Slone, B. Mark; Tobbe, Patrick A.

    2006-05-01

    The Contact Dynamics Simulation Laboratory (CDSL) of the Marshall Space Flight Center provides for refined hardware-in-the-loop real-time simulation of docking and berthing mechanisms and associated control systems. This facility is employed to verify the performance of docking/berthing mechanisms during Earth-orbit operations, determine the capture envelope of docking/berthing devices, measure contact loads at vehicle interfaces, and evaluate visual cues for man-in-the-loop operations. The CDSL has developed test verified analytical models of such systems as the International Space Station (ISS) Common Berthing Mechanism (CBM) and the Hubble Space Telescope (HST) Three Point Docking Mechanism. This paper will describe the modeling and test techniques employed at the CDSL and present results from recent programs.

  3. Functional and catalytic active sites prediction and docking analysis ...

    African Journals Online (AJOL)

    Bioinformatics

    2015-07-01

    Jul 1, 2015 ... docking analysis of azoreductase enzyme in. Pseudomonas putida with a variety of commercially available azodyes. Bikash Thakuria, Chandra J Singha, Premchand Maisnam and Samrat Adhikari*. Bioinformatics Centre, Department of Biotechnology, St. Edmund's College, Shillong, Meghalaya, India.

  4. Fault-Tolerant Relative Navigation System (RNS) for Docking Project

    Data.gov (United States)

    National Aeronautics and Space Administration — A method is propsed to develop a sensor fusion process for blending GPS/IMU/EO data for fault tolerant rendezvous and docking of spacecraft. The methodology takes...

  5. GPU Optimizations for a Production Molecular Docking Code*

    OpenAIRE

    Landaverde, Raphael; Herbordt, Martin C.

    2014-01-01

    Modeling molecular docking is critical to both understanding life processes and designing new drugs. In previous work we created the first published GPU-accelerated docking code (PIPER) which achieved a roughly 5× speed-up over a contemporaneous 4 core CPU. Advances in GPU architecture and in the CPU code, however, have since reduced this relalative performance by a factor of 10. In this paper we describe the upgrade of GPU PIPER. This required an entire rewrite, including algorithm changes a...

  6. Exponential Repulsion Improves Structural Predictability of Molecular Docking

    Czech Academy of Sciences Publication Activity Database

    Bazgier, Václav; Berka, K.; Otyepka, M.; Banáš, P.

    2016-01-01

    Roč. 37, č. 28 (2016), s. 2485-2494 ISSN 0192-8651 Institutional support: RVO:61389030 Keywords : cyclin-dependent kinases * structure-based design * scoring functions * cdk2 inhibitors * force-field * ligand interactions * drug discovery * purine * potent * protein-kinase-2 * molecular docking * dock 6.6 * drug design * cyclin-dependent kinase 2 * directory of decoys Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.229, year: 2016

  7. A primer on wood as dock construction material

    Science.gov (United States)

    Stan Lebow

    2007-01-01

    To be a successful marina owner and operator, it’s important to understand all the facets of one’s facility, including the intricacies of one part of the marina that most boaters take for granted: the docks. When it comes to dock construction, marinas have a wide-range of materials to choose from, with one of the most commonly used materials being preservative-treated...

  8. Demonstration of automated proximity and docking technologies

    Science.gov (United States)

    Anderson, Robert L.; Tsugawa, Roy K.; Bryan, Thomas C.

    1991-01-01

    An autodock was demonstrated using straightforward techniques and real sensor hardware. A simulation testbed was established and validated. The sensor design was refined with improved optical performance and image processing noise mitigation techniques, and the sensor is ready for production from off-the-shelf components. The autonomous spacecraft architecture is defined. The areas of sensors, docking hardware, propulsion, and avionics are included in the design. The Guidance Navigation and Control architecture and requirements are developed. Modular structures suitable for automated control are used. The spacecraft system manager functions including configuration, resource, and redundancy management are defined. The requirements for autonomous spacecraft executive are defined. High level decisionmaking, mission planning, and mission contingency recovery are a part of this. The next step is to do flight demonstrations. After the presentation the following question was asked. How do you define validation? There are two components to validation definition: software simulation with formal and vigorous validation, and hardware and facility performance validated with respect to software already validated against analytical profile.

  9. Reactive Path Planning Approach for Docking Robots in Unknown Environment

    Directory of Open Access Journals (Sweden)

    Peng Cui

    2017-01-01

    Full Text Available Autonomous robots need to be recharged and exchange information with the host through docking in the long-distance tasks. Therefore, feasible path is required in the docking process to guide the robot and adjust its pose. However, when there are unknown obstacles in the work area, it becomes difficult to determine the feasible path for docking. This paper presents a reactive path planning approach named Dubins-APF (DAPF to solve the path planning problem for docking in unknown environment with obstacles. In this proposed approach the Dubins curves are combined with the designed obstacle avoidance potential field to plan the feasible path. Firstly, an initial path is planned and followed according to the configurations of the robot and the docking station. Then when the followed path is evaluated to be infeasible, the intermediate configuration is calculated as well as the replanned path based on the obstacle avoidance potential field. The robot will be navigated to the docking station with proper pose eventually via the DAPF approach. The proposed DAPF approach is efficient and does not require the prior knowledge about the environment. Simulation results are given to validate the effectiveness and feasibility of the proposed approach.

  10. Enabling Exploration Through the International Docking System Standard

    Science.gov (United States)

    Hatfield, Caris A.

    2011-01-01

    Human exploration missions beyond low earth orbit will likely require international cooperation in order to leverage limited resources. International standards can help enable cooperative missions by providing well understood, predefined interfaces allowing compatibility between unique spacecraft and systems. The International Space Station (ISS) partnership has developed a publically available International Docking System Standard (IDSS) that provides a solution to one of these key interfaces by defining a common docking interface. The docking interface provides a way for even dissimilar spacecraft to dock for exchange of crew and cargo, as well as enabling the assembly of large space systems. This paper provides an overview of the key attributes of the IDSS, an overview of the NASA Docking System (NDS), and the plans for updating the ISS with IDSS compatible interfaces. The NDS provides a state of the art, low impact docking system that will initially be made available to commercial crew and cargo providers. The ISS will be used to demonstrate the operational utility of the IDSS interface as a foundational technology for cooperative exploration.

  11. A protocol for CABS-dock protein-peptide docking driven by side-chain contact information.

    Science.gov (United States)

    Kurcinski, Mateusz; Blaszczyk, Maciej; Ciemny, Maciej Pawel; Kolinski, Andrzej; Kmiecik, Sebastian

    2017-08-18

    The characterization of protein-peptide interactions is a challenge for computational molecular docking. Protein-peptide docking tools face at least two major difficulties: (1) efficient sampling of large-scale conformational changes induced by binding and (2) selection of the best models from a large set of predicted structures. In this paper, we merge an efficient sampling technique with external information about side-chain contacts to sample and select the best possible models. In this paper we test a new protocol that uses information about side-chain contacts in CABS-dock protein-peptide docking. As shown in our recent studies, CABS-dock enables efficient modeling of large-scale conformational changes without knowledge about the binding site. However, the resulting set of binding sites and poses is in many cases highly diverse and difficult to score. As we demonstrate here, information about a single side-chain contact can significantly improve the prediction accuracy. Importantly, the imposed constraints for side-chain contacts are quite soft. Therefore, the developed protocol does not require precise contact information and ensures large-scale peptide flexibility in the broad contact area. The demonstrated protocol provides the extension of the CABS-dock method that can be practically used in the structure prediction of protein-peptide complexes guided by the knowledge of the binding interface.

  12. Status of GPCR modeling and docking as reflected by community-wide GPCR Dock 2010 assessment.

    Science.gov (United States)

    Kufareva, Irina; Rueda, Manuel; Katritch, Vsevolod; Stevens, Raymond C; Abagyan, Ruben

    2011-08-10

    The community-wide GPCR Dock assessment is conducted to evaluate the status of molecular modeling and ligand docking for human G protein-coupled receptors. The present round of the assessment was based on the recent structures of dopamine D3 and CXCR4 chemokine receptors bound to small molecule antagonists and CXCR4 with a synthetic cyclopeptide. Thirty-five groups submitted their receptor-ligand complex structure predictions prior to the release of the crystallographic coordinates. With closely related homology modeling templates, as for dopamine D3 receptor, and with incorporation of biochemical and QSAR data, modern computational techniques predicted complex details with accuracy approaching experimental. In contrast, CXCR4 complexes that had less-characterized interactions and only distant homology to the known GPCR structures still remained very challenging. The assessment results provide guidance for modeling and crystallographic communities in method development and target selection for further expansion of the structural coverage of the GPCR universe. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. The Performance of Several Docking Programs at Reproducing Protein–Macrolide-Like Crystal Structures

    Directory of Open Access Journals (Sweden)

    Alejandro Castro-Alvarez

    2017-01-01

    Full Text Available The accuracy of five docking programs at reproducing crystallographic structures of complexes of 8 macrolides and 12 related macrocyclic structures, all with their corresponding receptors, was evaluated. Self-docking calculations indicated excellent performance in all cases (mean RMSD values ≤ 1.0 and confirmed the speed of AutoDock Vina. Afterwards, the lowest-energy conformer of each molecule and all the conformers lying 0–10 kcal/mol above it (as given by Macrocycle, from MacroModel 10.0 were subjected to standard docking calculations. While each docking method has its own merits, the observed speed of the programs was as follows: Glide 6.6 > AutoDock Vina 1.1.2 > DOCK 6.5 >> AutoDock 4.2.6 > AutoDock 3.0.5. For most of the complexes, the five methods predicted quite correct poses of ligands at the binding sites, but the lower RMSD values for the poses of highest affinity were in the order: Glide 6.6 ≈ AutoDock Vina ≈ DOCK 6.5 > AutoDock 4.2.6 >> AutoDock 3.0.5. By choosing the poses closest to the crystal structure the order was: AutoDock Vina > Glide 6.6 ≈ DOCK 6.5 ≥ AutoDock 4.2.6 >> AutoDock 3.0.5. Re-scoring (AutoDock 4.2.6//AutoDock Vina, Amber Score and MM-GBSA improved the agreement between the calculated and experimental data. For all intents and purposes, these three methods are equally reliable.

  14. 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.

  15. Spectroscopy and molecular docking studies on the binding of propyl gallate to human serum albumin

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Guo-fei; Wang, Yu; Xi, Lei; Liu, Jin; Wang, Hao; Du, Lin-fang, E-mail: dulinfang@scu.edu.cn

    2015-03-15

    The interaction of propyl gallate (PG) with human serum albumin (HSA) was investigated by fluorescence, far-UV CD and FT-IR spectroscopic methods as well as molecular docking. Fluorescence emission spectra demonstrated that the HSA fluorescence was quenched by PG through static quenching and energy transfer with the binding constants in the order of 10{sup 5} L mol{sup −1}. The thermodynamic parameters (ΔH=−29.64 KJ mol{sup −1}, ΔS=2.7 J mol{sup −1} K{sup −1}) indicated that both hydrophobic force and hydrogen bond interactions played a leading role in the formation of PG–HSA complex. The results also showed the existence of a single binding site, which was located in subdomain IIA (site I) as revealed by molecular docking and competitive binding experiments. Molecular docking studies further showed the participation of several amino acids in PG–HSA complexation, which stabilized by H-bonding systems. The synchronous fluorescence spectra showed that the binding of drug caused the environment of tryptophan residues became more polar. FT-IR and CD spectroscopic further showed that drug complexation altered protein conformation by a major reduction of α-helix inducing a partial protein destabilization. - Highlights: • The interaction between propyl gallate and HSA has been investigated. • HSA fluorescence is quenched by propyl gallate through static quenching mechanism. • Both hydrophobic force and hydrogen bond play major role in the binding process. • Site I of the HSA is found to be the main binding site for propyl gallate. • The structure of HSA has been changed upon the interaction with propyl gallate.

  16. Olympic torch transfer

    Science.gov (United States)

    1996-01-01

    KSC Shuttle Operations Manager Loren J. Shriver (right) transfers the Olympic flame to KSC runner Joanne Maceo's torch at the top of Launch Pad 39A after he carried the Olympic torch to the top of the pad as his contribution to the July 7, 1996 KSC Olympic torch relay effort. Jon Granston of the Atlanta Committee for the Olympic Games (center) witnesses the exchange. Maceo then carried her lit torch down the concrete hard stand of the pad to pass the flame to another of the 20-member KSC runner team that participated in the KSC relay effort. The Olympic torch arrived at KSC at 1:40 p.m. and traveled a 20-mile course to the pad and then out to the KSC visitor Center. The Space Shuttle Atlantis is behind the trio, poised for the STS-79 mission, with will feature the fourth docking of the shuttle with the Russian Mir space station.

  17. 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.

  18. 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

    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......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...... Score System' (KISS), a more biochemically meaningful measure for evaluation of docking programs based on pose prediction accuracy....

  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. 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.

  1. STRaND-2: Visual inspection, proximity operations & nanosatellite docking

    Science.gov (United States)

    Bridges, C. P.; Taylor, B.; Horri, N.; Underwood, C. I.; Kenyon, S.; Barrera-Ars, J.; Pryce, L.; Bird, R.

    The Surrey Training Research and Nanosatellite Demonstrator (STRaND) programme has been success in identifying and creating a leading low-cost nanosatellite programme with advanced attitude and orbit control system (AOCS) and experimental computing platforms based on smart-phone technologies. The next demonstration capabilities, that provide a challenging mission to the existing STRaND platform, is to perform visual inspection, proximity operations and nanosatellite docking. Visual inspection is to be performed using a COTS LIDAR system to estimate range and pose under 100 m. Proximity operations are controlled using a comprehensive guidance, navigation and control (GNC) loop in a polar form of the Hills Clohessy Wiltshire (HCW) frame including J2 perturbations. And finally, nanosatellite docking is performed at under 30 cm using a series of tuned magnetic coils. This paper will document the initial experiments and calculations used to qualify LIDAR components, size the mission thrust and tank requirements, and air cushion table demonstrations of the docking mechanism.

  2. Flavin Charge Transfer Transitions Assist DNA Photolyase Electron Transfer

    Science.gov (United States)

    Skourtis, Spiros S.; Prytkova, Tatiana; Beratan, David N.

    2007-12-01

    This contribution describes molecular dynamics, semi-empirical and ab-initio studies of the primary photo-induced electron transfer reaction in DNA photolyase. DNA photolyases are FADH--containing proteins that repair UV-damaged DNA by photo-induced electron transfer. A DNA photolyase recognizes and binds to cyclobutatne pyrimidine dimer lesions of DNA. The protein repairs a bound lesion by transferring an electron to the lesion from FADH-, upon photo-excitation of FADH- with 350-450 nm light. We compute the lowest singlet excited states of FADH- in DNA photolyase using INDO/S configuration interaction, time-dependent density-functional, and time-dependent Hartree-Fock methods. The calculations identify the lowest singlet excited state of FADH- that is populated after photo-excitation and that acts as the electron donor. For this donor state we compute conformationally-averaged tunneling matrix elements to empty electron-acceptor states of a thymine dimer bound to photolyase. The conformational averaging involves different FADH--thymine dimer confromations obtained from molecular dynamics simulations of the solvated protein with a thymine dimer docked in its active site. The tunneling matrix element computations use INDO/S-level Green's function, energy splitting, and Generalized Mulliken-Hush methods. These calculations indicate that photo-excitation of FADH- causes a π→π* charge-transfer transition that shifts electron density to the side of the flavin isoalloxazine ring that is adjacent to the docked thymine dimer. This shift in electron density enhances the FADH--to-dimer electronic coupling, thus inducing rapid electron transfer.

  3. Laser space rendezvous and docking system study continuation

    Science.gov (United States)

    Adelman, S.; Heynau, H.; Levinson, S.; Weindling, F.

    1977-01-01

    Investigations were made of a configuration for a spaceborne laser radar (ladar) to meet the requirements for rendezvous and docking with a cooperative object in synchronous orbit. An analysis was completed of laser phase locking techniques, while experimental verification was made of pulse repetition frequency and resonant scanning control loops. Data measurements on a satellite mock-up were also made. The investigation supports the original contention that a rendezvous and docking ladar can be configured to offer a cost effective and reliable solution to envisioned space missions.

  4. Structure and substrate docking of a hydroxy(phenyl)pyruvate reductase from the higher plant Coleus blumei Benth.

    Science.gov (United States)

    Janiak, Verena; Petersen, Maike; Zentgraf, Matthias; Klebe, Gerhard; Heine, Andreas

    2010-05-01

    Hydroxy(phenyl)pyruvate reductase [H(P)PR] belongs to the family of D-isomer-specific 2-hydroxyacid dehydrogenases and catalyzes the reduction of hydroxyphenylpyruvates as well as hydroxypyruvate and pyruvate to the corresponding lactates. Other non-aromatic substrates are also accepted. NADPH is the preferred cosubstrate. The crystal structure of the enzyme from Coleus blumei (Lamiaceae) has been determined at 1.47 A resolution. In addition to the apoenzyme, the structure of a complex with NADP(+) was determined at a resolution of 2.2 A. H(P)PR is a dimer with a molecular mass of 34 113 Da per subunit. The structure is similar to those of other members of the enzyme family and consists of two domains separated by a deep catalytic cleft. To gain insights into substrate binding, several compounds were docked into the cosubstrate complex structure using the program AutoDock. The results show two possible binding modes with similar docking energy. However, only binding mode A provides the necessary environment in the active centre for hydride and proton transfer during reduction, leading to the formation of the (R)-enantiomer of lactate and/or hydroxyphenyllactate.

  5. 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.

  6. Immune regulatory functions of DOCK family proteins in health and disease.

    Science.gov (United States)

    Nishikimi, Akihiko; Kukimoto-Niino, Mutsuko; Yokoyama, Shigeyuki; Fukui, Yoshinori

    2013-09-10

    DOCK proteins constitute a family of evolutionarily conserved guanine nucleotide exchange factors (GEFs) for Rho family of GTPases. Although DOCK family proteins do not contain the Dbl homology domain typically found in GEFs, they mediate the GTP-GDP exchange reaction through DHR-2 domain. Accumulating evidence indicates that the DOCK proteins act as major GEFs in varied biological settings. For example, DOCK2, which is predominantly expressed in hematopoietic cells, regulates migration and activation of leukocytes through Rac activation. On the other hand, it was recently reported that mutations of DOCK8, another member of the DOCK family proteins, cause a combined immunodeficiency syndrome in humans. This article reviews the structure, functions and signaling of DOCK2 and DOCK8, especially focusing on their roles in immune responses. © 2013 Elsevier Inc. All rights reserved.

  7. 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

  8. 48 CFR 52.247-40 - Ex Dock, Pier, or Warehouse, Port of Importation.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Ex Dock, Pier, or... Provisions and Clauses 52.247-40 Ex Dock, Pier, or Warehouse, Port of Importation. As prescribed in 47.303-12(c), insert the following clause in solicitations and contracts when the delivery term is ex dock...

  9. Synchronization in cross-docking networks : A research classification and framework

    NARCIS (Netherlands)

    Buijs, Paul; Vis, Iris F. A.; Carlo, Hector J.

    2014-01-01

    Cross-docking is a distribution strategy that enables the consolidation of less-than-truckload shipments into full truckloads without long-term storage. Due to the absence of a storage buffer inside a cross-dock, local and network-wide cross-docking operations need to be carefully synchronized. This

  10. 19 CFR 18.24 - Retention of goods on dock; splitting of shipments.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Retention of goods on dock; splitting of shipments... Transit Through the United States to Foreign Countries § 18.24 Retention of goods on dock; splitting of... dock, the port director, in his discretion, may allow in-transit merchandise, including merchandise...

  11. Synthesis, docking and anticancer activity studies of D-proline ...

    Indian Academy of Sciences (India)

    D-proline-incorporated wainunuamide — a cyclic octapeptide was synthesized and characterized by FTIR, 1H and 13C NMR and Mass spectral analysis. Molecular docking studies were carried out for the designed cyclic octapeptide and the results showed greater affinity for HPV18-2IOI receptor (HeLa cancer cell line).

  12. Synthesis, docking and anticancer activity studies of D-proline ...

    Indian Academy of Sciences (India)

    Synthesis, docking and anticancer activity studies of D-proline-incorporated wainunuamide. M HIMAJAa,∗, A RANJITHAa and SUNIL V MALIb. aSchool of Advanced Sciences, Pharmaceutical Chemistry Division, VIT University, Vellore 632 014, India. bMedicinal Chemistry Division, Piramal Life Science Ltd., Mumbai 400 ...

  13. 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 de...

  14. Tail docking in dogs: can attitude change be achieved?

    Science.gov (United States)

    Bennett, P; Perini, E

    2003-05-01

    The debate about tail docking in domestic dogs continues to rage in many developed countries and attitudes expressed by different community groups remain diametrically opposed. Veterinary associations and welfare organisations typically want the practice banned, while many breeders and pure-bred dog associations just as vigorously oppose the introduction of anti-docking legislation. In recent years, much data have been accumulated concerning the welfare implications of tail docking. A recent evaluation of this literature suggests that the practice has little to recommend it and that, in the absence of reasonable case-by-case justification, it may constitute an unacceptable abuse of a sentient species. Given this situation, it is difficult to understand why many canine interest groups, presumably representing those people who care most about the welfare of companion dogs, should continue to hold such strong attitudes in favour of tail docking. In this review we attempt to explain why different community groups might espouse strong but opposing attitudes, despite having access to the same information. We argue that the theory of cognitive dissonance, popular among social psychologists, may provide a useful framework within which to understand, and attempt to alter, attitudes that persist even though they appear contrary to available empirical evidence.

  15. Synthesis and molecular docking of new hydrazones derived from ...

    African Journals Online (AJOL)

    Synthesis and molecular docking of new hydrazones derived from ethyl isonipecotate and their biological activities. A Munir, Aziz-ur Rehman, M.A. Abbasi, S.Z. Siddiqui, A Nasir, S.G. Khan, S Rasool, S.A.A. Shah ...

  16. Design of a Docking Wall-Climbing Robot

    Directory of Open Access Journals (Sweden)

    Rong Liu

    2013-02-01

    Full Text Available This paper introduces an innovative wall-climbing robot. The robot consists of two single-body negative pressure adsorption robots which could dock together as a mother-robot or separate into two independent child-robots. The child-robots connect with each other through a docking mechanism which can not only lock solidly and unlock smoothly but which can also adjust the relative position of the two child-robots. This design guarantees that while in dock mode the mother robot will be able to cross some barriers which are impossible to surmount for a single-body wall-climbing robot, while in separate mode the child-robots maintain agility and mobility compared to other two-body robots. In this paper, an overview of the mechanical structure of the robot is first presented and then three possible mechanisms for barrier-crossing are discussed and a reasonable one is selected. An analysis of the initial docking condition of the selected design is also given which provides the basis for the experiments and research for the future.

  17. 18 CFR 1304.204 - Docks, piers, and boathouses.

    Science.gov (United States)

    2010-04-01

    ... pool. (e) All docks, piers, and other water-use facilities must be attached to the shore with a single walkway which must connect from land to the structure by the most direct route and must adjoin the access... shall not exceed six feet in width. (l) Enclosed space shall be used solely for storage of water-use...

  18. 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.

  19. 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...

  20. I-AUV Docking and Panel Intervention at Sea

    Science.gov (United States)

    Palomeras, Narcís; Peñalver, Antonio; Massot-Campos, Miquel; Negre, Pep Lluís; Fernández, José Javier; Ridao, Pere; Sanz, Pedro J.; Oliver-Codina, Gabriel

    2016-01-01

    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. PMID:27754348

  1. Molecular docking and in silico ADMET studies of silibinin and ...

    African Journals Online (AJOL)

    Q-Site Finder and admetSAR were employed for active site prediction and ADMET profile, respectively. Furthermore, protein-ligand complexes were visually inspected by LigPlot and Chimera. Results: Post-docking analysis confirmed strong interaction of silibinin and glycyrrhetic acid with their respective targets. ADMET ...

  2. Molecular Dynamics and Docking of Biphenyl: A Potential ...

    African Journals Online (AJOL)

    Purpose: To develop a new drug that inhibits viral attachment and entry for the treatment of HIV/AIDS patients. Methods: Two Protein Databank (PDB) crystal structures of HIV-1 gp120-CD4 complexes, namely,. 1RZK and 1G9N, were mutated at amino acid position 43 to a biphenylalanine (biPhe-43) residue. FireDock web ...

  3. 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.

  4. 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.

  5. 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.

  6. ConsDock: A new program for the consensus analysis of protein-ligand interactions.

    Science.gov (United States)

    Paul, Nicodème; Rognan, Didier

    2002-06-01

    Protein-based virtual screening of chemical libraries is a powerful technique for identifying new molecules that may interact with a macromolecular target of interest. Because of docking and scoring limitations, it is more difficult to apply as a lead optimization method because it requires that the docking/scoring tool is able to propose as few solutions as possible and all of them with a very good accuracy for both the protein-bound orientation and the conformation of the ligand. In the present study, we present a consensus docking approach (ConsDock) that takes advantage of three widely used docking tools (Dock, FlexX, and Gold). The consensus analysis of all possible poses generated by several docking tools is performed sequentially in four steps: (i) hierarchical clustering of all poses generated by a docking tool into families represented by a leader; (ii) definition of all consensus pairs from leaders generated by different docking programs; (iii) clustering of consensus pairs into classes, represented by a mean structure; and (iv) ranking the different means starting from the most populated class of consensus pairs. When applied to a test set of 100 protein-ligand complexes from the Protein Data Bank, ConsDock significantly outperforms single docking with respect to the docking accuracy of the top-ranked pose. In 60% of the cases investigated here, ConsDock was able to rank as top solution a pose within 2 A RMSD of the X-ray structure. It can be applied as a postprocessing filter to either single- or multiple-docking programs to prioritize three-dimensional guided lead optimization from the most likely docking solution. Copyright 2002 Wiley-Liss, Inc.

  7. 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

    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...

  8. Docking of small molecules to farnesoid X receptors using AutoDock Vina with the Convex-PL potential: lessons learned from D3R Grand Challenge 2

    Science.gov (United States)

    Kadukova, Maria; Grudinin, Sergei

    2017-09-01

    The 2016 D3R Grand Challenge 2 provided an opportunity to test multiple protein-ligand docking protocols on a set of ligands bound to farnesoid X receptor that has many available experimental structures. We participated in the Stage 1 of the Challenge devoted to the docking pose predictions, with the mean RMSD value of our submission poses of 2.9 Å. Here we present a thorough analysis of our docking predictions made with AutoDock Vina and the Convex-PL rescoring potential by reproducing our submission protocol and running a series of additional molecular docking experiments. We conclude that a correct receptor structure, or more precisely, the structure of the binding pocket, plays the crucial role in the success of our docking studies. We have also noticed the important role of a local ligand geometry, which seems to be not well discussed in literature. We succeed to improve our results up to the mean RMSD value of 2.15-2.33 Å dependent on the models of the ligands, if docking these to all available homologous receptors. Overall, for docking of ligands of diverse chemical series we suggest to perform docking of each of the ligands to a set of multiple receptors that are homologous to the target.

  9. 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

  10. 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.

  11. More tail lesions among undocked than tail docked pigs in a conventional herd

    DEFF Research Database (Denmark)

    Lahrmann, H. P.; Busch, M. E.; D'Eath, R. B.

    2017-01-01

    The vast majority of piglets reared in the European Union (EU) and worldwide is tail docked to reduce the risk of being tail bitten, even though EU animal welfare legislation bans routine tail docking. Many conventional herds experience low levels of tail biting among tail docked pigs, however...... it is not known, what the prevalence would have been had the pigs not been tail docked. The aim of this study was to compare the prevalence of tail lesions between docked and undocked pigs in a conventional piggery in Denmark with very low prevalence of tail biting among tail docked pigs. The study included 1922...... that housing pigs with intact tails in conventional herds with very low prevalence of tail biting among tail docked pigs, will increase the prevalence of pigs with tail lesions considerably, and pig producers will need more hospital pens. Abattoir data indicate that tail biting remarks from meat inspection...

  12. The Mechanical Performance of Subscale Candidate Elastomer Docking Seals

    Science.gov (United States)

    Bastrzyk, Marta B.; Daniels, Christopher C.

    2010-01-01

    The National Aeronautics and Space Administration is developing a Low Impact Docking System (LIDS) for future exploration missions. The mechanism is a new state-of-the-art device for in-space assembly of structures and rendezvous of vehicles. At the interface between two pressurized modules, each with a version of the LIDS attached, a composite elastomer-metal seal assembly prevents the breathable air from escaping into the vacuum of space. Attached to the active LIDS, this seal mates against the passive LIDS during docking operation. The main interface seal assembly must exhibit low leak and outgas values, must be able to withstand various harsh space environments, must remain operational over a range of temperatures from -50 C to 75 C, and perform after numerous docking cycles. This paper presents results from a comprehensive study of the mechanical performance of four candidate subscale seal assembly designs at -50, 23, 50, and 75 C test temperatures. In particular, the force required to fully compress the seal during docking, and that which is required for separation during the undocking operation were measured. The height of subscale main interface seal bulbs, as well as the test temperature, were shown to have a significant effect on the forces the main interface seal of the LIDS may experience during docking and undocking operations. The average force values required to fully compress each of the seal assemblies were shown to increase with test temperature by approximately 50% from -50 to 75 C. Also, the required compression forces were shown to increase as the height of the seal bulb was increased. The seal design with the tallest elastomer seal bulb, which was 31% taller than that with the shortest bulb, required force values approximately 45% higher than those for the shortest bulb, independent of the test temperature. The force required to separate the seal was shown to increase with decreasing temperature after 15 hours of simulated docking. No adhesion

  13. Fast Docking on Graphics Processing Units via Ray-Casting

    Science.gov (United States)

    Khar, Karen R.; Goldschmidt, Lukasz; Karanicolas, John

    2013-01-01

    Docking Approach using Ray Casting (DARC) is structure-based computational method for carrying out virtual screening by docking small-molecules into protein surface pockets. In a complementary study we find that DARC can be used to identify known inhibitors from large sets of decoy compounds, and can identify new compounds that are active in biochemical assays. Here, we describe our adaptation of DARC for use on Graphics Processing Units (GPUs), leading to a speedup of approximately 27-fold in typical-use cases over the corresponding calculations carried out using a CPU alone. This dramatic speedup of DARC will enable screening larger compound libraries, screening with more conformations of each compound, and including multiple receptor conformations when screening. We anticipate that all three of these enhanced approaches, which now become tractable, will lead to improved screening results. PMID:23976948

  14. Molecular Dynamics and Docking of Biphenyl: A Potential ...

    African Journals Online (AJOL)

    FireDock revealed that electrostatic and Van der Waals interactions were mainly involved in the CD4-gp120 binding and helped to stabilize the protein interactions. In a 5ns MD simulation, biPhe-43 and Trp-43 mutated CD4 demonstrated best Gibbs free binding energies (-16271 „b 29 and -16266 ¡Ó 18 kJ/mol, ...

  15. 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.

  16. Synthesis, in vitro anti-inflammatory activity and molecular docking ...

    Indian Academy of Sciences (India)

    Synthesis, in vitro anti-inflammatory activity and molecular docking .... 2.2 Synthesis. 2.2a Synthesis of 2,3-bis (4-methoxy phenyl)-3-chloro-2- prop-2-ene aldehyde (2): 0.05 mol (7.66 g) of phosphorous oxychloride (POCl3) was added drop wise over a period of ...... a mechanism of action for aspirin-like drugs Nature 231.

  17. Insight Mechanism of the Selective Lanosterol Synthase Inhibitor: Molecular Modeling, Docking and Density Functional Theory Approaches.

    Science.gov (United States)

    Karunagaran, Subramanian; Kavitha, Rengarajan; Vadivelu, Muthu; Lee, Keun Woo; Meganathan, Chandrasekaran

    2017-11-10

    Lanosterol synthase (Oxidosqualene cyclase) is an enzyme, which plays a central role in cholesterol and sterols biosynthesis. Lanosterol synthase drugs are used to lower the level of cholesterol in the blood and treat wide variety of diseases like atherosclerosis, coronary heart diseases etc. There is a great interest in the identification of drugs that target this enzyme for anticholesteraemic agent using in silico tools. Ligand based pharmacophore model was developed using Discovery Studio 2.5. The best model was used as a tool to retrieve suitable molecule for Lanosterol synthase inhibitor from commercial database and Virtual screening of large commercially available databases to retrieve the best mole of Hypo1 using. Molecular docking was done using three different tools named as GOLD, GLIDE and AUTODOCK 4.0. Density functional theory approach and Density of State spectrum were carried out using Gaussian 09 and GAUSS SUM 3.0. Contribution of these methods in the selection of anticholesteraemic compounds has been discussed. The best pharmacophore model was used to screen the commercial database. Totally 8 compounds were showed with the best orientation, binding mode and binging energy in the docking analyses. The orbital energies such as HOMO, LUMO and DOS spectrum for 8 hit compounds showed the energy gap that results in charge transfer and stability in the active site region. The results showed that our 8 potent leads could serve for further findings. In silico approaches, our 8 hit compounds could serve as the better understanding to design the novel lanosterol synthase inhibitors as anticholesteraemic activity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. 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.

  19. An Approach to Mathematical Modeling and Estimation of Probe-Drogue Docking Success Probability for UAV Autonomous Aerial Refueling

    OpenAIRE

    Xufeng Wang; Jianmin Li; Xingwei Kong; Xinmin Dong; Bo Zhang

    2017-01-01

    One of the keys to the success of aerial refueling for probe-drogue aerial refueling system (PDARS) is the successful docking between the probe and drogue. The study of probe-drogue docking success probability offers an important support to achieving successful docking. During the docking phase of PDARS, based on prior information and reasonable assumptions for the movements of the drogue under atmospheric disturbance, the probe-drogue docking success probability is converted to the probabili...

  20. 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.

  1. Machine learning and docking models for Mycobacterium tuberculosis topoisomerase I.

    Science.gov (United States)

    Ekins, Sean; Godbole, Adwait Anand; Kéri, György; Orfi, Lászlo; Pato, János; Bhat, Rajeshwari Subray; Verma, Rinkee; Bradley, Erin K; Nagaraja, Valakunja

    2017-03-01

    There is a shortage of compounds that are directed towards new targets apart from those targeted by the FDA approved drugs used against Mycobacterium tuberculosis. Topoisomerase I (Mttopo I) is an essential mycobacterial enzyme and a promising target in this regard. However, it suffers from a shortage of known inhibitors. We have previously used computational approaches such as homology modeling and docking to propose 38 FDA approved drugs for testing and identified several active molecules. To follow on from this, we now describe the in vitro testing of a library of 639 compounds. These data were used to create machine learning models for Mttopo I which were further validated. The combined Mttopo I Bayesian model had a 5 fold cross validation receiver operator characteristic of 0.74 and sensitivity, specificity and concordance values above 0.76 and was used to select commercially available compounds for testing in vitro. The recently described crystal structure of Mttopo I was also compared with the previously described homology model and then used to dock the Mttopo I actives norclomipramine and imipramine. In summary, we describe our efforts to identify small molecule inhibitors of Mttopo I using a combination of machine learning modeling and docking studies in conjunction with screening of the selected molecules for enzyme inhibition. We demonstrate the experimental inhibition of Mttopo I by small molecule inhibitors and show that the enzyme can be readily targeted for lead molecule development. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Modeling of metal interaction geometries for protein-ligand docking.

    Science.gov (United States)

    Seebeck, Birte; Reulecke, Ingo; Kämper, Andreas; Rarey, Matthias

    2008-05-15

    The accurate modeling of metal coordination geometries plays an important role for structure-based drug design applied to metalloenzymes. For the development of a new metal interaction model, we perform a statistical analysis of metal interaction geometries that are relevant to protein-ligand complexes. A total of 43,061 metal sites of the Protein Data Bank (PDB), containing amongst others magnesium, calcium, zinc, iron, manganese, copper, cadmium, cobalt, and nickel, were evaluated according to their metal coordination geometry. Based on statistical analysis, we derived a model for the automatic calculation and definition of metal interaction geometries for the purpose of molecular docking analyses. It includes the identification of the metal-coordinating ligands, the calculation of the coordination geometry and the superposition of ideal polyhedra to identify the optimal positions for free coordination sites. The new interaction model was integrated in the docking software FlexX and evaluated on a data set of 103 metalloprotein-ligand complexes, which were extracted from the PDB. In a first step, the quality of the automatic calculation of the metal coordination geometry was analyzed. In 74% of the cases, the correct prediction of the coordination geometry could be determined on the basis of the protein structure alone. Secondly, the new metal interaction model was tested in terms of predicting protein-ligand complexes. In the majority of test cases, the new interaction model resulted in an improved docking accuracy of the top ranking placements. 2007 Wiley-Liss, Inc.

  3. In Silico Docking of HNF-1a Receptor Ligands

    Directory of Open Access Journals (Sweden)

    Gumpeny Ramachandra Sridhar

    2012-01-01

    Full Text Available Background. HNF-1a is a transcription factor that regulates glucose metabolism by expression in various tissues. Aim. To dock potential ligands of HNF-1a using docking software in silico. Methods. We performed in silico studies using HNF-1a protein 2GYP·pdb and the following softwares: ISIS/Draw 2.5SP4, ARGUSLAB 4.0.1, and HEX5.1. Observations. The docking distances (in angstrom units: 1 angstrom unit (Å = 0.1 nanometer or  metres with ligands in decreasing order are as follows: resveratrol (3.8 Å, aspirin (4.5 Å, stearic acid (4.9 Å, retinol (6.0 Å, nitrazepam (6.8 Å, ibuprofen (7.9 Å, azulfidine (9.0 Å, simvastatin (9.0 Å, elaidic acid (10.1 Å, and oleic acid (11.6 Å. Conclusion. HNF-1a domain interacted most closely with resveratrol and aspirin

  4. 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.

  5. GPU Optimizations for a Production Molecular Docking Code.

    Science.gov (United States)

    Landaverde, Raphael; Herbordt, Martin C

    2014-09-01

    Modeling molecular docking is critical to both understanding life processes and designing new drugs. In previous work we created the first published GPU-accelerated docking code (PIPER) which achieved a roughly 5× speed-up over a contemporaneous 4 core CPU. Advances in GPU architecture and in the CPU code, however, have since reduced this relalative performance by a factor of 10. In this paper we describe the upgrade of GPU PIPER. This required an entire rewrite, including algorithm changes and moving most remaining non-accelerated CPU code onto the GPU. The result is a 7× improvement in GPU performance and a 3.3× speedup over the CPU-only code. We find that this difference in time is almost entirely due to the difference in run times of the 3D FFT library functions on CPU (MKL) and GPU (cuFFT), respectively. The GPU code has been integrated into the ClusPro docking server which has over 4000 active users.

  6. GPU Optimizations for a Production Molecular Docking Code*

    Science.gov (United States)

    Landaverde, Raphael; Herbordt, Martin C.

    2015-01-01

    Modeling molecular docking is critical to both understanding life processes and designing new drugs. In previous work we created the first published GPU-accelerated docking code (PIPER) which achieved a roughly 5× speed-up over a contemporaneous 4 core CPU. Advances in GPU architecture and in the CPU code, however, have since reduced this relalative performance by a factor of 10. In this paper we describe the upgrade of GPU PIPER. This required an entire rewrite, including algorithm changes and moving most remaining non-accelerated CPU code onto the GPU. The result is a 7× improvement in GPU performance and a 3.3× speedup over the CPU-only code. We find that this difference in time is almost entirely due to the difference in run times of the 3D FFT library functions on CPU (MKL) and GPU (cuFFT), respectively. The GPU code has been integrated into the ClusPro docking server which has over 4000 active users. PMID:26594667

  7. 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. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Docking of the da Vinci Si Surgical System® with single-site technology.

    Science.gov (United States)

    Iranmanesh, Pouya; Morel, Philippe; Buchs, Nicolas C; Pugin, François; Volonte, Francesco; Kreaden, Usha Seshadri; Hagen, Monika E

    2013-03-01

    Strategies to spare operating room (OR) times are crucial to limiting the costs involved in robotic surgery. Among other factors, the pre-operative set-up and docking phases have been incriminated at first to be time consuming. The docking process on the standard multiport da Vinci Surgical System has not been shown to significantly prolong the overall OR time. This study aims to analyse whether the length of the docking process on the new da Vinci Si Surgical System with Single-Site™ technology remains acceptable. We prospectively analysed all of the robotic single-incision cholecystectomies performed at our institution for docking and operating times during 2011-2012. The docking task load was assessed each time in a self-administered fashion by the docking surgeon using the NASA TLX visual scale. Sixty-four robotic single-incision cholecystectomies were included and analysed. The mean operative time was 78 min. Two surgeons with previous robotic surgery experience and a group of three less experienced robotic surgeons were responsible for docking the system. They performed 45, 10 and nine dockings, respectively. The overall mean docking time was 6.4 min with no significant difference between the groups. The docking process represented approximately 8% of the operating time. The surgeon with the most procedures showed significant progress in his docking times. The different task load parameters did not show a statistical difference between the three groups, with the exception of the frustration parameter, which was higher in the group of less experienced surgeons. There were significant correlations between docking times and the assessment of the various task load parameters. The docking process for a robotic single-incision cholecystectomy is learned rapidly and does not significantly increase the overall OR time. Copyright © 2013 John Wiley & Sons, Ltd.

  9. Multiple factors confer specific Cdc42 and Rac protein activation by dedicator of cytokinesis (DOCK) nucleotide exchange factors.

    Science.gov (United States)

    Kulkarni, Kiran; Yang, Jing; Zhang, Ziguo; Barford, David

    2011-07-15

    DOCK (dedicator of cytokinesis) guanine nucleotide exchange factors (GEFs) activate the Rho-family GTPases Rac and Cdc42 to control cell migration, morphogenesis, and phagocytosis. The DOCK A and B subfamilies activate Rac, whereas the DOCK D subfamily activates Cdc42. Nucleotide exchange is catalyzed by a conserved DHR2 domain (DOCK(DHR2)). Although the molecular basis for DOCK(DHR2)-mediated GTPase activation has been elucidated through structures of a DOCK9(DHR2)-Cdc42 complex, the factors determining recognition of specific GTPases are unknown. To understand the molecular basis for DOCK-GTPase specificity, we have determined the crystal structure of DOCK2(DHR2) in complex with Rac1. DOCK2(DHR2) and DOCK9(DHR2) exhibit similar tertiary structures and homodimer interfaces and share a conserved GTPase-activating mechanism. Multiple structural differences between DOCK2(DHR2) and DOCK9(DHR2) account for their selectivity toward Rac1 and Cdc42. Key determinants of selectivity of Cdc42 and Rac for their cognate DOCK(DHR2) are a Phe or Trp residue within β3 (residue 56) and the ability of DOCK proteins to exploit differences in the GEF-induced conformational changes of switch 1 dependent on a divergent residue at position 27. DOCK proteins, therefore, differ from DH-PH GEFs that select their cognate GTPases through recognition of structural differences within the β2/β3 strands.

  10. 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.

  11. Transfer Pricing

    DEFF Research Database (Denmark)

    Nielsen, Søren Bo

    2014-01-01

    Against a background of rather mixed evidence about transfer pricing practices in multinational enterprises (MNEs) and varying attitudes on the part of tax authorities, this paper explores how multiple aims in transfer pricing can be pursued across four different transfer pricing regimes. A MNE h...

  12. 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.

  13. 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.

  14. Synaptotagmin-1 docks secretory vesicles to syntaxin-1/SNAP-25 acceptor complexes

    DEFF Research Database (Denmark)

    de Wit, Heidi; Walter, Alexander M; Milosevic, Ira

    2009-01-01

    to SNARE complex assembly. Here, using adrenal chromaffin cells, we identify the vesicular docking partner as synaptotagmin-1, the calcium sensor for exocytosis, and SNAP-25 as an essential plasma membrane docking factor, which, together with the previously known docking factors Munc18-1 and syntaxin, form...... the minimal docking machinery. Moreover, we show that the requirement for Munc18-1 in docking, but not fusion, can be overcome by stabilizing syntaxin/SNAP-25 acceptor complexes. These findings, together with cross-rescue, double-knockout, and electrophysiological data, lead us to propose that vesicles dock...... when synaptotagmin-1 binds to syntaxin/SNAP-25 acceptor complexes, whereas Munc18-1 is required for the downstream association of synaptobrevin to form fusogenic SNARE complexes....

  15. Casual dock work: profile of diseases and injuries and perception of influence on health.

    Science.gov (United States)

    Cezar-Vaz, Marta Regina; de Almeida, Marlise Capa Verde; Bonow, Clarice Alves; Rocha, Laurelize Pereira; Borges, Anelise Miritz; Piexak, Diéssica Roggia

    2014-02-19

    The present study aimed to identify the profile of diseases and injuries that affect casual dock workers and identify casual dock workers' perceptions of positive and negative work influences on their health. This study consisted of two phases. The first phase was a quantitative study composed of a retrospective analysis, conducted with 953 medical records. The second phase of the research is a non-random sample with 51 casual dock workers. Data analysis was performed with SPSS 19.0. The average age of the casual dock workers was 48.7. Concerning working time, the majority had more than 19.6 years of dock work experience. In the first phase, 527 pathologic diagnoses were identified. The diagnoses that affected the musculoskeletal system (15.8%, N = 152; p dock work perception and have motivated an introduction of preventive measures.

  16. Parallel side-docking technique for gynecologic procedures utilizing the da Vinci robot.

    Science.gov (United States)

    Silverman, Suzanne; Orbuch, Laurence; Orbuch, Iris

    2012-09-01

    Minimally invasive approaches to gynecologic surgery have quickly gained favor. The da Vinci surgical system robot as an option for minimally invasive surgery offers many advantages. As the placement of the system between the legs can be prohibitive, we propose a modification of the standard docking procedure by aligning the system parallel to the operating room table. Our experience is that parallel side-docking allows access to the perineum without compromising docking time and range of motion.

  17. Interaction of the minocycline with extracelluar protein and intracellular protein by multi-spectral techniques and molecular docking

    Science.gov (United States)

    Fang, Qing; Wang, Yirun; Hu, Taoying; Liu, Ying

    2017-02-01

    The interaction of minocyeline (MNC) with extracelluar protein (lysozyme, LYSO) or intracellular protein (bovine hemoglobin, BHb) was investigated using multi-spectral techniques and molecular docking in vitro. Fluorescence studies suggested that MNC quenched LYSO/BHb fluorescence in a static mode with binding constants of 2.01 and 0.26 × 104 L•mol-1 at 298 K, respectively. The LYZO-MNC system was more easily influenced by temperature (298 and 310 K) than the BHb-MNC system. The thermodynamic parameters demonstrated that hydrogen bonds and van der Waals forces played the major role in the binding process. Based on the Förster theory of nonradiative energy transfer, the binding distances between MNC and the inner tryptophan residues of LYSO and BHb were calculated to be 4.34 and 3.49 nm, respectively. Furthermore, circular dichroism spectra (CD), Fourier transforms infrared (FTIR), UV-vis, and three-dimensional fluorescence spectra results indicated the secondary structures of LYSO and BHb were partially destroyed by MNC with the α-helix percentage of LYZO-MNC increased (17.8-28.6%) while that of BHb-MNC was decreased (41.6-39.6%). UV-vis spectral results showed these binding interactions could cause conformational and some micro-environmental changes of LYSO and BHb. In accordance with the results of molecular docking, In LYZO-MNC system, MNC was mainly bound in the active site hinge region where Trp-62 and Trp-63 are located, and in MNC-BHb system, MNC was close to the subunit α 1 of BHb, molecular docking analysis supported the thermodynamic results well. The work contributes to clarify the mechanism of MNC with two proteins at molecular level.

  18. Shape Memory Alloy Cryogenic Transfer Coupling for Space Depot Docking Operations Project

    Data.gov (United States)

    National Aeronautics and Space Administration — In the proposed effort, we will demonstrate the feasibility of SMA-based actuation system by designing and fabricating a prototype sub-component of a locking...

  19. Research on docking mechanism for R & D satellite (ETS-X)

    Science.gov (United States)

    Shibuta, Shigeto; Morino, Yoshiki

    The National Space Development Agency of Japan (NASDA) has been executing research and development on unmanned rendezvous and docking (RVD) technology. This paper presents an interim report on design, dynamic simulation analysis and experimental results for several types of docking mechanisms (DM) that consisted of a probe and drogue type berthing mechanism, a low impact (low speed approaching) docking mechanism and umbilical connection devices. A selected docking mechanism will be installed on the ETS-X (Engineering Test Satellite type X) scheduled to be launched in 1997 for the first on-orbit RVD engineering test in Japan.

  20. 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

    2017-07-01

    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 (Ptail docking using either clippers or cautery results in neuroma formation, thus having the potential to affect long-term pig welfare.

  1. DOCK/PIERR: web server for structure prediction of protein-protein complexes.

    Science.gov (United States)

    Viswanath, Shruthi; Ravikant, D V S; Elber, Ron

    2014-01-01

    In protein docking we aim to find the structure of the complex formed when two proteins interact. Protein-protein interactions are crucial for cell function. Here we discuss the usage of DOCK/PIERR. In DOCK/PIERR, a uniformly discrete sampling of orientations of one protein with respect to the other, are scored, followed by clustering, refinement, and reranking of structures. The novelty of this method lies in the scoring functions used. These are obtained by examining hundreds of millions of correctly and incorrectly docked structures, using an algorithm based on mathematical programming, with provable convergence properties.

  2. Combining self- and cross-docking as benchmark tools: the performance of DockBench in the D3R Grand Challenge 2

    Science.gov (United States)

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

    2017-08-01

    Molecular docking is a powerful tool in the field of computer-aided molecular design. In particular, it is the technique of choice for the prediction of a ligand pose within its target binding site. A multitude of docking methods is available nowadays, whose performance may vary depending on the data set. Therefore, some non-trivial choices should be made before starting a docking simulation. In the same framework, the selection of the target structure to use could be challenging, since the number of available experimental structures is increasing. Both issues have been explored within this work. The pose prediction of a pool of 36 compounds provided by D3R Grand Challenge 2 organizers was preceded by a pipeline to choose the best protein/docking-method couple for each blind ligand. An integrated benchmark approach including ligand shape comparison and cross-docking evaluations was implemented inside our DockBench software. The results are encouraging and show that bringing attention to the choice of the docking simulation fundamental components improves the results of the binding mode predictions.

  3. 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.

  4. 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.

  5. 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.

  6. Laser space rendevous and docking trade-off

    Science.gov (United States)

    1974-01-01

    A spaceborne LADAR sensor, which will meet the requirements for rendezvous and docking with a cooperative object in synchronous orbit is presented. The sensor is being configured around a pulsed CO2 laser which can be constructed and deployed using technology which presently exists or is being developed, and which appears to lend itself very well to the envisioned family of space missions. In order to determine the applicability of the type of sensor being considered, the performance of a family of candidate sensors is being traded off as a function of size, weight, and power consumption. The maximum ranges being considered are 50, 100, 200, and 300 nautical miles.

  7. BENTUK KERJASAMA PUBLIC-PRIVATE PEMBANGUNAN GRAVING DOCK DAN MANAJEMEN GALANGAN KAPAL DENGAN METODE ANALYTICAL HIERARCHI PROCESS (AHP

    Directory of Open Access Journals (Sweden)

    Hartono Hartono

    2012-08-01

    Full Text Available In paper Development of port infrastructure in Indonesia is now no longer the responsibility of centralgovernment, along with limited funds and the government's insistence seaport infrastructure needs. Toaccelerate economic growth, the government issued Government Regulation as a legal umbrella. The purpose ofthis study was to examine public-private partnership opportunities in the construction of graving dock andshipyard management. Targets do is review, the criteria are prioritized cooperation and cooperationpriorities.This study used qualitative and quantitative approach, a descriptive qualitative approach throughinterviews used to assess the normative aspect. The quantitative approach used to assess the priority criteriaforms of cooperation and public-private partnership in development graving dock and shipyard management byusing the Analytical Hierarchy Process (AHP. Based on the AHP analysis can be concluded that the expertsdisagree about the priority criteria of cooperation, where the majority of them choose the duration as the maincriterion. As for the analysis of priorities of the cooperation of all experts choose Built-Operate-Transfer (BOT,which is deemed suitable for long-term investment of up to 30 years. BOT puts private partners to more freely tofinance, construct, operate, anticipated rate of return on capital (rate of return and the risks of commercial andregulatory aspects

  8. Milk β-casein as a vehicle for delivery of bis(indolyl)methane: Spectroscopy and molecular docking studies

    Science.gov (United States)

    Dezhampanah, Hamid; Esmaili, Masoomeh; Khorshidi, Alireza

    2017-05-01

    The interaction of bis(indolyl)methane with bovine milk β-casein was investigated using spectroscopy and molecular docking studies at different temperatures (25-37 °C). The circular dichroism and Fourier transform infrared spectroscopic data demonstrated that β-casein interacts with BIM molecule mainly via both the hydrophobic and hydrophilic interactions with a minor change in the secondary structure of β-casein. The fluorescence quenching measurements revealed that the presence of a single binding site on β-casein for BIM with the binding constant value of ∼104 M-1. The negative values of entropy and enthalpy changes confirm the predominate role of hydrogen binding and van der Waals interactions in the binding process. Fӧrster energy transfer measurement suggested that the distance between bound BIM and Trp residue is higher than the respective critical distance. Hence, the static quenching is more likely responsible for the fluorescence quenching rather than the mechanism of non-radiative. Docking study showed that BIM molecule forms three hydrogen bonds and several van der Waals contacts with β-casein.

  9. 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.

  10. Transfer Pricing

    DEFF Research Database (Denmark)

    Rohde, Carsten; Rossing, Christian Plesner

    trade internally as the units have to decide what prices should be paid for such inter-unit transfers. One important challenge is to uncover the consequences that different transfer prices have on the willingness in the organizational units to coordinate activities and trade internally. At the same time...

  11. Docking-based classification models for exploratory toxicology ...

    Science.gov (United States)

    Background: Exploratory toxicology is a new emerging research area whose ultimate mission is that of protecting human health and environment from risks posed by chemicals. In this regard, the ethical and practical limitation of animal testing has encouraged the promotion of computational methods for the fast screening of huge collections of chemicals available on the market. Results: We derived 24 reliable docking-based classification models able to predict the estrogenic potential of a large collection of chemicals having high quality experimental data, kindly provided by the U.S. Environmental Protection Agency (EPA). The predictive power of our docking-based models was supported by values of AUC, EF1% (EFmax = 7.1), -LR (at SE = 0.75) and +LR (at SE = 0.25) ranging from 0.63 to 0.72, from 2.5 to 6.2, from 0.35 to 0.67 and from 2.05 to 9.84, respectively. In addition, external predictions were successfully made on some representative known estrogenic chemicals. Conclusion: We show how structure-based methods, widely applied to drug discovery programs, can be adapted to meet the conditions of the regulatory context. Importantly, these methods enable one to employ the physicochemical information contained in the X-ray solved biological target and to screen structurally-unrelated chemicals. Shows how structure-based methods, widely applied to drug discovery programs, can be adapted to meet the conditions of the regulatory context. Evaluation of 24 reliable dockin

  12. A "Dock and Lock" Approach to Preparation of Targeted Liposomes.

    Science.gov (United States)

    Backer, Marina V; Backer, Joseph M

    2017-01-01

    We developed a strategy for covalent coupling of targeting proteins to liposomes decorated with a standard adapter protein. This strategy is based on "dock and lock" interactions between two mutated fragments of human RNase I, a 1-15 aa fragment with the R4C amino acid substitution (Cys-tag), and a 21-127-aa fragment with the V118C substitution, (Ad-C). Upon binding to each other, Cys-tag and Ad-C spontaneously form a disulfide bond between the complementary 4C and 118C residues. Therefore, any targeting protein expressed with Cys-tag can be easily coupled to liposomes decorated with Ad-C. Here we describe the preparation of Ad-liposomes followed by coupling them to two Cys-tagged targeted proteins, human vascular endothelial growth factor expressed with N-terminal Cys-tag and a 254-aa long N-terminal fragment of anthrax lethal factor carrying C-terminal Cys-tag. Both proteins retain functional activity after coupling to Ad-C-decorated drug-loaded liposomes. We expect that our "dock and lock" strategy will open new opportunities for development of targeted therapeutic liposomes for research and clinical use.

  13. Contact dynamics testing of automated three-point docking mechanism

    Science.gov (United States)

    Rourke, Kenneth H.

    An evaluation of an OMV docking mechanism, based on an adaptation of the Shuttle Flight Support System Pallet Berthing Mechanism was completed. The mechanism uses automatically actuated motorized latches to engage towel bars on the target satellite. LED sensors establish the towel bar position within the capture envelope and the latch capture commands are issued. Then, locking pawls engage the bar, locking and pre-loading the mechanism. Two series of tests were conducted to test nominal and failure mode captures and to evaluate design parameters such as LED sensor locations, automatic closure algorithms, latch closure velocity, position/velocity entry envelopes, and closure method. The first test series involved single latch testing on the Flat Floor Facility, the 6 DOF Facility, and an analytic simulation model. The intent was to compare results in order to validate the various facilities. Reasonably good agreement was achieved. The second test series repeated the single latch testing on the refurbished 6 DOF Facility to validate the facility modifications. The individual latches were tested under free-drift conditions for functionality and performance. Next, the three-latch configuration underwent parametric testing. Test results validated the improved fidelity of the 6 DOF Facility and verified successful docking at the required entry velocity. The tests determined the 'best' design parameter definitions and concluded that the locking pawls should not lock until all three latches completely close.

  14. Engineering Evaluation of International Low Impact Docking System Latch Hooks

    Science.gov (United States)

    Martinez, J.; Patin, R.; Figert, J.

    2013-01-01

    The international Low Impact Docking System (iLIDS) provides a structural arrangement that allows for visiting vehicles to dock with the International Space Station (ISS) (Fig 1). The iLIDS docking units are mechanically joined together by a series of active and passive latch hooks. In order to preserve docking capability at the existing Russian docking interfaces, the iLIDS latch hooks are required to conform to the existing Russian design. The latch hooks are classified as being fail-safe. Since the latch hooks are fail-safe, the hooks are not fracture critical and a fatigue based service life assessment will satisfy the structural integrity requirements. Constant amplitude fatigue testing to failure on four sets of active/passive iLIDS latch hooks was performed at load magnitudes of 10, 11, and 12 kips. Failure analysis of the hook fatigue failures identified multi-site fatigue initiation that was effectively centered about the hook mid-plane (consistent with the 3D model results). The fatigue crack initiation distribution implies that the fatigue damage accumulation effectively results in a very low aspect ratio surface crack (which can be simulated as thru-thickness crack). Fatigue damage progression resulted in numerous close proximity fatigue crack initiation sites. It was not possible to determine if fatigue crack coalescence occurs during cyclic loading or as result of the fast fracture response. The presence of multiple fatigue crack initiation sites on different planes will result in the formation of ratchet marks as the cracks coalesce. Once the stable fatigue crack becomes unstable and the fast fracture advances across the remaining ligament and the plane stress condition at a free-surface will result in failure along a 45 deg. shear plane (slant fracture) and the resulting inclined edge is called a shear lip. The hook thickness on the plane of fatigue crack initiation is 0.787". The distance between the shear lips on this plane was on the order of 0

  15. jMetalCpp: optimizing molecular docking problems with a C++ metaheuristic framework.

    Science.gov (United States)

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

    2014-02-01

    Molecular docking is a method for structure-based drug design and structural molecular biology, which attempts to predict the position and orientation of a small molecule (ligand) in relation to a protein (receptor) to produce a stable complex with a minimum binding energy. One of the most widely used software packages for this purpose is AutoDock, which incorporates three metaheuristic techniques. We propose the integration of AutoDock with jMetalCpp, an optimization framework, thereby providing both single- and multi-objective algorithms that can be used to effectively solve docking problems. The resulting combination of AutoDock + jMetalCpp allows users of the former to easily use the metaheuristics provided by the latter. In this way, biologists have at their disposal a richer set of optimization techniques than those already provided in AutoDock. Moreover, designers of metaheuristic techniques can use molecular docking for case studies, which can lead to more efficient algorithms oriented to solving the target problems.  jMetalCpp software adapted to AutoDock is freely available as a C++ source code at http://khaos.uma.es/AutodockjMetal/.

  16. 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

  17. Astronaut Donald Slayton checks out Docking Module back-up flight article

    Science.gov (United States)

    1974-01-01

    Astronaut Donald K. Slayton helps check out the Docking Module (DM) back-up flight article during Apollo Soyuz Test Project (ASTP) preflight preparations at JSC. Slayton, docking module pilot of the American ASTP crew, participates in a DM thermo-vacuum test walk through 'dry run' in Chamber B, Space Environment Simulation Laboratory, bldg 32, at JSC.

  18. 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 .

  19. DOCK8 deficiency impairs CD8 T cell survival and function in humans and mice

    Science.gov (United States)

    Randall, Katrina L.; Chan, Stephanie S.-Y.; Ma, Cindy S.; Fung, Ivan; Mei, Yan; Yabas, Mehmet; Tan, Andy; Arkwright, Peter D.; Al Suwairi, Wafaa; Lugo Reyes, Saul Oswaldo; Yamazaki-Nakashimada, Marco A.; de la Luz Garcia-Cruz, Maria; Smart, Joanne M.; Picard, Capucine; Okada, Satoshi; Jouanguy, Emmanuelle; Casanova, Jean-Laurent; Lambe, Teresa; Cornall, Richard J.; Russell, Sarah; Oliaro, Jane; Tangye, Stuart G.; Bertram, Edward M.

    2011-01-01

    In humans, DOCK8 immunodeficiency syndrome is characterized by severe cutaneous viral infections. Thus, CD8 T cell function may be compromised in the absence of DOCK8. In this study, by analyzing mutant mice and humans, we demonstrate a critical, intrinsic role for DOCK8 in peripheral CD8 T cell survival and function. DOCK8 mutation selectively diminished the abundance of circulating naive CD8 T cells in both species, and in DOCK8-deficient humans, most CD8 T cells displayed an exhausted CD45RA+CCR7− phenotype. Analyses in mice revealed the CD8 T cell abnormalities to be cell autonomous and primarily postthymic. DOCK8 mutant naive CD8 T cells had a shorter lifespan and, upon encounter with antigen on dendritic cells, exhibited poor LFA-1 synaptic polarization and a delay in the first cell division. Although DOCK8 mutant T cells underwent near-normal primary clonal expansion after primary infection with recombinant influenza virus in vivo, they showed greatly reduced memory cell persistence and recall. These findings highlight a key role for DOCK8 in the survival and function of human and mouse CD8 T cells. PMID:22006977

  20. "Flexible Ligand Docking Studies of Matrix Metalloproteinase Inhibitors Using Lamarckian Genetic Algorithm "

    Directory of Open Access Journals (Sweden)

    lOrkideh Ghorban Dadrass

    2004-06-01

    Full Text Available As important therapeutic drug targets, matrix metalloproteinases (MMPs have recently attracted great interest in the search for potent and selective inhibitors using computer-aided molecular modelling and docking techniques. Availability of more than 60 X-ray crystal structures or NMR solution structures related to MMPs in Protein Data Bank (PDB of which more than half of them are in complex with various MMP inhibitors (MMPIs, provides a great opportunity for docking studies. In this study AutoDock 3.0.5 along with its LGA algorithm were used for automated flexible ligand docking of 32 MMPI-MMP complexes and docking accuracy and reliability of the estimated inhibition constants were evaluated. Twenty-six out of 32 docks had RMSD less than 3.0 Å which is considered as well-docked, however, for the most of the cases (15 out of 27, predicted pKi values were considerably overestimated in comparison to experimental values. To improve pKi prediction regarding MMPI-MMP complexes, inclusion of at least one such a complex in calibration of empirical free energy function in the next release of AutoDock is highly recommended.

  1. A Multi-Sensory Autonomous Docking Approach for a Self-Reconfigurable Robot without Mechanical Guidance

    Directory of Open Access Journals (Sweden)

    Yanhe Zhu

    2014-09-01

    Full Text Available The most important feature of a Self-Reconfigurable Robot (SRR is that it is reconfigurable and self-repairing. At the centre of these capabilities is autonomous docking. One difficulty for docking is the alignment between two robots. Current strategies overcome this by integrating a mechanical guiding device within the connecting mechanism. This increases the robustness of docking but compromises the flexibility of reconfiguration. In this paper, we present a new autonomous docking strategy that can overcome the drawbacks of current approaches. The new strategy uses a novel hook-type connecting mechanism and multi-sensory guidance. The hook-type connecting mechanism is strong and rigid for reliable physical connection between the modules. The multi-sensory docking strategy, which includes visual-sensor-guided rough positioning, Hall-sensor-guided fine positioning, and the locking between moving and target modules, guarantees robust docking without sacrificing reconfigurability. The proposed strategy is verified by docking between a worm-shaped robot and one target module, and docking among three moving robots to form a T-shaped configuration. The experimental results showed that the strategy is very effective.

  2. 48 CFR 47.303-12 - Ex dock, pier, or warehouse, port of importation.

    Science.gov (United States)

    2010-10-01

    ... warehouse, port of importation. 47.303-12 Section 47.303-12 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACT MANAGEMENT TRANSPORTATION Transportation in Supply Contracts 47.303-12 Ex dock, pier, or warehouse, port of importation. (a) Explanation of delivery term. Ex dock, pier, or warehouse...

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

    Indian Academy of Sciences (India)

    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 ...

  4. Comparative docking studies of CYP1b1 and its PCG-associated ...

    Indian Academy of Sciences (India)

    Molecular docking has been used to compare and contrast the binding modes of oestradiol with the wild-type and some disease-associated mutant forms of the human CYP1b1 protein. The receptor structures used for docking were derived from molecular dynamics simulations of homology-modelled structures. Earlier ...

  5. Quantum-Mechanics Methodologies in Drug Discovery: Applications of Docking and Scoring in Lead Optimization.

    Science.gov (United States)

    Crespo, Alejandro; Rodriguez-Granillo, Agustina; Lim, Victoria T

    2017-01-01

    The development and application of quantum mechanics (QM) methodologies in computer- aided drug design have flourished in the last 10 years. Despite the natural advantage of QM methods to predict binding affinities with a higher level of theory than those methods based on molecular mechanics (MM), there are only a few examples where diverse sets of protein-ligand targets have been evaluated simultaneously. In this work, we review recent advances in QM docking and scoring for those cases in which a systematic analysis has been performed. In addition, we introduce and validate a simplified QM/MM expression to compute protein-ligand binding energies. Overall, QMbased scoring functions are generally better to predict ligand affinities than those based on classical mechanics. However, the agreement between experimental activities and calculated binding energies is highly dependent on the specific chemical series considered. The advantage of more accurate QM methods is evident in cases where charge transfer and polarization effects are important, for example when metals are involved in the binding process or when dispersion forces play a significant role as in the case of hydrophobic or stacking interactions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Docking optimization, variance and promiscuity for large-scale drug-like chemical space using high performance computing architectures.

    Science.gov (United States)

    Trager, Richard E; Giblock, Paul; Soltani, Sherwin; Upadhyay, Amit A; Rekapalli, Bhanu; Peterson, Yuri K

    2016-10-01

    There is a continuing need to hasten and improve protein-ligand docking to facilitate the next generation of drug discovery. As the drug-like chemical space reaches into the billions of molecules, increasingly powerful computer systems are required to probe, as well as tackle, the software engineering challenges needed to adapt existing docking programs to use next-generation massively parallel processing systems. We demonstrate docking setup using the wrapper code approach to optimize the DOCK program for large-scale computation as well as docking analysis using variance and promiscuity as examples. Wrappers provide faster docking speeds when compared with the naive multi-threading system MPI-DOCK, making future endeavors in large-scale docking more feasible; in addition, eliminating highly variant or promiscuous compounds will make databases more useful. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. DockBench: An Integrated Informatic Platform Bridging the Gap between the Robust Validation of Docking Protocols and Virtual Screening Simulations.

    Science.gov (United States)

    Cuzzolin, Alberto; Sturlese, Mattia; Malvacio, Ivana; Ciancetta, Antonella; Moro, Stefano

    2015-05-29

    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.

  8. 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.

  9. Ensemble-based docking: From hit discovery to metabolism and toxicity predictions.

    Science.gov (United States)

    Evangelista, Wilfredo; Weir, Rebecca L; Ellingson, Sally R; Harris, Jason B; Kapoor, Karan; Smith, Jeremy C; Baudry, Jerome

    2016-10-15

    This paper describes and illustrates the use of ensemble-based docking, i.e., using a collection of protein structures in docking calculations for hit discovery, the exploration of biochemical pathways and toxicity prediction of drug candidates. We describe the computational engineering work necessary to enable large ensemble docking campaigns on supercomputers. We show examples where ensemble-based docking has significantly increased the number and the diversity of validated drug candidates. Finally, we illustrate how ensemble-based docking can be extended beyond hit discovery and toward providing a structural basis for the prediction of metabolism and off-target binding relevant to pre-clinical and clinical trials. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. A novel approach for assesing macromolecular complexes combining soft-docking calculations with NMR data

    Science.gov (United States)

    Morelli, Xavier J.; Palma, P. Nuno; Guerlesquin, Françoise; Rigby, Alan C.

    2001-01-01

    We present a novel and efficient approach for assessing protein–protein complex formation, which combines ab initio docking calculations performed with the protein docking algorithm BiGGER and chemical shift perturbation data collected with heteronuclear single quantum coherence (HSQC) or TROSY nuclear magnetic resonance (NMR) spectroscopy. This method, termed "restrained soft-docking," is validated for several known protein complexes. These data demonstrate that restrained soft-docking extends the size limitations of NMR spectroscopy and provides an alternative method for investigating macromolecular protein complexes that requires less experimental time, effort, and resources. The potential utility of this novel NMR and simulated docking approach in current structural genomic initiatives is discussed. PMID:11567104

  11. 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.

  12. 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.

  13. Thermal transfer structures coupling electronics card(s) to coolant-cooled structure(s)

    Science.gov (United States)

    David, Milnes P; Graybill, David P; Iyengar, Madhusudan K; Kamath, Vinod; Kochuparambil, Bejoy J; Parida, Pritish R; Schmidt, Roger R

    2014-12-16

    Cooling apparatuses and coolant-cooled electronic systems are provided which include thermal transfer structures configured to engage with a spring force one or more electronics cards with docking of the electronics card(s) within a respective socket(s) of the electronic system. A thermal transfer structure of the cooling apparatus includes a thermal spreader having a first thermal conduction surface, and a thermally conductive spring assembly coupled to the conduction surface of the thermal spreader and positioned and configured to reside between and physically couple a first surface of an electronics card to the first surface of the thermal spreader with docking of the electronics card within a socket of the electronic system. The thermal transfer structure is, in one embodiment, metallurgically bonded to a coolant-cooled structure and facilitates transfer of heat from the electronics card to coolant flowing through the coolant-cooled structure.

  14. ANALISA TEKNIS DAN EKONOMIS SISTEM PERBAIKAN DAUN PROPELLER YANG PATAH PADA KM. MANDIRI DUA TANPA DOCKING

    Directory of Open Access Journals (Sweden)

    Parlindungan Manik

    2012-03-01

    Full Text Available At a sailing in a territorial to sea or river, ship propeller frequently collide object or foreign object which float, causing damage at propeller, throw in the form of curving, crack or broken at propeller blade. When this damage do not improve immediately; repaired will generate harm effect to ship construction or parts of machinery. Therefore ship should be immediately to repair (emergency docking to improve the propeller. But is not easy to get docking space to repair because docking space schedule is very strike, existing graving dock in country. So that ship have to kick one's heels to be able to docking space, which meaning of big loss of time and also expense. The air of this research technical analysis possibility implementation to propeller repairf by floating repair system in territorial water closest with damage location of propeller and compare efficiency economic value and time if repair of propeller done in graving dock or executed by floating repair in graving dock. In this research, repair propeller without docking can be executed by arranging ship trim by arranging ballast tank to be reached space which last for working. Hereinafter worked repair of blade propeller thickly , pitch, aerofoil, wide of blade, obtained mains material type from source which have been collected by either from Owner Surveyor, picture - technique picture and also blade propeller which still goodness. Result of analysis indicate that technically repair of propeller which broken can be executed without docking and economically will be more be efficient up to 700%,in comparison with executed in Graving Dock, and will be more be efficient up to 300% when compared with executed in floating repair system

  15. Modification of S-Adenosyl-l-Homocysteine as Inhibitor of Nonstructural Protein 5 Methyltransferase Dengue Virus Through Molecular Docking and Molecular Dynamics Simulation

    Science.gov (United States)

    Tambunan, Usman Sumo Friend; Nasution, Mochammad Arfin Fardiansyah; Azhima, Fauziah; Parikesit, Arli Aditya; Toepak, Erwin Prasetya; Idrus, Syarifuddin; Kerami, Djati

    2017-01-01

    Dengue fever is still a major threat worldwide, approximately threatening two-fifths of the world’s population in tropical and subtropical countries. Nonstructural protein 5 (NS5) methyltransferase enzyme plays a vital role in the process of messenger RNA capping of dengue by transferring methyl groups from S-adenosyl-l-methionine to N7 atom of the guanine bases of RNA and the RNA ribose group of 2′OH, resulting in S-adenosyl-l-homocysteine (SAH). The modification of SAH compound was screened using molecular docking and molecular dynamics simulation, along with computational ADME-Tox (absorption, distribution, metabolism, excretion, and toxicity) test. The 2 simulations were performed using Molecular Operating Environment (MOE) 2008.10 software, whereas the ADME-Tox test was performed using various software. The modification of SAH compound was done using several functional groups that possess different polarities and properties, resulting in 3460 ligands to be docked. After conducting docking simulation, we earned 3 best ligands (SAH-M331, SAH-M2696, and SAH-M1356) based on ΔGbinding and molecular interactions, which show better results than the standard ligands. Moreover, the results of molecular dynamics simulation show that the best ligands are still able to maintain the active site residue interaction with the binding site until the end of the simulation. After a series of molecular docking and molecular dynamics simulation were performed, we concluded that SAH-M1356 ligand is the most potential SAH-based compound to inhibit NS5 methyltransferase enzyme for treating dengue fever. PMID:28469408

  16. Modification of S-Adenosyl-l-Homocysteine as Inhibitor of Nonstructural Protein 5 Methyltransferase Dengue Virus Through Molecular Docking and Molecular Dynamics Simulation.

    Science.gov (United States)

    Tambunan, Usman Sumo Friend; Nasution, Mochammad Arfin Fardiansyah; Azhima, Fauziah; Parikesit, Arli Aditya; Toepak, Erwin Prasetya; Idrus, Syarifuddin; Kerami, Djati

    2017-01-01

    Dengue fever is still a major threat worldwide, approximately threatening two-fifths of the world's population in tropical and subtropical countries. Nonstructural protein 5 (NS5) methyltransferase enzyme plays a vital role in the process of messenger RNA capping of dengue by transferring methyl groups from S-adenosyl-l-methionine to N7 atom of the guanine bases of RNA and the RNA ribose group of 2'OH, resulting in S-adenosyl-l-homocysteine (SAH). The modification of SAH compound was screened using molecular docking and molecular dynamics simulation, along with computational ADME-Tox (absorption, distribution, metabolism, excretion, and toxicity) test. The 2 simulations were performed using Molecular Operating Environment (MOE) 2008.10 software, whereas the ADME-Tox test was performed using various software. The modification of SAH compound was done using several functional groups that possess different polarities and properties, resulting in 3460 ligands to be docked. After conducting docking simulation, we earned 3 best ligands (SAH-M331, SAH-M2696, and SAH-M1356) based on ΔGbinding and molecular interactions, which show better results than the standard ligands. Moreover, the results of molecular dynamics simulation show that the best ligands are still able to maintain the active site residue interaction with the binding site until the end of the simulation. After a series of molecular docking and molecular dynamics simulation were performed, we concluded that SAH-M1356 ligand is the most potential SAH-based compound to inhibit NS5 methyltransferase enzyme for treating dengue fever.

  17. Modification of -Adenosyl--Homocysteine as Inhibitor of Nonstructural Protein 5 Methyltransferase Dengue Virus Through Molecular Docking and Molecular Dynamics Simulation

    Directory of Open Access Journals (Sweden)

    Usman Sumo Friend Tambunan

    2017-04-01

    Full Text Available Dengue fever is still a major threat worldwide, approximately threatening two-fifths of the world’s population in tropical and subtropical countries. Nonstructural protein 5 (NS5 methyltransferase enzyme plays a vital role in the process of messenger RNA capping of dengue by transferring methyl groups from S -adenosyl- l -methionine to N7 atom of the guanine bases of RNA and the RNA ribose group of 2′OH, resulting in S -adenosyl- l -homocysteine (SAH. The modification of SAH compound was screened using molecular docking and molecular dynamics simulation, along with computational ADME-Tox (absorption, distribution, metabolism, excretion, and toxicity test. The 2 simulations were performed using Molecular Operating Environment (MOE 2008.10 software, whereas the ADME-Tox test was performed using various software. The modification of SAH compound was done using several functional groups that possess different polarities and properties, resulting in 3460 ligands to be docked. After conducting docking simulation, we earned 3 best ligands (SAH-M331, SAH-M2696, and SAH-M1356 based on ΔG binding and molecular interactions, which show better results than the standard ligands. Moreover, the results of molecular dynamics simulation show that the best ligands are still able to maintain the active site residue interaction with the binding site until the end of the simulation. After a series of molecular docking and molecular dynamics simulation were performed, we concluded that SAH-M1356 ligand is the most potential SAH-based compound to inhibit NS5 methyltransferase enzyme for treating dengue fever.

  18. Station Transfers

    Data.gov (United States)

    Department of Homeland Security — ixed rail transit external system transfers for systems within the Continental United States, Alaska, Hawaii, the District of Columbia, and Puerto Rico. The modes of...

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

    DEFF Research Database (Denmark)

    Frank, Scott 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...

  20. 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

  1. Clarifying off-target effects for torcetrapib using network pharmacology and reverse docking approach

    Directory of Open Access Journals (Sweden)

    Fan Shengjun

    2012-12-01

    Full Text Available Abstract Background Torcetrapib, a cholesteryl ester transfer protein (CETP inhibitor which raises high-density lipoprotein (HDL cholesterol and reduces low-density lipoprotein (LDL cholesterol level, has been documented to increase mortality and cardiac events associated with adverse effects. However, it is still unclear the underlying mechanisms of the off-target effects of torcetrapib. Results In the present study, we developed a systems biology approach by combining a human reassembled signaling network with the publicly available microarray gene expression data to provide unique insights into the off-target adverse effects for torcetrapib. Cytoscape with three plugins including BisoGenet, NetworkAnalyzer and ClusterONE was utilized to establish a context-specific drug-gene interaction network. The DAVID functional annotation tool was applied for gene ontology (GO analysis, while pathway enrichment analysis was clustered by ToppFun. Furthermore, potential off-targets of torcetrapib were predicted by a reverse docking approach. In general, 10503 nodes were retrieved from the integrative signaling network and 47660 inter-connected relations were obtained from the BisoGenet plugin. In addition, 388 significantly up-regulated genes were detected by Significance Analysis of Microarray (SAM in adrenal carcinoma cells treated with torcetrapib. After constructing the human signaling network, the over-expressed microarray genes were mapped to illustrate the context-specific network. Subsequently, three conspicuous gene regulatory networks (GRNs modules were unearthed, which contributed to the off-target effects of torcetrapib. GO analysis reflected dramatically over-represented biological processes associated with torcetrapib including activation of cell death, apoptosis and regulation of RNA metabolic process. Enriched signaling pathways uncovered that IL-2 Receptor Beta Chain in T cell Activation, Platelet-Derived Growth Factor Receptor (PDGFR beta

  2. iLIDS Simulations and Videos for Docking TIM

    Science.gov (United States)

    Lewis, James L.

    2010-01-01

    The video shows various aspects of the International Low Impact Docking System, including team members, some production, configuration, mated androgynous iLIDS, SCS Lockdown system, thermal analysis, electrical engineering aspects, the iLIDS control box and emulator, radiation testing at BNL, component environmental testing, component vibration testing, 3G processor board delivery system, GTA vibe test, EMA testbed, hook and hook disassembly, flex shaftdrive assembly, GSE cradle MISSE-6 Columbus, MISSE 6 and 7 seal experiments, actuated full scale seal test rig, LIDS on Hubble, dynamics test prep, EDU 54 mass emulation and SCS, load ring characterization, 6DOF proof test, SCS at 6DOF, machining EEMS and inner ring assembly, APAS assembly, inner ring fitting, rotation stand assembly, EEMS mating, and EEMS proof of concept demonstration.

  3. Mortality among dock-yard workers in Genoa, Italy.

    Science.gov (United States)

    Puntoni, R; Russo, L; Zannini, D; Vercelli, M; Gambaro, R P; Valerio, F; Santi, L

    1977-01-01

    The causes of death among the dock-yard workers of Genoa from December 31, 1959 to January 1, 1970, have been investigated. These workers, mainly assigned to ship repair, refitting and construction, are exposed to several noxious substances, such as: asbestos, silica, paint solvents, welding smoke and volatile products of petroleum. Two different control groups were selected: the male population of Genoa and the staff of the San Martino Hospital in Genoa. Causes of death showing a significant increase were: gastric cancer (only in comparison with the hospital staff), cancer of colon excluding rectum, lung cancer, cancer of kidney, urinary bladder and other urinary organs, respiratory diseases, cirrhosis of the liver, cardiovascular diseases (only in comparison with the hospital staff).

  4. Space vehicle with customizable payload and docking station

    Energy Technology Data Exchange (ETDEWEB)

    Judd, Stephen; Dallmann, Nicholas; McCabe, Kevin; Seitz, Daniel

    2018-01-30

    A "black box" space vehicle solution may allow a payload developer to define the mission space and provide mission hardware within a predetermined volume and with predetermined connectivity. Components such as the power module, radios and boards, attitude determination and control system (ADCS), command and data handling (C&DH), etc. may all be provided as part of a "stock" (i.e., core) space vehicle. The payload provided by the payload developer may be plugged into the space vehicle payload section, tested, and launched without custom development of core space vehicle components by the payload developer. A docking station may facilitate convenient development and testing of the space vehicle while reducing handling thereof.

  5. Hydrogen bond docking site competition in methyl esters.

    Science.gov (United States)

    Zhao, Hailiang; Tang, Shanshan; Du, Lin

    2017-06-15

    The OH⋯O hydrogen bonds in the 2,2,2-trifluoroethanol (TFE)-methyl ester complexes in the gas phase have been investigated by FTIR spectroscopy and DFT calculations. Methyl formate (MF), methyl acetate (MA), and methyl trifluoroacetate (MTFA) were chosen as the hydrogen bond acceptors. A dominant inter-molecular hydrogen bond was formed between the OH group of TFE and different docking sites in the methyl esters (carbonyl oxygen or ester oxygen). The competition of the two docking sites decides the structure and spectral properties of the complexes. On the basis of the observed red shifts of the OH-stretching transition with respect to the TFE monomer, the order of the hydrogen bond strength can be sorted as TFE-MA (119cm-1)>TFE-MF (93cm-1)>TFE-MTFA (44cm-1). Combining the experimental infrared spectra with the DFT calculations, the Gibbs free energies of formation were determined to be 1.5, 4.5 and 8.6kJmol-1 for TFE-MA, TFE-MF and TFE-MTFA, respectively. The hydrogen bonding in the MTFA complex is much weaker than those of the TFE-MA and TFE-MF complexes due to the effect of the CF3 substitution on MTFA, while the replacement of an H atom with a CH3 group in methyl ester only slightly increases the hydrogen bond strength. Topological analysis and localized molecular orbital energy decomposition analysis was also applied to compare the interactions in the complexes. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Hydrogen bond docking site competition in methyl esters

    Science.gov (United States)

    Zhao, Hailiang; Tang, Shanshan; Du, Lin

    2017-06-01

    The Osbnd H ⋯ O hydrogen bonds in the 2,2,2-trifluoroethanol (TFE)-methyl ester complexes in the gas phase have been investigated by FTIR spectroscopy and DFT calculations. Methyl formate (MF), methyl acetate (MA), and methyl trifluoroacetate (MTFA) were chosen as the hydrogen bond acceptors. A dominant inter-molecular hydrogen bond was formed between the OH group of TFE and different docking sites in the methyl esters (carbonyl oxygen or ester oxygen). The competition of the two docking sites decides the structure and spectral properties of the complexes. On the basis of the observed red shifts of the OH-stretching transition with respect to the TFE monomer, the order of the hydrogen bond strength can be sorted as TFE-MA (119 cm- 1) > TFE-MF (93 cm- 1) > TFE-MTFA (44 cm- 1). Combining the experimental infrared spectra with the DFT calculations, the Gibbs free energies of formation were determined to be 1.5, 4.5 and 8.6 kJ mol- 1 for TFE-MA, TFE-MF and TFE-MTFA, respectively. The hydrogen bonding in the MTFA complex is much weaker than those of the TFE-MA and TFE-MF complexes due to the effect of the CF3 substitution on MTFA, while the replacement of an H atom with a CH3 group in methyl ester only slightly increases the hydrogen bond strength. Topological analysis and localized molecular orbital energy decomposition analysis was also applied to compare the interactions in the complexes.

  7. Solving a molecular docking problem by the modified PSO method

    Directory of Open Access Journals (Sweden)

    A. P. Karpenko

    2014-01-01

    Full Text Available The paper presents an canonical method of the swarm particles in two modifications to raise this method efficiency in solving multi-extreme problems of high dimension optimization. The essence of PSO-M1 modification is to form two new points to attract swarm particles (along with the points which are responsible for inertial, cognitive, and social components of canonical method. These new points represent the best points of sets of particles-neighbours of a given point. The modification aims to diversify search. All free parameters of the PSO-M1 method (as well as an canonical method are static. In contrast, one of such parameters of PSO-M2 modification is dynamic. So this modification represents an example of a self-adaptive method of optimization. The modification aims to intensify search. A computing experiment to study the method efficiency and its abovementioned modifications at solving the test problems of optimization showed advantages of offered modifications in comparison with canonical method, revealed a superiority of PSO-M2 modification both over canonical method, and over PSO-M1 modification. Using the PSO-M2 method allows us to solve the 28-dimensional molecular docking problem of HIV1 protease and darunaviry 3U7S as the molecules of receptor and a ligand, respectively. Results of computing experiment have shown that the PSO-M2 method successfully finds the position of ligand close to native and can be recommended for solving the molecular docking problems as an alternative to genetic algorithm.

  8. Fast and accurate grid representations for atom-based docking with partner flexibility.

    Science.gov (United States)

    de Vries, Sjoerd J; Zacharias, Martin

    2017-06-30

    Macromolecular docking methods can broadly be divided into geometric and atom-based methods. Geometric methods use fast algorithms that operate on simplified, grid-like molecular representations, while atom-based methods are more realistic and flexible, but far less efficient. Here, a hybrid approach of grid-based and atom-based docking is presented, combining precalculated grid potentials with neighbor lists for fast and accurate calculation of atom-based intermolecular energies and forces. The grid representation is compatible with simultaneous multibody docking and can tolerate considerable protein flexibility. When implemented in our docking method ATTRACT, grid-based docking was found to be ∼35x faster. With the OPLSX forcefield instead of the ATTRACT coarse-grained forcefield, the average speed improvement was >100x. Grid-based representations may allow atom-based docking methods to explore large conformational spaces with many degrees of freedom, such as multiple macromolecules including flexibility. This increases the domain of biological problems to which docking methods can be applied. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  9. 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.

  10. Molecular Docking Improvement: Coefficient Adaptive Genetic Algorithms for Multiple Scoring Functions

    Directory of Open Access Journals (Sweden)

    Zhengfu Li

    2014-03-01

    Full Text Available In this paper, a coefficient adaptive scoring method of molecular docking is presented to improve the docking accuracy with multiple available scoring functions. Based on force-field scoring function, we considered hydrophobic and deformation as well in the proposed method, Instead of simple combination with fixed weights, coefficients of each factor are adaptive in searching procedure. In order to improve the docking accuracy and stability, knowledge-based scoring function is used as another scoring factor. Genetic algorithm with the multi-population evolution and entropy-based searching technique with narrowing down space is used to solve the optimization model for molecular docking. To evaluate the method, we carried out a numerical experiment with 134 protein- ligand complexes of the publicly available GOLD test set. The results validated that it improved the docking accuracy over the individual force-field scoring. In addition, analyses were given to show the disadvantage of individual scoring model. Through the comparison with other popular docking software, the proposed method showed higher accuracy. Among more than 77% of the complexes, the docked results were within 1.0 Å according to Root- Mean-Square Deviation (RMSD of the X-ray structure. The average computing time obtained here is 563.9 s.

  11. 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.

  12. DNA and HSA interaction of Vanadium (IV), Copper (II), and Zinc (II) complexes derived from an asymmetric bidentate Schiff-base ligand: multi spectroscopic, viscosity measurements, molecular docking, and ONIOM studies.

    Science.gov (United States)

    Dehkhodaei, Monireh; Sahihi, Mehdi; Amiri Rudbari, Hadi; Momenbeik, Fariborz

    2018-03-01

    The interaction of three complexes [Zn(II), Cu(II), and V(IV)] derived from an asymmetric bidentate Schiff-base ligand with DNA and HSA was studied using fluorescence quenching, UV-Vis spectroscopy, viscosity measurements, and computational methods [molecular docking and our Own N-layered Integrated molecular Orbital and molecular Mechanics (ONIOM)]. The obtained results revealed that the DNA and HSA affinities for binding of the synthesized compounds follow as V(IV) > Zn(II) > Cu(II) and Zn(II) > V(IV) > Cu(II), respectively. The distance between these compounds and HSA was obtained based on the Förster's theory of non-radiative energy transfer. Furthermore, computational molecular docking was carried out to investigate the DNA- and HSA-binding pose of the compounds. Molecular docking calculations showed that H-bond, hydrophobic, and π-cation interactions have dominant role in stability of the compound-HSA complexes. ONIOM method was utilized to investigate the HSA binding of the 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, indicating the strong interaction between the compounds with HSA and DNA. Viscosity measurements as well as computational docking data suggest that all metal complexes interact with DNA, presumably by groove-binding mechanism.

  13. An interaction-motif-based scoring function for protein-ligand docking

    Directory of Open Access Journals (Sweden)

    Xie Zhong-Ru

    2010-06-01

    Full Text Available Abstract Background A good scoring function is essential for molecular docking computations. In conventional scoring functions, energy terms modeling pairwise interactions are cumulatively summed, and the best docking solution is selected. Here, we propose to transform protein-ligand interactions into three-dimensional geometric networks, from which recurring network substructures, or network motifs, are selected and used to provide probability-ranked interaction templates with which to score docking solutions. Results A novel scoring function for protein-ligand docking, MotifScore, was developed. It is non-energy-based, and docking is, instead, scored by counting the occurrences of motifs of protein-ligand interaction networks constructed using structures of protein-ligand complexes. MotifScore has been tested on a benchmark set established by others to assess its ability to identify near-native complex conformations among a set of decoys. In this benchmark test, 84% of the highest-scored docking conformations had root-mean-square deviations (rmsds below 2.0 Å from the native conformation, which is comparable with the best of several energy-based docking scoring functions. Many of the top motifs, which comprise a multitude of chemical groups that interact simultaneously and make a highly significant contribution to MotifScore, capture recurrent interacting patterns beyond pairwise interactions. Conclusions While providing quite good docking scores, MotifScore is quite different from conventional energy-based functions. MotifScore thus represents a new, network-based approach for exploring problems associated with molecular docking.

  14. The Drosophila DOCK family protein sponge is involved in differentiation of R7 photoreceptor cells.

    Science.gov (United States)

    Eguchi, Koichi; Yoshioka, Yasuhide; Yoshida, Hideki; Morishita, Kazushige; Miyata, Seiji; Hiai, Hiroshi; Yamaguchi, Masamitsu

    2013-08-15

    The Drosophila sponge (spg)/CG31048 gene belongs to the dedicator of cytokinesis (DOCK) family genes that are conserved in a wide variety of species. DOCK family members are known as DOCK1-DOCK11 in mammals. Although DOCK1 and DOCK2 involve neurite elongation and immunocyte differentiation, respectively, the functions of other DOCK family members are not fully understood. Spg is a Drosophila homolog of mammalian DOCK3 and DOCK4. Specific knockdown of spg by the GMR-GAL4 driver in eye imaginal discs induced abnormal eye morphology in adults. To mark the photoreceptor cells in eye imaginal discs, we used a set of enhancer trap strains that express lacZ in various sets of photoreceptor cells. Immunostaining with anti-Spg antibodies and anti-lacZ antibodies revealed that Spg is localized mainly in R7 photoreceptor cells. Knockdown of spg by the GMR-GAL4 driver reduced signals of R7 photoreceptor cells, suggesting involvement of Spg in R7 cell differentiation. Furthermore, immunostaining with anti-dpERK antibodies showed the level of activated ERK signal was reduced extensively by knockdown of spg in eye discs, and both the defects in eye morphology and dpERK signals were rescued by over-expression of the Drosophila raf gene, a component of the ERK signaling pathway. Furthermore, the Duolink in situ Proximity Ligation Assay method detected interaction signals between Spg and Rap1 in and around the plasma membrane of the eye disc cells. Together, these results indicate Spg positively regulates the ERK pathway that is required for R7 photoreceptor cell differentiation and the regulation is mediated by interaction with Rap1 during development of the compound eye. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. 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.

  16. istar: a web platform for large-scale protein-ligand docking.

    Science.gov (United States)

    Li, Hongjian; Leung, Kwong-Sak; Ballester, Pedro J; Wong, Man-Hon

    2014-01-01

    Protein-ligand docking is a key computational method in the design of starting points for the drug discovery process. We are motivated by the desire to automate large-scale docking using our popular docking engine idock and thus have developed a publicly-accessible web platform called istar. Without tedious software installation, users can submit jobs using our website. Our istar website supports 1) filtering ligands by desired molecular properties and previewing the number of ligands to dock, 2) monitoring job progress in real time, and 3) visualizing ligand conformations and outputting free energy and ligand efficiency predicted by idock, binding affinity predicted by RF-Score, putative hydrogen bonds, and supplier information for easy purchase, three useful features commonly lacked on other online docking platforms like DOCK Blaster or iScreen. We have collected 17,224,424 ligands from the All Clean subset of the ZINC database, and revamped our docking engine idock to version 2.0, further improving docking speed and accuracy, and integrating RF-Score as an alternative rescoring function. To compare idock 2.0 with the state-of-the-art AutoDock Vina 1.1.2, we have carried out a rescoring benchmark and a redocking benchmark on the 2,897 and 343 protein-ligand complexes of PDBbind v2012 refined set and CSAR NRC HiQ Set 24Sept2010 respectively, and an execution time benchmark on 12 diverse proteins and 3,000 ligands of different molecular weight. Results show that, under various scenarios, idock achieves comparable success rates while outperforming AutoDock Vina in terms of docking speed by at least 8.69 times and at most 37.51 times. When evaluated on the PDBbind v2012 core set, our istar platform combining with RF-Score manages to reproduce Pearson's correlation coefficient and Spearman's correlation coefficient of as high as 0.855 and 0.859 respectively between the experimental binding affinity and the predicted binding affinity of the docked conformation. istar

  17. An Evolvement-based Genetic Algorithm for Computer-aided Molecular Docking

    Science.gov (United States)

    Ling, Kang; Xiaoyu, Zhao; Xi, Chen; Xicheng, Wang

    2010-05-01

    Species dynamics model is introduced into the genetic algorithm to reflect the true state of evolution. An adaptive evolution algorithm is developed. In the algorithm, an adaptive strategy is used to overcome the difficulty of confirming the crossover and mutation probabilities. Small population strategy and optimal strategy ensure the diversity of the populations. Numerical results show that introducing species dynamics model can improve the efficiency of the algorithm. Based on the genetic algorithm, a new molecular docking program is developed. Docking result indicates that the algorithm can effectively solve the molecular docking problem.

  18. 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.

  19. Predictive Power of Different Types of Experimental Restraints in Small Molecule Docking: A Review.

    Science.gov (United States)

    Fu, Darwin Y; Meiler, Jens

    2018-01-18

    Incorporating experimental restraints is a powerful method of increasing accuracy in computational protein small molecule docking simulations. Different algorithms integrate distinct forms of biochemical data during the docking and/or scoring stages. These so-called hybrid methods make use of receptor-based information such as nuclear magnetic resonance (NMR) restraints or small molecule-based information such as structure-activity relationships (SARs). A third class of methods directly interrogates contacts between the protein receptor and the small molecule. This work reviews the current state of using such restraints in docking simulations, evaluates their feasibility across broad systems, and identifies potential areas of algorithm development.

  20. 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

  1. TRANSFERENCE LOVE

    OpenAIRE

    Deneanu, Daniela

    2011-01-01

    It is the psychoanalysis’ merit to have discovered one of most common phenomenon that happens in almost all kind of human relations, and that is transference. Psychoanalytic framework did not produce it, but stimulate it. Transference love—one of the most powerful tool used by the analyst to get to understand a pacient’s pattern of falling in love—is an emotional relationship (a conglomeration of affection, tenderness, friendship, erotic and sexual feelings) developed by a pacient for his/her...

  2. Ligand-biased ensemble receptor docking (LigBEnD): a hybrid ligand/receptor structure-based approach

    Science.gov (United States)

    Lam, Polo C.-H.; Abagyan, Ruben; Totrov, Maxim

    2017-09-01

    Ligand docking to flexible protein molecules can be efficiently carried out through ensemble docking to multiple protein conformations, either from experimental X-ray structures or from in silico simulations. The success of ensemble docking often requires the careful selection of complementary protein conformations, through docking and scoring of known co-crystallized ligands. False positives, in which a ligand in a wrong pose achieves a better docking score than that of native pose, arise as additional protein conformations are added. In the current study, we developed a new ligand-biased ensemble receptor docking method and composite scoring function which combine the use of ligand-based atomic property field (APF) method with receptor structure-based docking. This method helps us to correctly dock 30 out of 36 ligands presented by the D3R docking challenge. For the six mis-docked ligands, the cognate receptor structures prove to be too different from the 40 available experimental Pocketome conformations used for docking and could be identified only by receptor sampling beyond experimentally explored conformational subspace.

  3. Multiple receptor conformation docking, dock pose clustering and 3D QSAR studies on human poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors.

    Science.gov (United States)

    Fatima, Sabiha; Jatavath, Mohan Babu; Bathini, Raju; Sivan, Sree Kanth; Manga, Vijjulatha

    2014-10-01

    Poly(ADP-ribose) polymerase-1 (PARP-1) functions as a DNA damage sensor and signaling molecule. It plays a vital role in the repair of DNA strand breaks induced by radiation and chemotherapeutic drugs; inhibitors of this enzyme have the potential to improve cancer chemotherapy or radiotherapy. Three-dimensional quantitative structure activity relationship (3D QSAR) models were developed using comparative molecular field analysis, comparative molecular similarity indices analysis and docking studies. A set of 88 molecules were docked into the active site of six X-ray crystal structures of poly(ADP-ribose)polymerase-1 (PARP-1), by a procedure called multiple receptor conformation docking (MRCD), in order to improve the 3D QSAR models through the analysis of binding conformations. The docked poses were clustered to obtain the best receptor binding conformation. These dock poses from clustering were used for 3D QSAR analysis. Based on MRCD and QSAR information, some key features have been identified that explain the observed variance in the activity. Two receptor-based QSAR models were generated; these models showed good internal and external statistical reliability that is evident from the [Formula: see text], [Formula: see text] and [Formula: see text]. The identified key features enabled us to design new PARP-1 inhibitors.

  4. Transfer Timing

    OpenAIRE

    2003-01-01

    sim present Simulation Presentation Interactive Media Element This IME is used in the Computer Communications and Networks class offered in the Graduate School of Operations and Information Sciences. This introductory computer networking course provides the theory and principles of networking and communications protocols. This IME is used to help students understand data transfer options. CS3502 Computer Communications and Networks

  5. Seamless Transfers

    Science.gov (United States)

    Patton, Carol

    2017-01-01

    In 2014, approximately 7.3 million undergraduate students (42 percent) were enrolled in community colleges in the US, the latest statistic offered by the Community College Research Center. At some schools, like Cleveland State University (OH), more transfer students graduated in 2014 with a bachelor's degree than students who entered four-year…

  6. Galaxy7TM: flexible GPCR-ligand docking by structure refinement.

    Science.gov (United States)

    Lee, Gyu Rie; Seok, Chaok

    2016-07-08

    G-protein-coupled receptors (GPCRs) play important physiological roles related to signal transduction and form a major group of drug targets. Prediction of GPCR-ligand complex structures has therefore important implications to drug discovery. With previously available servers, it was only possible to first predict GPCR structures by homology modeling and then perform ligand docking on the model structures. However, model structures generated without explicit consideration of specific ligands of interest can be inaccurate because GPCR structures can be affected by ligand binding. The Galaxy7TM server, freely accessible at http://galaxy.seoklab.org/7TM, improves an input GPCR structure by simultaneous ligand docking and flexible structure refinement using GALAXY methods. The server shows better performance in both ligand docking and GPCR structure refinement than commonly used programs AutoDock Vina and Rosetta MPrelax, respectively. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  7. 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. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. HexServer: an FFT-based protein docking server powered by graphics processors.

    Science.gov (United States)

    Macindoe, Gary; Mavridis, Lazaros; Venkatraman, Vishwesh; Devignes, Marie-Dominique; Ritchie, David W

    2010-07-01

    HexServer (http://hexserver.loria.fr/) is the first Fourier transform (FFT)-based protein docking server to be powered by graphics processors. Using two graphics processors simultaneously, a typical 6D docking run takes approximately 15 s, which is up to two orders of magnitude faster than conventional FFT-based docking approaches using comparable resolution and scoring functions. The server requires two protein structures in PDB format to be uploaded, and it produces a ranked list of up to 1000 docking predictions. Knowledge of one or both protein binding sites may be used to focus and shorten the calculation when such information is available. The first 20 predictions may be accessed individually, and a single file of all predicted orientations may be downloaded as a compressed multi-model PDB file. The server is publicly available and does not require any registration or identification by the user.

  9. Molecular Docking Studies of Flavonoids Derivatives on the Flavonoid 3- O-Glucosyltransferase.

    Science.gov (United States)

    Harsa, Alexandra M; Harsa, Teodora E; Diudea, Mircea V; Janezic, Dusanka

    2015-01-01

    A study of 30 flavonoid derivatives, taken from PubChem database and docked on flavonoid 3-O-glucosyltransferase 3HBF, next submitted to a QSAR study, performed within a hypermolecule frame, to model their LD50 values, is reported. The initial set of molecules was split into a training set and the test set (taken from the best scored molecules in the docking test); the predicted LD50 values, computed on similarity clusters, built up for each of the molecules of the test set, surpassed in accuracy the best model. The binding energies to 3HBF protein, provided by the docking step, are not related to the LD50 of these flavonoids, more protein targets are to be investigated in this respect. However, the docking step was useful in choosing the test set of molecules.

  10. dMM-PBSA : A New HADDOCK Scoring Function for Protein-Peptide Docking

    NARCIS (Netherlands)

    Spiliotopoulos, Dimitrios; Kastritis, Panagiotis L; Melquiond, Adrien S J; Bonvin, Alexandre M J J; Musco, Giovanna; Rocchia, Walter; Spitaleri, Andrea

    2016-01-01

    Molecular-docking programs coupled with suitable scoring functions are now established and very useful tools enabling computational chemists to rapidly screen large chemical databases and thereby to identify promising candidate compounds for further experimental processing. In a broader scenario,

  11. Fusion Competent Synaptic Vesicles Persist upon Active Zone Disruption and Loss of Vesicle Docking.

    Science.gov (United States)

    Wang, Shan Shan H; Held, Richard G; Wong, Man Yan; Liu, Changliang; Karakhanyan, Aziz; Kaeser, Pascal S

    2016-08-17

    In a nerve terminal, synaptic vesicle docking and release are restricted to an active zone. The active zone is a protein scaffold that is attached to the presynaptic plasma membrane and opposed to postsynaptic receptors. Here, we generated conditional knockout mice removing the active zone proteins RIM and ELKS, which additionally led to loss of Munc13, Bassoon, Piccolo, and RIM-BP, indicating disassembly of the active zone. We observed a near-complete lack of synaptic vesicle docking and a strong reduction in vesicular release probability and the speed of exocytosis, but total vesicle numbers, SNARE protein levels, and postsynaptic densities remained unaffected. Despite loss of the priming proteins Munc13 and RIM and of docked vesicles, a pool of releasable vesicles remained. Thus, the active zone is necessary for synaptic vesicle docking and to enhance release probability, but releasable vesicles can be localized distant from the presynaptic plasma membrane. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Zizimin and Dock guanine nucleotide exchange factors in cell function and disease.

    Science.gov (United States)

    Pakes, Nicholl K; Veltman, Douwe M; Williams, Robin S B

    2013-01-01

    Zizimin proteins belong to the Dock (Dedicator of Cytokinesis) superfamily of Guanine nucleotide Exchange Factor (GEF) proteins. This family of proteins plays a role in the regulation of Rho family small GTPases. Together the Rho family of small GTPases and the Dock/Zizimin proteins play a vital role in a number of cell processes including cell migration, apoptosis, cell division and cell adhesion. Our recent studies of Zizimin proteins, using a simple biomedical model, the eukaryotic social amoeba Dictyostelium discoideum, have helped to elucidate the cellular role of these proteins. In this article, we discuss the domain structure of Zizimin proteins from an evolutionary viewpoint. We also compare what is currently known about the mammalian Zizimin proteins to that of related Dock proteins. Understanding the cellular functions of these proteins will provide a better insight into their role in cell signaling, and may help in treating disease pathology associated with mutations in Dock/Zizimin proteins.

  13. JL-2: A Mobile Multi-robot System with Docking and Manipulating Capabilities

    Directory of Open Access Journals (Sweden)

    Wei Wang

    2010-03-01

    Full Text Available This paper presents a new version of the JL series reconfigurable multi-robot system called JL-2. By virtue of the docking manipulator composed of a parallel mechanism and a cam gripper, every mobile robot in the JL-2 system is able to not only perform tasks in parallel, e.g. moving and grasping, but also dock with each other even if there are large misalignments between two robots. A motorized spherical joint is formed between two docked robots to enhance the locomotion capability of JL-2. To fulfill the demands of reconfiguration, a distributed control system and sonar based docking guidance system are designed for the JL-2 prototype. Based on the above design, the JL-2 prototype has been built and successfully demonstrated to confirm the validity and functionality of the proposed capabilities.

  14. Post-chemotherapy robotic bilateral retroperitoneal lymph node dissection using a novel single-dock technique.

    Science.gov (United States)

    Stout, Thomas E; Soni, Samit D; Goh, Alvin C

    2016-12-01

    There have been no previous reports of post-chemotherapy robotic bilateral retroperitoneal lymph node dissection (RPLND) using a single-dock technique. One deterrent of robotic RPLND is that accessing bilateral retroperitoneal spaces requires patient reposition and surgical robot redocking, therefore increasing operative time. Herein we provide the first step-by-step description of a single-dock technique for robotic bilateral RPLND in the post-chemotherapy setting. We describe port placement and technique for robot positioning to optimize access to bilateral retroperitoneal spaces with a single dock. We also demonstrate the feasibility of sparing the inferior mesenteric artery when utilizing this approach. This single-dock approach was used on two patients at our institution who had residual paracaval masses following chemotherapy for metastatic testicular cancer. Mean operative time was 6 h, and neither patient had significant blood loss or suffered from any peri-operative complications.

  15. Molecular docking of citrus flavonoids with some targets related to diabetes

    Directory of Open Access Journals (Sweden)

    Wei Shen

    2013-06-01

    Full Text Available Citrus flavonoids isolated from citrus peel (flavedo and albedo were taken as ligands for molecular docking. The molecular targets, (i.e. glucokinase, glycogen synthase kinases 3β, peroxisome proliferator-activated receptor gamma, and dipeptidyl peptidase IV whose crystallographic structures are available on the PDB database as 1V4S, 1Q4L, 2PRG, 2ONC respectively, were used for the docking analysis using the Autodock tool V 4.2 and ADT v1.5.4 programs. The docking studies of the ligands citrus flavonoids with four different target proteins showed that citrus flavonoids are good molecules which dock well with various targets related to diabetes mellitus. The above results demonstrate that citrus flavonoids might be potentially used for blood glucose regulation.

  16. European Proximity Operations Simulator 2.0 (EPOS - A Robotic-Based Rendezvous and Docking Simulator

    Directory of Open Access Journals (Sweden)

    Heike Benninghoff

    2017-04-01

    Full Text Available The European Proximity Operations Simulator (EPOS 2.0 located at the German Space Operations Center (GSOC in Oberpfaffenhofen, Germany, is a robotic based test facility of the German Aerospace Center (DLR used for simulation of rendezvous and docking (RvD processes. Hardware such as rendezvous sensors (cameras, laser scanners or docking tools, as well as software (e.g. for navigation and control can be tested and verified. The facility consists of two robotic manipulators with each six degrees of freedom, a linear slide of 25m length on which one robot can be moved in the laboratory, and a computer-based monitoring and control system. EPOS 2.0 allows for real-time simulations of the rendezvous and docking process during the most critical phase (separation from 25m to 0m of proximity and docking/berthing operations.

  17. In Silico Molecular Docking Analysis of Natural Pyridoacridines as Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Vikas Sharma

    2016-01-01

    Full Text Available Docking studies are proved to be an essential tool that facilitates the structural diversity of natural products to be harnessed in an organized manner. In this study, pyridoacridines containing natural anticancer pigments were subjected to docking studies using Glide (Schrodinger. Investigations were carried out to find out the potential molecular targets for these selected pigments. The docking was carried out on different cancer macromolecules involved in different cell cycle pathways, that is, CDK-2, CDK-6, Bcl-2, VEGFR-2, IGF-1R kinase, and G-Quadruplexes. CDK-6 was found to be the most suitable anticancer target for the pyridoacridines. In addition, effectiveness of the study was further evaluated by performing docking of known inhibitors against their respective selected macromolecules. However, the results are preliminary and experimental evaluation will be carried out in near future.

  18. A Ground Testbed to Advance US Capability in Autonomous Rendezvous and Docking Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The entire Agency supports development of a Commodity for Autonomous Rendezvous and Docking (CARD) as outlined in the Agency-wide Community of Practice whitepaper...

  19. DockAnalyse: an application for the analysis of protein-protein interactions

    Directory of Open Access Journals (Sweden)

    Cedano Juan

    2010-10-01

    Full Text Available Abstract Background Is it possible to identify what the best solution of a docking program is? The usual answer to this question is the highest score solution, but interactions between proteins are dynamic processes, and many times the interaction regions are wide enough to permit protein-protein interactions with different orientations and/or interaction energies. In some cases, as in a multimeric protein complex, several interaction regions are possible among the monomers. These dynamic processes involve interactions with surface displacements between the proteins to finally achieve the functional configuration of the protein complex. Consequently, there is not a static and single solution for the interaction between proteins, but there are several important configurations that also have to be analyzed. Results To extract those representative solutions from the docking output datafile, we have developed an unsupervised and automatic clustering application, named DockAnalyse. This application is based on the already existing DBscan clustering method, which searches for continuities among the clusters generated by the docking output data representation. The DBscan clustering method is very robust and, moreover, solves some of the inconsistency problems of the classical clustering methods like, for example, the treatment of outliers and the dependence of the previously defined number of clusters. Conclusions DockAnalyse makes the interpretation of the docking solutions through graphical and visual representations easier by guiding the user to find the representative solutions. We have applied our new approach to analyze several protein interactions and model the dynamic protein interaction behavior of a protein complex. DockAnalyse might also be used to describe interaction regions between proteins and, therefore, guide future flexible dockings. The application (implemented in the R package is accessible.

  20. Evaluation of the novel algorithm of flexible ligand docking with moveable target-protein atoms.

    Science.gov (United States)

    Sulimov, Alexey V; Zheltkov, Dmitry A; Oferkin, Igor V; Kutov, Danil C; Katkova, Ekaterina V; Tyrtyshnikov, Eugene E; Sulimov, Vladimir B

    2017-01-01

    We present the novel docking algorithm based on the Tensor Train decomposition and the TT-Cross global optimization. The algorithm is applied to the docking problem with flexible ligand and moveable protein atoms. The energy of the protein-ligand complex is calculated in the frame of the MMFF94 force field in vacuum. The grid of precalculated energy potentials of probe ligand atoms in the field of the target protein atoms is not used. The energy of the protein-ligand complex for any given configuration is computed directly with the MMFF94 force field without any fitting parameters. The conformation space of the system coordinates is formed by translations and rotations of the ligand as a whole, by the ligand torsions and also by Cartesian coordinates of the selected target protein atoms. Mobility of protein and ligand atoms is taken into account in the docking process simultaneously and equally. The algorithm is realized in the novel parallel docking SOL-P program and results of its performance for a set of 30 protein-ligand complexes are presented. Dependence of the docking positioning accuracy is investigated as a function of parameters of the docking algorithm and the number of protein moveable atoms. It is shown that mobility of the protein atoms improves docking positioning accuracy. The SOL-P program is able to perform docking of a flexible ligand into the active site of the target protein with several dozens of protein moveable atoms: the native crystallized ligand pose is correctly found as the global energy minimum in the search space with 157 dimensions using 4700 CPU ∗ h at the Lomonosov supercomputer.

  1. International Low Impact Docking System (iLIDS) Project Technical Requirements Specification, Revision F

    Science.gov (United States)

    Lewis, James L.

    2011-01-01

    The NASA Docking System (NDS) is NASA's implementation for the emerging International Docking System Standard (IDSS) using low impact docking technology. The NASA Docking System Project (NDSP) is the International Space Station (ISS) Program's project to produce the NDS, Common Docking Adapter (CDA) and Docking Hub. The NDS design evolved from the Low Impact Docking System (LIDS). The acronym international Low Impact Docking System (iLIDS) is also used to describe this system as well as the Government Furnished Equipment (GFE) project designing the NDS for the NDSP. NDS and iLIDS may be used interchangeability. This document will use the acronym iLIDS. Some of the heritage documentation and implementations (e.g., software command names, requirement identification (ID), figures, etc.) used on NDS will continue to use the LIDS acronym. This specification defines the technical requirements for the iLIDS GFE delivered to the NDSP by the iLIDS project. This document contains requirements for two iLIDS configurations, SEZ29101800-301 and SEZ29101800-302. Requirements with the statement, iLIDS shall, are for all configurations. Examples of requirements that are unique to a single configuration may be identified as iLIDS (-301) shall or iLIDS (-302) shall. Furthermore, to allow a requirement to encompass all configurations with an exception, the requirement may be designated as iLIDS (excluding -302) shall. Verification requirements for the iLIDS project are identified in the Verification Matrix (VM) provided in the iLIDS Verification and Validation Document, JSC-63966. The following definitions differentiate between requirements and other statements: Shall: This is the only verb used for the binding requirements. Should/May: These verbs are used for stating non-mandatory goals. Will: This verb is used for stating facts or declaration of purpose. A Definition of Terms table is provided in Appendix B to define those terms with specific tailored uses in this document.

  2. Structural assembly of two-domain proteins by rigid-body docking

    Directory of Open Access Journals (Sweden)

    Blundell Tom L

    2008-10-01

    Full Text Available Abstract Background Modelling proteins with multiple domains is one of the central challenges in Structural Biology. Although homology modelling has successfully been applied for prediction of protein structures, very often domain-domain interactions cannot be inferred from the structures of homologues and their prediction requires ab initio methods. Here we present a new structural prediction approach for modelling two-domain proteins based on rigid-body domain-domain docking. Results Here we focus on interacting domain pairs that are part of the same peptide chain and thus have an inter-domain peptide region (so called linker. We have developed a method called pyDockTET (tethered-docking, which uses rigid-body docking to generate domain-domain poses that are further scored by binding energy and a pseudo-energy term based on restraints derived from linker end-to-end distances. The method has been benchmarked on a set of 77 non-redundant pairs of domains with available X-ray structure. We have evaluated the docking method ZDOCK, which is able to generate acceptable domain-domain orientations in 51 out of the 77 cases. Among them, our method pyDockTET finds the correct assembly within the top 10 solutions in over 60% of the cases. As a further test, on a subset of 20 pairs where domains were built by homology modelling, ZDOCK generates acceptable orientations in 13 out of the 20 cases, among which the correct assembly is ranked lower than 10 in around 70% of the cases by our pyDockTET method. Conclusion Our results show that rigid-body docking approach plus energy scoring and linker-based restraints are useful for modelling domain-domain interactions. These positive results will encourage development of new methods for structural prediction of macromolecules with multiple (more than two domains.

  3. A novel view of modelling interactions between synthetic and biological polymers via docking

    Science.gov (United States)

    Tsvetkov, Vladimir B.; Serbin, Alexander V.

    2012-12-01

    Multipoint interactions between synthetic and natural polymers provide a promising platform for many topical applications, including therapeutic blockage of virus-specific targets. Docking may become a useful tool for modelling of such interactions. However, the rigid docking cannot be correctly applied to synthetic polymers with flexible chains. The application of flexible docking to these polymers as whole macromolecule ligands is also limited by too many possible conformations. We propose to solve this problem via stepwise flexible docking. Step 1 is docking of separate polymer components: (1) backbone units ( BU), multi-repeated along the chain, and (2) side groups ( SG) consisting of functionally active elements ( SG F ) and bridges ( SG B ) linking SG F with BU. At this step, probable binding sites locations and binding energies for the components are scored. Step 2 is docking of component-integrating models: [ BU] m , SG = SG F -SG B , BU-SG, BU-BU( SG) -BU, BU( SG) -[ BU] m -BU( SG), and [ BU var ( SG var )] m . Every modelling level yields new information, including how the linkage of various components influences on the ligand—target contacts positioning, orientation, and binding energy in step-by-step approximation to polymeric ligand motifs. Step 3 extrapolates the docking results to real-scale macromolecules. This approach has been demonstrated by studying the interactions between hetero-SG modified anionic polymers and the N-heptad repeat region tri-helix core of the human immunodeficiency virus type 1 ( HIV-1) envelope glycoprotein gp41, the key mediator of HIV-1 fusion during virus entry. The docking results are compared to real polymeric compounds, acting as HIV-1 entry inhibitors in vitro. This study clarifies the optimal macromolecular design for the viral fusion inhibition and drug resistance prevention.

  4. 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.

  5. European Proximity Operations Simulator 2.0 (EPOS) - A Robotic-Based Rendezvous and Docking Simulator

    OpenAIRE

    Heike Benninghoff; Florian Rems; Eicke-Alexander Risse; Christian Mietner

    2017-01-01

    The European Proximity Operations Simulator (EPOS) 2.0 located at the German Space Operations Center (GSOC) in Oberpfaffenhofen, Germany, is a robotic based test facility of the German Aerospace Center (DLR) used for simulation of rendezvous and docking (RvD) processes. Hardware such as rendezvous sensors (cameras, laser scanners) or docking tools, as well as software (e.g. for navigation and control) can be tested and verified. The facility consists of two robotic manipulators with each six ...

  6. Biophysical and molecular docking insight into the interaction of cytosine β-D arabinofuranoside with human serum albumin

    Energy Technology Data Exchange (ETDEWEB)

    Alam, Parvez; Chaturvedi, Sumit Kumar [Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, UP (India); Anwar, Tamanna [Center of Bioinformatics Research and Technology, Aligarh 202002 (India); Siddiqi, Mohammad Khursheed; Ajmal, Mohd Rehan [Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, UP (India); Badr, Gamal [Laboratory of Immunology & Molecular Physiology, Zoology Department, Faculty of Science, Assiut University, 71516 Assiut (Egypt); Mahmoud, Mohamed H. [Food Science and Nutrition Department, National Research Center, Dokki, Cairo (Egypt); Deanship of Scientific Research, King Saud University, Riyadh (Saudi Arabia); Hasan Khan, Rizwan, E-mail: rizwanhkhan@hotmail.com [Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh 202002, UP (India)

    2015-08-15

    Interaction of pharmacologically important anticancer drug cytosine β-D arabinofuranoside with human serum albumin (HSA) at physiological pH 7.4 has been studied by utilizing various spectroscopic and molecular docking strategies. Fluorescence results revealed that cytosine β-D arabinofuranoside interacts with HSA through static quenching mechanism with binding affinity of 2.4×10{sup 3} M{sup −1}. The average binding distance between drug and Trp{sup 214} of HSA was found to be 2.23 nm on the basis of the theory of Förster's energy transfer. Synchronous fluorescence data indicated that interaction of drug with HSA changed the microenvironment around the tryptophan residue. UV–visible spectroscopy and circular dichroism results deciphered the complex formation and conformational alterations in the HSA respectively. Dynamic light scattering was utilized to understand the topology of protein in absence and presence of drug. Thermodynamic parameters obtained from isothermal titration calorimetry (ΔH=−26.01 kJ mol{sup −1} and TΔS=6.5 kJ mol{sup −1}) suggested the involvement of van der Waal interaction and hydrogen bonding. Molecular docking and displacement study with site specific markers suggested that cytosine β-D arabinofuranoside binds to subdomain IB of HSA which is also known as the hemin binding site. This study will be helpful to understand the binding mechanism of cytosine β-D arabinofuranoside with HSA and associated alterations. - Highlights: • Comprehensive insight into the interaction of CBDA with HSA. • The interaction process is spontaneous and exothermic. • The main governing forces for stabilizing HSA–CBDA complex are van der Waal interaction and hydrogen bonding. • CBDA binds at subdomain IB on HSA.

  7. Binding of naringin and naringenin with hen egg white lysozyme: A spectroscopic investigation and molecular docking study

    Science.gov (United States)

    Das, Sourav; Ghosh, Pooja; Koley, Sudipta; Singha Roy, Atanu

    2018-03-01

    The interactions of naringenin (NG) and naringin (NR) with Hen Egg White Lysozyme (HEWL) in aqueous medium have been investigated using UV-vis spectroscopy, steady-state fluorescence, circular dichroism (CD), Fourier Transform infrared spectroscopy (FT-IR) and molecular docking analyses. Both NG and NR can quench the intrinsic fluorescence of HEWL via static quenching mechanism. At 300 K, the value of binding constant (Kb) of HEWL-NG complex (5.596 ± 0.063 × 104 M- 1) was found to be greater than that of HEWL-NR complex (3.404 ± 0.407 × 104 M- 1). The negative ΔG° values in cases of both the complexes specify the spontaneous binding. The binding distance between the donor (HEWL) and acceptor (NG/NR) was estimated using the Försters theory and the possibility of non-radiative energy transfer from HEWL to NG/NR was observed. The presence of metal ions (Ca2 +, Cu2 + and Fe2 +) decreased the binding affinity of NG/NR towards HEWL. Synchronous fluorescence studies indicate the change in Trp micro-environment due to the incorporation of NG/NR into HEWL. CD and FT-IR studies indicated that the α-helicity of the HEWL was slightly enhanced due to ligand binding. NG and NR inhibited the enzymatic activity of HEWL and exhibited their affinity for the active site of HEWL. Molecular docking studies revealed that both NG and NR bind in the close vicinity of Trp 62 and Trp 63 residues which is vital for the catalytic activity.

  8. Steroid-Functionalized Titanocenes: Docking Studies with Estrogen Receptor Alpha

    Directory of Open Access Journals (Sweden)

    Li Ming Gao

    2016-11-01

    Full Text Available Estrogen receptor alpha (ERα is a transcription factor that is activated by hormones, with 17β-estradiol being its most active agonist endogenous ligand. ERα is also activated or inactivated by exogenous ligands. ER is overexpressed in hormone-dependent breast cancer, and one of the treatments for this type of cancer is the use of an ER antagonist to halt cell proliferation. We have previously reported four steroid-functionalized titanocenes: pregnenolone, dehydroepiandrosterone (DHEA, trans-androsterone, and androsterone. These steroids have hormonal activity as well as moderate antiproliferative activity, thus these steroids could act as vectors for the titanocene dichloride to target hormone-dependent cancers. Also, these steroids could increase the antiproliferative activity of the resulting titanocenes based on synergism. In order to elucidate which factors contribute to the enhanced antiproliferative activity of these steroid-functionalized titanocenes, we performed docking studies between ERα and the titanocenes and the steroids. The binding affinities and type of bonding interactions of the steroid-functionalized titanocenes with ERα are herein discussed.

  9. Molecular docking, spectroscopic studies and quantum calculations on nootropic drug.

    Science.gov (United States)

    Uma Maheswari, J; Muthu, S; Sundius, Tom

    2014-04-05

    A systematic vibrational spectroscopic assignment and analysis of piracetam [(2-oxo-1-pyrrolidineacetamide)] have been carried out using FT-IR and FT-Raman spectral data. The vibrational analysis was aided by an electronic structure calculation based on the hybrid density functional method B3LYP using a 6-311G++(d,p) basis set. Molecular equilibrium geometries, electronic energies, IR and Raman intensities, and harmonic vibrational frequencies have been computed. The assignments are based on the experimental IR and Raman spectra, and a complete assignment of the observed spectra has been proposed. The UV-visible spectrum of the compound was recorded and the electronic properties, such as HOMO and LUMO energies and the maximum absorption wavelengths λmax were determined by the time-dependent DFT (TD-DFT) method. The geometrical parameters, vibrational frequencies and absorption wavelengths were compared with the experimental data. The complete vibrational assignments are performed on the basis of the potential energy distributions (PED) of the vibrational modes in terms of natural internal coordinates. The simulated FT-IR, FT-Raman, and UV spectra of the title compound have been constructed. Molecular docking studies have been carried out in the active site of piracetam by using Argus Lab. In addition, the potential energy surface, HOMO and LUMO energies, first-order hyperpolarizability and the molecular electrostatic potential have been computed. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. 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.

  11. Molecular Docking and Anticonvulsant Activity of Newly Synthesized Quinazoline Derivatives

    Directory of Open Access Journals (Sweden)

    Hatem A. Abuelizz

    2017-06-01

    Full Text Available A new series of quinazoline-4(3H-ones are evaluated for anticonvulsant activity. After intraperitoneal (ip injection to albino mice at a dose of 100 mg/kg body weight, synthesized quinazolin-4(3H-ones (1–24 were examined in the maximal electroshock (MES induced seizures and subcutaneous pentylenetetrazole (scPTZ induced seizure models in mice. The Rotarod method was applied to determine the neurotoxicity. Most of the compounds displayed anticonvulsant activity in the scPTZ screen at a dose range of 0.204–0.376 mmol/mL. Out of twenty-four, compounds 8, 13 and 19 proved to be the most active with a remarkable protection (100% against PTZ induced convulsions and four times more potent activity than ethosuximide. The structure-activity relationship concluded valuable pharmacophoric information, which was confirmed by the molecular docking studies using the target enzyme human carbon anhydrase II (HCA II. The studied quinazoline analogues suggested that the butyl substitution at position 3 has a significant effect on preventing the spread of seizure discharge and on raising the seizure threshold. However, benzyl substitution at position 3 has shown a strong anticonvulsant activity but with less seizure prevention compared to the butyl substitution.

  12. Spectroscopic, quantum chemical calculation and molecular docking of dipfluzine

    Science.gov (United States)

    Srivastava, Karnica; Srivastava, Anubha; Tandon, Poonam; Sinha, Kirti; Wang, Jing

    2016-12-01

    Molecular structure and vibrational analysis of dipfluzine (C27H29FN2O) were presented using FT-IR and FT-Raman spectroscopy and quantum chemical calculations. The theoretical ground state geometry and electronic structure of dipfluzine are optimized by the DFT/B3LYP/6-311++G (d,p) method and compared with those of the crystal data. The 1D potential energy scan was performed by varying the dihedral angle using B3LYP functional at 6-31G(d,p) level of theory and thus the most stable conformer of the compound were determined. Molecular electrostatic potential surface (MEPS), frontier orbital analysis and electronic reactivity descriptor were used to predict the chemical reactivity of molecule. Energies of intra- and inter-molecular hydrogen bonds in molecule and their electronic aspects were investigated by natural bond orbital (NBO). To find out the anti-apoptotic activity of the title compound molecular docking studies have been performed against protein Fas.

  13. Himalayan dock (Rumex nepalensis): the flip side of obnoxious weed.

    Science.gov (United States)

    Wangchuk, Kesang

    2015-01-01

    Himalayan dock (Rumex nepalensis) was evaluated for forage value and antinutrients under three, five and seven weeks cutting intervals in the temperate environment. Dry matter (DM) content was measured for each cutting interval. Forage quality parameters such as Crude Protein (CP), Acid Detergent fiber (ADF), Neutral Detergent Fiber (NDF), Calcium (Ca) and Phosphorus (P) were analyzed. Plants with seven weeks cutting interval gave higher DM yield. CP and P content were significantly higher for three weeks cutting intervals. Average CP contents were 31.38 %, 30.73 % and 27.32 % and average P content 0.58 %, 0.52 % and 0.51 % for three, five and seven weeks cutting intervals, respectively. Ca content did not differ significantly between cutting intervals. The average Ca content were 0.91 %, 0.90 % and 90 %, for three, five and seven weeks cutting intervals, respectively. Tannin and mimosine contents were not significantly different between cutting intervals. Average tannin contents were 1.32 %, 1.27 % and 1.26 % and mimosine 0.38 %, 0.30 % and 0.28 % for three, five and seven weeks cutting intervals, respectively. The study concluded that R. nepalensis could be a potential source of protein for livestock. The study also suggests seven weeks harvesting interval to provide plants with high dry matter yield, high forage quality and very low levels of anti-nutrients.

  14. Identification of Novel Smoothened Ligands Using Structure-Based Docking.

    Directory of Open Access Journals (Sweden)

    Celine Lacroix

    Full Text Available The seven transmembrane protein Smoothened is required for Hedgehog signaling during embryonic development and adult tissue homeostasis. Inappropriate activation of the Hedgehog signalling pathway leads to cancers such as basal cell carcinoma and medulloblastoma, and Smoothened inhibitors are now available clinically to treat these diseases. However, resistance to these inhibitors rapidly develops thereby limiting their efficacy. The determination of Smoothened crystal structures enables structure-based discovery of new ligands with new chemotypes that will be critical to combat resistance. In this study, we docked 3.2 million available, lead-like molecules against Smoothened, looking for those with high physical complementarity to its structure; this represents the first such campaign against the class Frizzled G-protein coupled receptor family. Twenty-one high-ranking compounds were selected for experimental testing, and four, representing three different chemotypes, were identified to antagonize Smoothened with IC50 values better than 50 μM. A screen for analogs revealed another six molecules, with IC50 values in the low micromolar range. Importantly, one of the most active of the new antagonists continued to be efficacious at the D473H mutant of Smoothened, which confers clinical resistance to the antagonist vismodegib in cancer treatment.

  15. Peptides Trapping Dioxins: A Docking-Based Inverse Screening Approach

    Directory of Open Access Journals (Sweden)

    German Perez

    2013-01-01

    Full Text Available A rapid and cost-effective computational methodology for designing and rationalizing the selection of small peptides as receptors for dioxin-like compounds was proposed. The backbone of the dioxin Ah receptor binding site was used to design a series of penta- and hexapeptide libraries, with 1400 elements in total. Peptide flexibility was considered and 10 conformers were found to be a good option to represent peptide conformational space with fair speed-accuracy ratio. Each peptide conformer was treated as a possible receptor, generating a dedicated box and then running a docking process using as ligands a family of 76 dibenzo-p-dioxins and 113 dibenzofurans mono- and polychlorinated. Significant predictions were confirmed by comparing primary structure of top and bottom ranked peptides binding dioxins confirming that scrambled positions of the same amino acids gave completely different predicted binding. The hexapeptide EWFQPW, with the best binding score, was chosen as selective sorbent material in solid-phase extraction. The retention performances were tested using the 2,3,7,8-tetrachlorodibenzo-p-dioxin and two polychlorinated biphenyls in order to verify the hexapeptide specificity. The solid-phase extraction experimental procedure was optimized, and analytical parameters of hexapeptide sorbent material were compared with the resin without hexapeptide and a commercial reversed phase cartridge.

  16. Spectroscopic, structural and drug docking studies of carbocysteine

    Science.gov (United States)

    Manivannan, M.; Rajeshwaran, K.; Govindhan, R.; Karthikeyan, B.

    2017-09-01

    Carbocysteine or carbocisteine having the empirical formula C5H9NO4S,is one of the most therapeutically prescribed expectorant, sold under the brand name viz., Mucodyne (UK and India), Rhinathiol and Mucolite. In pediatric respiratory pathology, it can relieve the symptoms of obstructive pulmonary disease (COPD) and bronchiectasis. On the consideration of its extensive pharmaceutical usage and medicinal value, we have investigated its chemical structure and composition by employing various spectral techniques like 1H, 13C NMR, FT-IR,Raman, UV-Visible spectroscopy and powder X-ray diffraction method. Density Functional Theoretical (DFT) studies on its electronic structure is also carried out. Drug docking studies were carried out to ascertain the nature of molecular interaction with the biological protein system. Furthermore theoretical Raman spectrum of this molecule has been computed and compared with the experimental Raman spectrum. The forbidden energy gap between its frontier molecular orbitals, viz., HOMO-LUMO is calculated and correlated with its observed λmax value. Atomic orbitals which are mainly contributes to the frontier molecular orbitals were identified. Molecular electrostatic potential diagram has been mapped to explain its chemical activity. Based on the results, a suitable mechanism of its protein binding mode and drug action has been discussed.

  17. Assessment of the transmembrane domain structures in GPCR Dock 2013 models.

    Science.gov (United States)

    Wang, Ting; Liu, Haiguang; Duan, Yong

    2018-03-01

    The community-wide blind prediction of G-protein coupled receptor (GPCR) structures and ligand docking has been conducted three times and the quality of the models was primarily assessed by the accuracy of ligand binding modes. The seven transmembrane (TM) helices of the receptors were taken as a whole; thus the model quality within the 7TM domains has not been evaluated. Here we evaluate the 7TM domain structures in the models submitted for the last round of prediction - GPCR Dock 2013. Applying the 7 × 7 RMSD matrix analysis described in our prior work, we show that the models vary widely in prediction accuracy of the 7TM structures, exhibiting diverse structural differences from the targets. For the prediction of the 5-hydroxytryptamine receptors, the top 7TM models are rather close to the targets, which however are not ranked top by ligand-docking. On the other hand, notable deviations of the TMs are found in in the previously identified top docking models that closely resemble other receptors. We further reveal reasons of success and failure in ligand docking for the models. This current assessment not only complements the previous assessment, but also provides important insights into the current status of GPCR modeling and ligand docking. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Accelerating protein docking in ZDOCK using an advanced 3D convolution library.

    Science.gov (United States)

    Pierce, Brian G; Hourai, Yuichiro; Weng, Zhiping

    2011-01-01

    Computational prediction of the 3D structures of molecular interactions is a challenging area, often requiring significant computational resources to produce structural predictions with atomic-level accuracy. This can be particularly burdensome when modeling large sets of interactions, macromolecular assemblies, or interactions between flexible proteins. We previously developed a protein docking program, ZDOCK, which uses a fast Fourier transform to perform a 3D search of the spatial degrees of freedom between two molecules. By utilizing a pairwise statistical potential in the ZDOCK scoring function, there were notable gains in docking accuracy over previous versions, but this improvement in accuracy came at a substantial computational cost. In this study, we incorporated a recently developed 3D convolution library into ZDOCK, and additionally modified ZDOCK to dynamically orient the input proteins for more efficient convolution. These modifications resulted in an average of over 8.5-fold improvement in running time when tested on 176 cases in a newly released protein docking benchmark, as well as substantially less memory usage, with no loss in docking accuracy. We also applied these improvements to a previous version of ZDOCK that uses a simpler non-pairwise atomic potential, yielding an average speed improvement of over 5-fold on the docking benchmark, while maintaining predictive success. This permits the utilization of ZDOCK for more intensive tasks such as docking flexible molecules and modeling of interactomes, and can be run more readily by those with limited computational resources.

  19. 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.

  20. Accelerating protein docking in ZDOCK using an advanced 3D convolution library.

    Directory of Open Access Journals (Sweden)

    Brian G Pierce

    Full Text Available Computational prediction of the 3D structures of molecular interactions is a challenging area, often requiring significant computational resources to produce structural predictions with atomic-level accuracy. This can be particularly burdensome when modeling large sets of interactions, macromolecular assemblies, or interactions between flexible proteins. We previously developed a protein docking program, ZDOCK, which uses a fast Fourier transform to perform a 3D search of the spatial degrees of freedom between two molecules. By utilizing a pairwise statistical potential in the ZDOCK scoring function, there were notable gains in docking accuracy over previous versions, but this improvement in accuracy came at a substantial computational cost. In this study, we incorporated a recently developed 3D convolution library into ZDOCK, and additionally modified ZDOCK to dynamically orient the input proteins for more efficient convolution. These modifications resulted in an average of over 8.5-fold improvement in running time when tested on 176 cases in a newly released protein docking benchmark, as well as substantially less memory usage, with no loss in docking accuracy. We also applied these improvements to a previous version of ZDOCK that uses a simpler non-pairwise atomic potential, yielding an average speed improvement of over 5-fold on the docking benchmark, while maintaining predictive success. This permits the utilization of ZDOCK for more intensive tasks such as docking flexible molecules and modeling of interactomes, and can be run more readily by those with limited computational resources.

  1. 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.

  2. Starfish ApDOCK protein essentially functions in larval defense system operated by mesenchyme cells.

    Science.gov (United States)

    Furukawa, Ryohei; Funabashi, Hiromi; Matsumoto, Midori; Kaneko, Hiroyuki

    2012-11-01

    In larvae of the starfish, Asterina pectinifera, mesenchyme cells operate in the defense system through various behaviors. We have investigated mesenchyme cell dynamics during the immune response by identifying ApDOCK, a new member of the DOCK180 superfamily protein. In 4-day-old bipinnaria larvae processed for morpholino oligonucleotide-mediated knockdown of ApDOCK, injection of inorganic foreign substances revealed that (1) mesenchyme cells fail to undergo either directed migration toward a large oil-droplet or persistent spreading on the oil-droplet after contact; (2) neither uptake of micro-beads nor cell-to-cell fusion on the large oil-droplet differed from that of mesenchyme cells from control larvae. Similar behaviors were also recorded in experiments where bacteria were injected. Under culture conditions, the expression level of ApDOCK mRNA was significantly associated with the immunological behavior of mesenchyme cells. Apparently, the mesenchyme cells from ApDOCK loss-of-function larvae exhibited insufficient lamellipodium formation via lack of fibrous form of actin organization at the leading edge. These results suggest that the migratory congregation and persistence of encapsulation of larval mesenchyme cells are intracellularly regulated by ApDOCK protein, and this regulation is associated with organization of cytoskeletal actin.

  3. Targeting Ras-Driven Cancer Cell Survival and Invasion through Selective Inhibition of DOCK1

    Directory of Open Access Journals (Sweden)

    Hirotada Tajiri

    2017-05-01

    Full Text Available Oncogenic Ras plays a key role in cancer initiation but also contributes to malignant phenotypes by stimulating nutrient uptake and promoting invasive migration. Because these latter cellular responses require Rac-mediated remodeling of the actin cytoskeleton, we hypothesized that molecules involved in Rac activation may be valuable targets for cancer therapy. We report that genetic inactivation of the Rac-specific guanine nucleotide exchange factor DOCK1 ablates both macropinocytosis-dependent nutrient uptake and cellular invasion in Ras-transformed cells. By screening chemical libraries, we have identified 1-(2-(3′-(trifluoromethyl-[1,1′-biphenyl]-4-yl-2-oxoethyl-5-pyrrolidinylsulfonyl-2(1H-pyridone (TBOPP as a selective inhibitor of DOCK1. TBOPP dampened DOCK1-mediated invasion, macropinocytosis, and survival under the condition of glutamine deprivation without impairing the biological functions of the closely related DOCK2 and DOCK5 proteins. Furthermore, TBOPP treatment suppressed cancer metastasis and growth in vivo in mice. Our results demonstrate that selective pharmacological inhibition of DOCK1 could be a therapeutic approach to target cancer cell survival and invasion.

  4. A cross docking pipeline for improving pose prediction and virtual screening performance

    Science.gov (United States)

    Kumar, Ashutosh; Zhang, Kam Y. J.

    2017-08-01

    Pose prediction and virtual screening performance of a molecular docking method depend on the choice of protein structures used for docking. Multiple structures for a target protein are often used to take into account the receptor flexibility and problems associated with a single receptor structure. However, the use of multiple receptor structures is computationally expensive when docking a large library of small molecules. Here, we propose a new cross-docking pipeline suitable to dock a large library of molecules while taking advantage of multiple target protein structures. Our method involves the selection of a suitable receptor for each ligand in a screening library utilizing ligand 3D shape similarity with crystallographic ligands. We have prospectively evaluated our method in D3R Grand Challenge 2 and demonstrated that our cross-docking pipeline can achieve similar or better performance than using either single or multiple-receptor structures. Moreover, our method displayed not only decent pose prediction performance but also better virtual screening performance over several other methods.

  5. The Drosophila DOCK family protein Sponge is required for development of the air sac primordium.

    Science.gov (United States)

    Morishita, Kazushge; Anh Suong, Dang Ngoc; Yoshida, Hideki; Yamaguchi, Masamitsu

    2017-05-15

    Dedicator of cytokinesis (DOCK) family genes are known as DOCK1-DOCK11 in mammals. DOCK family proteins mainly regulate actin filament polymerization and/or depolymerization and are GEF proteins, which contribute to cellular signaling events by activating small G proteins. Sponge (Spg) is a Drosophila counterpart to mammalian DOCK3/DOCK4, and plays a role in embryonic central nervous system development, R7 photoreceptor cell differentiation, and adult thorax development. In order to conduct further functional analyses on Spg in vivo, we examined its localization in third instar larval wing imaginal discs. Immunostaining with purified anti-Spg IgG revealed that Spg mainly localized in the air sac primordium (ASP) in wing imaginal discs. Spg is therefore predicted to play an important role in the ASP. The specific knockdown of Spg by the breathless-GAL4 driver in tracheal cells induced lethality accompanied with a defect in ASP development and the induction of apoptosis. The monitoring of ERK signaling activity in wing imaginal discs by immunostaining with anti-diphospho-ERK IgG revealed reductions in the ERK signal cascade in Spg knockdown clones. Furthermore, the overexpression of D-raf suppressed defects in survival and the proliferation of cells in the ASP induced by the knockdown of Spg. Collectively, these results indicate that Spg plays a critical role in ASP development and tracheal cell viability that is mediated by the ERK signaling pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Using robotics to fold proteins and dock ligands.

    Science.gov (United States)

    Brutlag, Douglas; Apaydin, Serkan; Guestrin, Carlos; Hsu, David; Varma, Chris; Singh, Amit; Latombe, Jean-Claude

    2002-01-01

    The problems of protein folding and ligand docking have been explored largely using molecular dynamics or Monte Carlo methods. These methods are very compute intensive because they often explore a much wider range of energies, conformations and time than necessary. In addition, Monte Carlo methods often get trapped in local minima. We initially showed that robotic motion planning permitted one to determine the energy of binding and dissociation of ligands from protein binding sites (Singh et al., 1999). The robotic motion planning method maps complicated three-dimensional conformational states into a much simpler, but higher dimensional space in which conformational rearrangements can be represented as linear paths. The dimensionality of the conformation space is of the same order as the number of degrees of conformational freedom in three-dimensional space. We were able to determine the relative energy of association and dissociation of a ligand to a protein by calculating the energetics of interaction for a few thousand conformational states in the vicinity of the protein and choosing the best path from the roadmap. More recently, we have applied roadmap planning to the problem of protein folding (Apaydin et al., 2002a). We represented multiple conformations of a protein as nodes in a compact graph with the edges representing the probability of moving between neighboring states. Instead of using Monte Carlo simulation to simulate thousands of possible paths through various conformational states, we were able to use Markov methods to calculate the steady state occupancy of each conformation, needing to calculate the energy of each conformation only once. We referred to this Markov method of representing multiple conformations and transitions as stochastic roadmap simulation or SRS. We demonstrated that the distribution of conformational states calculated with exhaustive Monte Carlo simulations asymptotically approached the Markov steady state if the same Boltzman

  7. 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.

  8. Use of the FACTS solvation model for protein-ligand docking calculations. Application to EADock.

    Science.gov (United States)

    Zoete, Vincent; Grosdidier, Aurélien; Cuendet, Michel; Michielin, Olivier

    2010-01-01

    Protein-ligand docking has made important progress during the last decade and has become a powerful tool for drug development, opening the way to virtual high throughput screening and in silico structure-based ligand design. Despite the flattering picture that has been drawn, recent publications have shown that the docking problem is far from being solved, and that more developments are still needed to achieve high successful prediction rates and accuracy. Introducing an accurate description of the solvation effect upon binding is thought to be essential to achieve this goal. In particular, EADock uses the Generalized Born Molecular Volume 2 (GBMV2) solvent model, which has been shown to reproduce accurately the desolvation energies calculated by solving the Poisson equation. Here, the implementation of the Fast Analytical Continuum Treatment of Solvation (FACTS) as an implicit solvation model in small molecules docking calculations has been assessed using the EADock docking program. Our results strongly support the use of FACTS for docking. The success rates of EADock/FACTS and EADock/GBMV2 are similar, i.e. around 75% for local docking and 65% for blind docking. However, these results come at a much lower computational cost: FACTS is 10 times faster than GBMV2 in calculating the total electrostatic energy, and allows a speed up of EADock by a factor of 4. This study also supports the EADock development strategy relying on the CHARMM package for energy calculations, which enables straightforward implementation and testing of the latest developments in the field of Molecular Modeling.

  9. Marine dock pilings foster diverse, native cryptobenthic fish assemblages across bioregions.

    Science.gov (United States)

    Brandl, Simon J; Casey, Jordan M; Knowlton, Nancy; Duffy, James Emmett

    2017-09-01

    Anthropogenic habitats are increasingly prevalent in coastal marine environments. Previous research on sessile epifauna suggests that artificial habitats act as a refuge for nonindigenous species, which results in highly homogenous communities across locations. However, vertebrate assemblages that live in association with artificial habitats are poorly understood. Here, we quantify the biodiversity of small, cryptic (henceforth "cryptobenthic") fishes from marine dock pilings across six locations over 35° of latitude from Maine to Panama. We also compare assemblages from dock pilings to natural habitats in the two southernmost locations (Panama and Belize). Our results suggest that the biodiversity patterns of cryptobenthic fishes from dock pilings follow a Latitudinal Diversity Gradient (LDG), with average local and regional diversity declining sharply with increasing latitude. Furthermore, a strong correlation between community composition and spatial distance suggests distinct regional assemblages of cryptobenthic fishes. Cryptobenthic fish assemblages from dock pilings in Belize and Panama were less diverse and had lower densities than nearby reef habitats. However, dock pilings harbored almost exclusively native species, including two species of conservation concern absent from nearby natural habitats. Our results suggest that, in contrast to sessile epifaunal assemblages on artificial substrates, artificial marine habitats can harbor diverse, regionally characteristic assemblages of vertebrates that follow macroecological patterns that are well documented for natural habitats. We therefore posit that, although dock pilings cannot function as a replacement for natural habitats, dock pilings may provide cost-effective means to preserve native vertebrate biodiversity, and provide a habitat that can be relatively easily monitored to track the status and trends of fish biodiversity in highly urbanized coastal marine environments.

  10. Calculating an optimal box size for ligand docking and virtual screening against experimental and predicted binding pockets.

    Science.gov (United States)

    Feinstein, Wei P; Brylinski, Michal

    2015-01-01

    Computational approaches have emerged as an instrumental methodology in modern research. For example, virtual screening by molecular docking is routinely used in computer-aided drug discovery. One of the critical parameters for ligand docking is the size of a search space used to identify low-energy binding poses of drug candidates. Currently available docking packages often come with a default protocol for calculating the box size, however, many of these procedures have not been systematically evaluated. In this study, we investigate how the docking accuracy of AutoDock Vina is affected by the selection of a search space. We propose a new procedure for calculating the optimal docking box size that maximizes the accuracy of binding pose prediction against a non-redundant and representative dataset of 3,659 protein-ligand complexes selected from the Protein Data Bank. Subsequently, we use the Directory of Useful Decoys, Enhanced to demonstrate that the optimized docking box size also yields an improved ranking in virtual screening. Binding pockets in both datasets are derived from the experimental complex structures and, additionally, predicted by eFindSite. A systematic analysis of ligand binding poses generated by AutoDock Vina shows that the highest accuracy is achieved when the dimensions of the search space are 2.9 times larger than the radius of gyration of a docking compound. Subsequent virtual screening benchmarks demonstrate that this optimized docking box size also improves compound ranking. For instance, using predicted ligand binding sites, the average enrichment factor calculated for the top 1 % (10 %) of the screening library is 8.20 (3.28) for the optimized protocol, compared to 7.67 (3.19) for the default procedure. Depending on the evaluation metric, the optimal docking box size gives better ranking in virtual screening for about two-thirds of target proteins. This fully automated procedure can be used to optimize docking protocols in order to

  11. Homology modeling and molecular docking studies of Bacillomycin and Iturin synthetases with novel ligands for the production of therapeutic lipopeptides.

    Science.gov (United States)

    Eswari, Jujjavarapu Satya; Dhagat, Swasti; Kaser, Shubham; Tiwari, Anoop

    2017-08-15

    Lipopeptide synthetases play an important role in the production of lipopeptides. Lipopeptides are molecules made up of peptides and fatty acid moieties and have shown to have a broad range of antimicrobial activity. As infectious diseases have caused severe health problems mainly resulting from the development of antibiotic resistant strains of disease causing microorganisms there is a need of alternatives to antibiotics. The lipopeptide synthetase of the corresponding lipopeptides can be used as templates to design these as drugs using computational techniques. The objective of this study was homology modeling and molecular docking of two lipopeptide synthetases, bacillomycin D synthetase and iturin A synthetase, with their ligands as a means of drug design. Schrödinger software was used for homology modeling and molecular docking. After the identification of ligands, molecular docking of these ligands with the lipopeptide (bacillomycin and iturin) synthetases was performed. The docking was tested on the parameters of docking score and glide energy. 5 out of 21 ligands were found to dock with bacillomycin D synthetase whereas 8 out of 20 ligands docked with the iturin A synthetase. The knowledge of the docking sites and docking characteristics of the lipopeptide synthetases mentioned in the paper with the ligands can provide advantages of high speed and reliability, reduced costs on chemicals and experiments and the ethical issues concerned with the use of animal models for screening of drug toxicity. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. A benchmark testing ground for integrating homology modeling and protein docking.

    Science.gov (United States)

    Bohnuud, Tanggis; Luo, Lingqi; Wodak, Shoshana J; Bonvin, Alexandre M J J; Weng, Zhiping; Vajda, Sandor; Schueler-Furman, Ora; Kozakov, Dima

    2017-01-01

    Protein docking procedures carry out the task of predicting the structure of a protein-protein complex starting from the known structures of the individual protein components. More often than not, however, the structure of one or both components is not known, but can be derived by homology modeling on the basis of known structures of related proteins deposited in the Protein Data Bank (PDB). Thus, the problem is to develop methods that optimally integrate homology modeling and docking with the goal of predicting the structure of a complex directly from the amino acid sequences of its component proteins. One possibility is to use the best available homology modeling and docking methods. However, the models built for the individual subunits often differ to a significant degree from the bound conformation in the complex, often much more so than the differences observed between free and bound structures of the same protein, and therefore additional conformational adjustments, both at the backbone and side chain levels need to be modeled to achieve an accurate docking prediction. In particular, even homology models of overall good accuracy frequently include localized errors that unfavorably impact docking results. The predicted reliability of the different regions in the model can also serve as a useful input for the docking calculations. Here we present a benchmark dataset that should help to explore and solve combined modeling and docking problems. This dataset comprises a subset of the experimentally solved 'target' complexes from the widely used Docking Benchmark from the Weng Lab (excluding antibody-antigen complexes). This subset is extended to include the structures from the PDB related to those of the individual components of each complex, and hence represent potential templates for investigating and benchmarking integrated homology modeling and docking approaches. Template sets can be dynamically customized by specifying ranges in sequence similarity and in

  13. Facilitating Transfers

    DEFF Research Database (Denmark)

    Kjær, Poul F.

    to specific logics of temporalisation and spatial expansion of a diverse set of social processes in relation to, for example, the economy, politics, science and the mass media. On this background, the paper will more concretely develop a conceptual framework for classifying different contextual orders......The concept of governance has mutated into an all‐embracing buzz‐word characterised by a low degree of conceptual precision and empirical focus. This paper therefore suggests a narrower and more precise understanding of governance and the regulatory function it fulfils by advancing the argument...... that the essential functional and normative purpose of regulatory governance is to facilitate, stabilise and justify the transfer of condensed social components (such as economic capital and products, political decisions, legal judgements, religious beliefs and scientific knowledge) from one social contexts...

  14. Synthesis of 4-aminophenyl substituted indole derivatives for the instrumental analysis and molecular docking evaluation studies

    Science.gov (United States)

    Singh, Navneet; Kumar, Keshav

    2017-07-01

    The Indole has been known to maintain celebrity status since so many decades and has been a centre point at the spectrum of pharmacological research. The present work stimulates an idea of generating a pool of library of lead compounds. The data collected can be used for the mapping of biologically active compounds. The reported derivatives of 4-aminophenyl substituted Indole were prepared by the methods of Fischer Indole synthesis and Vilsemeier reaction followed by screening for instrumental analysis and molecular docking studies. The synthesized compounds 4-(1-(2-phenylhydrazono)ethyl)aniline, 1, 4-(1H-indol-2-yl)aniline, 2 and 2-(4-aminophenyl)-1H-indole-3-carbaldehyde, 3 were found to have remarkable yield and instrumental data analysis and also showed remarkable docked characteristic. The molecular docking studies revealed that ligand (amino acids) of comp. 1, 2 and 3 had been docked successfully on the binding site of the 3JUS protein selected from PDB with H bonding. The molecular docking data showed that compound 1, would possess remarkable biological activity and compd. 2 and 3 would possess mild to moderate biological activity. Thus this research work paves the way to synthesize new derivatives and thus to develop new compounds in future with accurate prediction.

  15. A non-redundant protein-RNA docking benchmark version 2.0.

    Science.gov (United States)

    Nithin, Chandran; Mukherjee, Sunandan; Bahadur, Ranjit Prasad

    2017-02-01

    We present an updated version of the protein-RNA docking benchmark, which we first published four years back. The non-redundant protein-RNA docking benchmark version 2.0 consists of 126 test cases, a threefold increase in number compared to its previous version. The present version consists of 21 unbound-unbound cases, of which, in 12 cases, the unbound RNAs are taken from another complex. It also consists of 95 unbound-bound cases where only the protein is available in the unbound state. Besides, we introduce 10 new bound-unbound cases where only the RNA is found in the unbound state. Based on the degree of conformational change of the interface residues upon complex formation the benchmark is classified into 72 rigid-body cases, 25 semiflexible cases and 19 full flexible cases. It also covers a wide range of conformational flexibility including small side chain movement to large domain swapping in protein structures as well as flipping and restacking in RNA bases. This benchmark should provide the docking community with more test cases for evaluating rigid-body as well as flexible docking algorithms. Besides, it will also facilitate the development of new algorithms that require large number of training set. The protein-RNA docking benchmark version 2.0 can be freely downloaded from http://www.csb.iitkgp.ernet.in/applications/PRDBv2. Proteins 2017; 85:256-267. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Assessing an ensemble docking-based virtual screening strategy for kinase targets by considering protein flexibility.

    Science.gov (United States)

    Tian, Sheng; Sun, Huiyong; Pan, Peichen; Li, Dan; Zhen, Xuechu; Li, Youyong; Hou, Tingjun

    2014-10-27

    In this study, to accommodate receptor flexibility, based on multiple receptor conformations, a novel ensemble docking protocol was developed by using the naïve Bayesian classification technique, and it was evaluated in terms of the prediction accuracy of docking-based virtual screening (VS) of three important targets in the kinase family: ALK, CDK2, and VEGFR2. First, for each target, the representative crystal structures were selected by structural clustering, and the capability of molecular docking based on each representative structure to discriminate inhibitors from non-inhibitors was examined. Then, for each target, 50 ns molecular dynamics (MD) simulations were carried out to generate an ensemble of the conformations, and multiple representative structures/snapshots were extracted from each MD trajectory by structural clustering. On average, the representative crystal structures outperform the representative structures extracted from MD simulations in terms of the capabilities to separate inhibitors from non-inhibitors. Finally, by using the naïve Bayesian classification technique, an integrated VS strategy was developed to combine the prediction results of molecular docking based on different representative conformations chosen from crystal structures and MD trajectories. It was encouraging to observe that the integrated VS strategy yields better performance than the docking-based VS based on any single rigid conformation. This novel protocol may provide an improvement over existing strategies to search for more diverse and promising active compounds for a target of interest.

  17. A conservation and biophysics guided stochastic approach to refining docked multimeric proteins.

    Science.gov (United States)

    Akbal-Delibas, Bahar; Haspel, Nurit

    2013-01-01

    We introduce a protein docking refinement method that accepts complexes consisting of any number of monomeric units. The method uses a scoring function based on a tight coupling between evolutionary conservation, geometry and physico-chemical interactions. Understanding the role of protein complexes in the basic biology of organisms heavily relies on the detection of protein complexes and their structures. Different computational docking methods are developed for this purpose, however, these methods are often not accurate and their results need to be further refined to improve the geometry and the energy of the resulting complexes. Also, despite the fact that complexes in nature often have more than two monomers, most docking methods focus on dimers since the computational complexity increases exponentially due to the addition of monomeric units. Our results show that the refinement scheme can efficiently handle complexes with more than two monomers by biasing the results towards complexes with native interactions, filtering out false positive results. Our refined complexes have better IRMSDs with respect to the known complexes and lower energies than those initial docked structures. Evolutionary conservation information allows us to bias our results towards possible functional interfaces, and the probabilistic selection scheme helps us to escape local energy minima. We aim to incorporate our refinement method in a larger framework which also enables docking of multimeric complexes given only monomeric structures.

  18. Computational Docking of Antibody-Antigen Complexes, Opportunities and Pitfalls Illustrated by Influenza Hemagglutinin

    Directory of Open Access Journals (Sweden)

    Mattia Pedotti

    2011-01-01

    Full Text Available Antibodies play an increasingly important role in both basic research and the pharmaceutical industry. Since their efficiency depends, in ultimate analysis, on their atomic interactions with an antigen, studying such interactions is important to understand how they function and, in the long run, to design new molecules with desired properties. Computational docking, the process of predicting the conformation of a complex from its separated components, is emerging as a fast and affordable technique for the structural characterization of antibody-antigen complexes. In this manuscript, we first describe the different computational strategies for the modeling of antibodies and docking of their complexes, and then predict the binding of two antibodies to the stalk region of influenza hemagglutinin, an important pharmaceutical target. The purpose is two-fold: on a general note, we want to illustrate the advantages and pitfalls of computational docking with a practical example, using different approaches and comparing the results to known experimental structures. On a more specific note, we want to assess if docking can be successful in characterizing the binding to the same influenza epitope of other antibodies with unknown structure, which has practical relevance for pharmaceutical and biological research. The paper clearly shows that some of the computational docking predictions can be very accurate, but the algorithm often fails to discriminate them from inaccurate solutions. It is of paramount importance, therefore, to use rapidly obtained experimental data to validate the computational results.

  19. DockScreen: A Database of In Silico Biomolecular Interactions to Support Computational Toxicology

    Directory of Open Access Journals (Sweden)

    Michael-Rock Goldsmith

    2014-01-01

    Full Text Available We have developed DockScreen, a database of in silico biomolecular interactions designed to enable rational molecular toxicological insight within a computational toxicology framework. This database is composed of chemical/target (receptor and enzyme binding scores calculated by molecular docking of more than 1000 chemicals into 150 protein targets and contains nearly 135 thousand unique ligand/target binding scores. Obtaining this dataset was achieved using eHiTS (Simbiosys Inc., a fragment-based molecular docking approach with an exhaustive search algorithm, on a heterogeneous distributed high-performance computing framework. The chemical landscape covered in DockScreen comprises selected environmental and therapeutic chemicals. The target landscape covered in DockScreen was selected based on the availability of high-quality crystal structures that covered the assay space of phase I ToxCast in vitro assays. This in silico data provides continuous information that establishes a means for quantitatively comparing, on a structural biophysical basis, a chemical’s profile of biomolecular interactions. The combined minimum-score chemical/target matrix is provided.

  20. Productivity and abundance of bacteria and phytoplankton in Incheon Dock, western coast of Korea.

    Science.gov (United States)

    Yoo, Jong Su

    2008-07-01

    The monthly variations of abundance and productivity of bacteria and phytoplankton were investigated in 2002 at Incheon Dock in Korea, almost closed marine ecosystem. Incheon Dock has unique marine environment with scarcely a current and waves such as in a lake. The bacterial abundance was 0.4-6.3 x 10(6) cells x ml(-1), while the bacterial productivity showed in the range of 0.7-26.3 mgC m(-3) hr(-1). The phytoplankton chlorophyll-a concentrations fell between 2.1 and 18.1 microg x l(-1), where nanoplankton fractions contributed in 32.5-96.78% (average: 73.2%). The algal bloom occurred in March and August, and primary productivity measured by using 14C method, showed a fluctuation ranging from 49.4 to 4,359.4 mgC m(-2) day(-1). The primary productivity of nanotoplankton accounted for 79% of total phytoplankton. Meanwhile, the ratio of bacterial productivity over primary productivity was between 2.0 and 7.7. This study showed that the abundance and productivity of bacteria and phytoplankton were higher at Incheon Dock than those at other coastal areas in Korea. Especially the assimilation number was higher at Incheon Dock than that at lake Shihwa which is a severely eutrophicated area. This result indicates that Incheon Dock has unique ecosystem oceanographically and topographically and it differs from other coastal areas in terms of the low trophic level organisms being abundant and highly productive.

  1. Dock/Nck facilitates PTP61F/PTP1B regulation of insulin signalling.

    Science.gov (United States)

    Wu, Chia-Lun; Buszard, Bree; Teng, Chun-Hung; Chen, Wei-Lin; Warr, Coral G; Tiganis, Tony; Meng, Tzu-Ching

    2011-10-01

    PTP1B (protein tyrosine phosphatase 1B) is a negative regulator of IR (insulin receptor) activation and glucose homoeostasis, but the precise molecular mechanisms governing PTP1B substrate selectivity and the regulation of insulin signalling remain unclear. In the present study we have taken advantage of Drosophila as a model organism to establish the role of the SH3 (Src homology 3)/SH2 adaptor protein Dock (Dreadlocks) and its mammalian counterpart Nck in IR regulation by PTPs. We demonstrate that the PTP1B orthologue PTP61F dephosphorylates the Drosophila IR in S2 cells in vitro and attenuates IR-induced eye overgrowth in vivo. Our studies indicate that Dock forms a stable complex with PTP61F and that Dock/PTP61F associate with the IR in response to insulin. We report that Dock is required for effective IR dephosphorylation and inactivation by PTP61F in vitro and in vivo. Furthermore, we demonstrate that Nck interacts with PTP1B and that the Nck/PTP1B complex inducibly associates with the IR for the attenuation of IR activation in mammalian cells. Our studies reveal for the first time that the adaptor protein Dock/Nck attenuates insulin signalling by recruiting PTP61F/PTP1B to its substrate, the IR.

  2. DOCK 8 Deficiency, EBV+ Lymphomatoid Granulomatosis, and Intrafamilial Variation in Presentation.

    Science.gov (United States)

    Dimitriades, Victoria R; Devlin, Vincent; Pittaluga, Stefania; Su, Helen C; Holland, Steven M; Wilson, Wyndham; Dunleavy, Kieron; Shah, Nirali N; Freeman, Alexandra F

    2017-01-01

    Dedicator of cytokinesis 8 (DOCK8) deficiency is an autosomal recessive, combined immunodeficiency within the spectrum of hyper-IgE syndromes. Epstein-Barr virus-positive lymphomatoid granulomatosis (LYG) (EBV + LYG) is a rare diagnosis and a previously unreported presentation of DOCK8 deficiency. A 10-year-old girl was initially evaluated for mild eczema and recurrent sinopulmonary infections. She had normal immunoglobulins with elevated IgE, poor polysaccharide response with low switched memory B cells, low CD4 count, and normal mitogen and antigen responses. Despite clinical improvement following immunoglobulin replacement, a prolonged cough prompted a CT scan, which showed nodules. Biopsy identified a Grade 2 EBV + LYG. Due to an inadequate response with chemotherapy, further workup for primary immunodeficiency was performed. With her symptoms of eczema and IgE elevation, along with her brother's history of recurrent sinopulmonary infections and warts, targeted sequencing of DOCK8 was performed revealing compound heterozygous mutations for the two siblings. Both patients were successfully transplanted with resolution of the LYG and warts, respectively. This is the first reported case of LYG in DOCK8 deficiency. The EBV-driven lymphoproliferative disease along with the infection history in the brother led to the diagnosis of DOCK8 deficiency and curative hematopoietic stem cell transplants.

  3. Occurrence of Potato virus X on hybrid dock in Czech Republic.

    Science.gov (United States)

    Petrzik, K

    2009-01-01

    Hybrid dock of Uteush (Rumex patientia L. x Rumex tianschanicus A. Los., the family Polygonaceae) is a perspective high productive crop and in the last decade its farming area has continuously grown in Czech Republic. However, the introduction of this non-native perennial crop into a present plant production creates a new potential reservoir for some plant viruses. Also, the hybrid dock could become a host of currently uncommon or insignificant viruses. We screened two dock-farming localities situated in south-west and north-east part of the Czech Republic for the presence of potyviruses, potexviruses, and carlaviruses. In the south-west part of the country, we detected a high incidence of Potato virus X (PVX, the genus Potexvirus). In contrast, in the north-east part of the country we did not detect any dock plants infected with PVX. Next, two other viruses, Turnip yellow mosaic virus (TYMV) and Radish mosaic virus (RaMV) were mechanically inoculated and tested for their survival capacity and multiplication in the hybrid dock. Both viruses were detected 9 months after inoculation in the infected plants.

  4. Genetic algorithm with a crossover elitist preservation mechanism for protein-ligand docking.

    Science.gov (United States)

    Guan, Boxin; Zhang, Changsheng; Ning, Jiaxu

    2017-09-13

    Protein-ligand docking plays an important role in computer-aided pharmaceutical development. Protein-ligand docking can be defined as a search algorithm with a scoring function, whose aim is to determine the conformation of the ligand and the receptor with the lowest energy. Hence, to improve an efficient algorithm has become a very significant challenge. In this paper, a novel search algorithm based on crossover elitist preservation mechanism (CEP) for solving protein-ligand docking problems is proposed. The proposed algorithm, namely genetic algorithm with crossover elitist preservation (CEPGA), employ the CEP to keep the elite individuals of the last generation and make the crossover more efficient and robust. The performance of CEPGA is tested on sixteen molecular docking complexes from RCSB protein data bank. In comparison with GA, LGA and SODOCK in the aspects of lowest energy and highest accuracy, the results of which indicate that the CEPGA is a reliable and successful method for protein-ligand docking problems.

  5. Energetic analysis of fragment docking and application to structure-based pharmacophore hypothesis generation

    Science.gov (United States)

    Loving, Kathryn; Salam, Noeris K.; Sherman, Woody

    2009-08-01

    We have developed a method that uses energetic analysis of structure-based fragment docking to elucidate key features for molecular recognition. This hybrid ligand- and structure-based methodology uses an atomic breakdown of the energy terms from the Glide XP scoring function to locate key pharmacophoric features from the docked fragments. First, we show that Glide accurately docks fragments, producing a root mean squared deviation (RMSD) of XP scoring function are mapped onto pharmacophore sites from the docked fragments in order to rank their importance for binding. Using this energetic analysis we show that the most energetically favorable pharmacophore sites are consistent with features from known tight binding compounds. Finally, we describe a method to use the energetically selected sites from fragment docking to develop a pharmacophore hypothesis that can be used in virtual database screening to retrieve diverse compounds. We find that this method produces viable hypotheses that are consistent with known active compounds. In addition to retrieving diverse compounds that are not biased by the co-crystallized ligand, the method is able to recover known active compounds from a database screen, with an average enrichment of 8.1 in the top 1% of the database.

  6. Effects of Low Earth Orbit on Docking Seal Materials

    Science.gov (United States)

    Imka, Emily C.; Asmar, Olivia C.; deGroh, Henry C., III; Banks, Bruce A.

    2014-01-01

    Spacecraft docking seals are typically made of silicone elastomers. When such seals are exposed to low Earth orbit (LEO) conditions, they can suffer damage from ultraviolet (UV) radiation and atomic oxygen (AO, or monoatomic oxygen, the predominant oxygen species in LEO). An experiment flew on the International Space Station (ISS) to measure the effects of LEO on seal materials S0383-70 and ELA-SA-401 and various mating counterface materials which included anodized aluminum. Samples flown in different orientations received different amounts of UV and AO. The hypotheses were that most of the damage would be from UV, and 10 days or more of exposure in LEO would badly damage the seals. Eighteen seals were exposed for 543 days in ram (windward), zenith (away from Earth), or wake (leeward) orientations, and 15 control samples (not flown) provided undamaged baseline leakage. To determine post-flight leak rates, each of the 33 seals were placed in an O-ring groove of a leak test fixture and pressure tested over time. Resistance temperature detectors (RTDs), pressure transducers, and LabVIEW (National Instruments) programs were used to measure and analyze the temperature and pressure and calculate leakage. Average leakage of control samples was 2.6 x 10(exp -7) lbs/day. LEO exposure did not considerably damage ELA-SA-401. The S0383-70 flight samples leaked at least 10 times more than ELA-SA-401 in all cases except one, demonstrating that ELA-SA-401 may be a more suitable sealing material in LEO. AO caused greater damage than UV; samples in ram orientation (receiving an AO fluence of 4.3 x 10(exp 21) atoms/(sq cm) and in wake (2.9x 10(exp 20) atoms/(sq cm)) leaked more than those in zenith orientation (1.58 x 10(exp 20) atoms/(sq cm)), whereas variations in UV exposure did not seem to affect the samples. Exposure to LEO did less damage to the seals than hypothesized, and the data did not support the conjecture that UV causes more damage than AO.

  7. Human and server docking prediction for CAPRI round 30-35 using LZerD with combined scoring functions.

    Science.gov (United States)

    Peterson, Lenna X; Kim, Hyungrae; Esquivel-Rodriguez, Juan; Roy, Amitava; Han, Xusi; Shin, Woong-Hee; Zhang, Jian; Terashi, Genki; Lee, Matt; Kihara, Daisuke

    2017-03-01

    We report the performance of protein-protein docking predictions by our group for recent rounds of the Critical Assessment of Prediction of Interactions (CAPRI), a community-wide assessment of state-of-the-art docking methods. Our prediction procedure uses a protein-protein docking program named LZerD developed in our group. LZerD represents a protein surface with 3D Zernike descriptors (3DZD), which are based on a mathematical series expansion of a 3D function. The appropriate soft representation of protein surface with 3DZD makes the method more tolerant to conformational change of proteins upon docking, which adds an advantage for unbound docking. Docking was guided by interface residue prediction performed with BindML and cons-PPISP as well as literature information when available. The generated docking models were ranked by a combination of scoring functions, including PRESCO, which evaluates the native-likeness of residues' spatial environments in structure models. First, we discuss the overall performance of our group in the CAPRI prediction rounds and investigate the reasons for unsuccessful cases. Then, we examine the performance of several knowledge-based scoring functions and their combinations for ranking docking models. It was found that the quality of a pool of docking models generated by LZerD, that is whether or not the pool includes near-native models, can be predicted by the correlation of multiple scores. Although the current analysis used docking models generated by LZerD, findings on scoring functions are expected to be universally applicable to other docking methods. Proteins 2017; 85:513-527. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. 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.

  9. Blinded evaluation of farnesoid X receptor (FXR) ligands binding using molecular docking and free energy calculations

    Science.gov (United States)

    Selwa, Edithe; Elisée, Eddy; Zavala, Agustin; Iorga, Bogdan I.

    2017-09-01

    Our participation to the D3R Grand Challenge 2 involved a protocol in two steps, with an initial analysis of the available structural data from the PDB allowing the selection of the most appropriate combination of docking software and scoring function. Subsequent docking calculations showed that the pose prediction can be carried out with a certain precision, but this is dependent on the specific nature of the ligands. The correct ranking of docking poses is still a problem and cannot be successful in the absence of good pose predictions. Our free energy calculations on two different subsets provided contrasted results, which might have the origin in non-optimal force field parameters associated with the sulfonamide chemical moiety.

  10. Protein-protein docking on hardware accelerators: comparison of GPU and MIC architectures

    Science.gov (United States)

    2015-01-01

    Background The hardware accelerators will provide solutions to computationally complex problems in bioinformatics fields. However, the effect of acceleration depends on the nature of the application, thus selection of an appropriate accelerator requires some consideration. Results In the present study, we compared the effects of acceleration using graphics processing unit (GPU) and many integrated core (MIC) on the speed of fast Fourier transform (FFT)-based protein-protein docking calculation. The GPU implementation performed the protein-protein docking calculations approximately five times faster than the MIC offload mode implementation. The MIC native mode implementation has the advantage in the implementation costs. However, the performance was worse with larger protein pairs because of memory limitations. Conclusion The results suggest that GPU is more suitable than MIC for accelerating FFT-based protein-protein docking applications. PMID:25707855

  11. Study on the interactions of trans-resveratrol and curcumin with bovine α-lactalbumin by spectroscopic analysis and molecular docking

    Energy Technology Data Exchange (ETDEWEB)

    Mohammadi, Fakhrossadat, E-mail: fmohammadi@iasbs.ac.ir; Moeeni, Marzieh

    2015-05-01

    The ability of bovine α-lactalbumin (BLA) as a whey protein to carry curcumin and trans-resveratrol as two natural polyphenolic compounds was investigated by fluorescence quenching measurements and docking studies. Curcumin is the bioactive component of turmeric and trans-resveratrol is abundant in different types of fruits and vegetables. The binding parameters such as binding constants and the number of substantive binding sites have been estimated from the analysis of fluorescence quenching measurements. The differences in affinities of curcumin and trans-resveratrol for BLA were compared. The short Förster's distance (r) between donor (BLA) and acceptor (curcumin and trans-resveratrol) and also the binding constant values demonstrated the strong interaction between these two polyphenolic compounds and BLA. The thermodynamic parameters were obtained from the fluorescence quenching measurements in different temperatures. It can be concluded from the sign and magnitude of ∆H and ∆S that the final ligand–protein complexes were stabilized by hydrogen bonds. The considerable change in microregion of the Trp residues in BLA is observed upon the binding of the trans-resveratrol to BLA by synchronous fluorescence while this conformation alteration was not observed upon interaction with curcumin. It was indicated by docking studies that curcumin come closer to the Trp-118 than to other tryptophans and trans-resveratrol binds in the vicinity of Trp-60 and Trp-104. Docking studies indicated that these two compounds bind to BLA by two hydrogen bonds. The calculated distances between bound ligands and tryptophans obtained by docking studies were in agreement with fluorescence resonance energy transfer results. Therefore, the strong interaction of curcumin and trans-resveratrol with BLA was confirmed by theoretical and experimental studies. These achieved results may be applicable in the milk industry and drug formulation. - Highlights: • The binding parameters

  12. Environmental and aesthetic impacts of small docks and piers, workshop report: Developing a science-based decision support tool for small dock management, phase 1: Status of the science

    OpenAIRE

    Kelty, Ruth; Bliven, Steve

    2003-01-01

    Few issues confronting coastal resource managers are as divisive or difficult to manage as regulating the construction of private recreational docks and piers associated with residential development. State resource managers face a growing population intent on living on or near the coast, coupled with an increasing desire to have immediate access to the water by private docks or piers. (PDF contains 69 pages)

  13. Evaluation of DOCK 6 as a pose generation and database enrichment tool.

    Science.gov (United States)

    Brozell, Scott R; Mukherjee, Sudipto; Balius, Trent E; Roe, Daniel R; Case, David A; Rizzo, Robert C

    2012-06-01

    In conjunction with the recent American Chemical Society symposium titled "Docking and Scoring: A Review of Docking Programs" the performance of the DOCK6 program was evaluated through (1) pose reproduction and (2) database enrichment calculations on a common set of organizer-specified systems and datasets (ASTEX, DUD, WOMBAT). Representative baseline grid score results averaged over five docking runs yield a relatively high pose identification success rate of 72.5 % (symmetry corrected rmsd) and sampling rate of 91.9 % for the multi site ASTEX set (N = 147) using organizer-supplied structures. Numerous additional docking experiments showed that ligand starting conditions, symmetry, multiple binding sites, clustering, and receptor preparation protocols all affect success. Encouragingly, in some cases, use of more sophisticated scoring and sampling methods yielded results which were comparable (Amber score ligand movable protocol) or exceeded (LMOD score) analogous baseline grid-score results. The analysis highlights the potential benefit and challenges associated with including receptor flexibility and indicates that different scoring functions have system dependent strengths and weaknesses. Enrichment studies with the DUD database prepared using the SB2010 preparation protocol and native ligand pairings yielded individual area under the curve (AUC) values derived from receiver operating characteristic curve analysis ranging from 0.29 (bad enrichment) to 0.96 (good enrichment) with an average value of 0.60 (27/38 have AUC ≥ 0.5). Strong early enrichment was also observed in the critically important 1.0-2.0 % region. Somewhat surprisingly, an alternative receptor preparation protocol yielded comparable results. As expected, semi-random pairings yielded poorer enrichments, in particular, for unrelated receptors. Overall, the breadth and number of experiments performed provide a useful snapshot of current capabilities of DOCK6 as well as starting points to

  14. 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

  15. The Drosophila DOCK family protein Sponge is required for development of the air sac primordium

    Energy Technology Data Exchange (ETDEWEB)

    Morishita, Kazushge; Anh Suong, Dang Ngoc; Yoshida, Hideki; Yamaguchi, Masamitsu, E-mail: myamaguc@kit.ac.jp

    2017-05-15

    Dedicator of cytokinesis (DOCK) family genes are known as DOCK1-DOCK11 in mammals. DOCK family proteins mainly regulate actin filament polymerization and/or depolymerization and are GEF proteins, which contribute to cellular signaling events by activating small G proteins. Sponge (Spg) is a Drosophila counterpart to mammalian DOCK3/DOCK4, and plays a role in embryonic central nervous system development, R7 photoreceptor cell differentiation, and adult thorax development. In order to conduct further functional analyses on Spg in vivo, we examined its localization in third instar larval wing imaginal discs. Immunostaining with purified anti-Spg IgG revealed that Spg mainly localized in the air sac primordium (ASP) in wing imaginal discs. Spg is therefore predicted to play an important role in the ASP. The specific knockdown of Spg by the breathless-GAL4 driver in tracheal cells induced lethality accompanied with a defect in ASP development and the induction of apoptosis. The monitoring of ERK signaling activity in wing imaginal discs by immunostaining with anti-diphospho-ERK IgG revealed reductions in the ERK signal cascade in Spg knockdown clones. Furthermore, the overexpression of D-raf suppressed defects in survival and the proliferation of cells in the ASP induced by the knockdown of Spg. Collectively, these results indicate that Spg plays a critical role in ASP development and tracheal cell viability that is mediated by the ERK signaling pathway. - Highlights: • Spg mainly localizes in the air sac primordium in wing imaginal discs. • Spg plays a critical role in air sac primordium development. • Spg positively regulates the ERK signal cascade.

  16. 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.

  17. 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.

  18. Spectroscopic and molecular docking studies on the interaction of antiviral drug nevirapine with calf thymus DNA.

    Science.gov (United States)

    Moghadam, Neda Hosseinpour; Salehzadeh, Sadegh; Shahabadi, Nahid

    2017-09-02

    The interaction of calf thymus DNA with nevirapine at physiological pH was studied by using absorption, circular dichroism, viscosity, differential pulse voltammetry, fluorescence techniques, salt effect studies and computational methods. The drug binds to ct-DNA in a groove binding mode, as shown by slight variation in the viscosity of ct-DNA. Furthermore, competitive fluorimetric studies with Hoechst 33258 indicate that nevirapine binds to DNA via groove binding. Moreover, the structure of nevirapine was optimized by DFT calculations and was used for the molecular docking calculations. The molecular docking results suggested that nevirapine prefers to bind on the minor groove of ct-DNA.

  19. Mining flexible-receptor docking experiments to select promising protein receptor snapshots.

    Science.gov (United States)

    Machado, Karina S; Winck, Ana T; Ruiz, Duncan D A; de Souza, Osmar Norberto

    2010-12-22

    Molecular docking simulation is the Rational Drug Design (RDD) step that investigates the affinity between protein receptors and ligands. Typically, molecular docking algorithms consider receptors as rigid bodies. Receptors are, however, intrinsically flexible in the cellular environment. The use of a time series of receptor conformations is an approach to explore its flexibility in molecular docking computer simulations, but it is extensively time-consuming. Hence, selection of the most promising conformations can accelerate docking experiments and, consequently, the RDD efforts. We previously docked four ligands (NADH, TCL, PIF and ETH) to 3,100 conformations of the InhA receptor from M. tuberculosis. Based on the receptor residues-ligand distances we preprocessed all docking results to generate appropriate input to mine data. Data preprocessing was done by calculating the shortest interatomic distances between the ligand and the receptor's residues for each docking result. They were the predictive attributes. The target attribute was the estimated free-energy of binding (FEB) value calculated by the AutodDock3.0.5 software. The mining inputs were submitted to the M5P model tree algorithm. It resulted in short and understandable trees. On the basis of the correlation values, for NADH, TCL and PIF we obtained more than 95% correlation while for ETH, only about 60%. Post processing the generated model trees for each of its linear models (LMs), we calculated the average FEB for their associated instances. From these values we considered a LM as representative if its average FEB was smaller than or equal the average FEB of the test set. The instances in the selected LMs were considered the most promising snapshots. It totalized 1,521, 1,780, 2,085 and 902 snapshots, for NADH, TCL, PIF and ETH respectively. By post processing the generated model trees we were able to propose a criterion of selection of linear models which, in turn, is capable of selecting a set of

  20. Insights into the biological functions of Dock family guanine nucleotide exchange factors.

    Science.gov (United States)

    Laurin, Mélanie; Côté, Jean-François

    2014-03-15

    Rho GTPases play key regulatory roles in many aspects of embryonic development, regulating processes such as differentiation, proliferation, morphogenesis, and migration. Two families of guanine nucleotide exchange factors (GEFs) found in metazoans, Dbl and Dock, are responsible for the spatiotemporal activation of Rac and Cdc42 proteins and their downstream signaling pathways. This review focuses on the emerging roles of the mammalian DOCK family in development and disease. We also discuss, when possible, how recent discoveries concerning the biological functions of these GEFs might be exploited for the development of novel therapeutic strategies.

  1. Pro-survival effect of Dock180 overexpression on rat-derived H9C2 cardiomyocytes.

    Science.gov (United States)

    Yan, An; Li, Gang; Zhang, Xu; Zhu, Bingbao; Linghu, Hua

    2013-01-14

    Integrin â1 subunit and its downstream molecule, focal adhesion kinase (FAK), have been demonstrated to be indispensible to the promotion of cell proliferation and survival and anti-apoptosis in cardiomyocytes via activation of their downstream pro-survival signaling molecule, AKT. As a component of the integrin pathway, Dock180 (dedicator of cytokinesis 1) protein is also thought to be involved in the promotion of cell proliferation and survival and anti-apoptosis in the H9C2 cardiomyocytes. Rat-derived H9C2 cardiomyocytes were transfected with pCXN2-flag-hDock180, a human Dock180 overexpression eukaryotic recombinant plasmid. The rat and human Dock180 mRNA and protein expression, apoptosis and cell proliferation and survival were analyzed in the H9C2 cardiomyocytes treated with either hypoxia/reoxygenation (H/R) or not, respectively. Human Dock180 mRNA overexpression could significantly increase the Dock180 protein expression in the H9C2 cardiomyocytes, no matter whether treated with H/R or not. Dock180 overexpression could promote the cell proliferation and survival and anti-apoptosis, and relieve the cell proliferative and survival inhibition and apoptosis induced by H/R in the H9C2 cardiomyocytes via activation of its downstream pro-survival signaling molecule AKT. Dock180 could act as a pro-survival molecule in H9C2 cardiomyocytes via activation of its downstream pro-survival signaling molecule, AKT.

  2. An Approach to Mathematical Modeling and Estimation of Probe-Drogue Docking Success Probability for UAV Autonomous Aerial Refueling

    Directory of Open Access Journals (Sweden)

    Xufeng Wang

    2017-01-01

    Full Text Available One of the keys to the success of aerial refueling for probe-drogue aerial refueling system (PDARS is the successful docking between the probe and drogue. The study of probe-drogue docking success probability offers an important support to achieving successful docking. During the docking phase of PDARS, based on prior information and reasonable assumptions for the movements of the drogue under atmospheric disturbance, the probe-drogue docking success probability is converted to the probability of the drogue center located in a specific area. A model of the probe-drogue docking success probability is established with and without actuation error, respectively. The curves of the probe-drogue docking success probability with the standard deviation of the drogue central position, the maximum distance from the drogue center position to the equilibrium position, the actuation error, and the standard deviation of the actuation error are obtained through simulations. The study has referential value for the docking maneuver decision of aerial refueling for PDARS.

  3. Methodology and problems of protein-ligand docking: case study of dihydroorotate dehydrogenase, thymidine kinase, and phosphodiesterase 4.

    Science.gov (United States)

    Pospisil, Pavel; Kuoni, Thomas; Scapozza, Leonardo; Folkers, Gerd

    2002-01-01

    The docking methodology was applied to three different therapeutically interesting enzymes: human dihydroorotate dehydrogenase (DHODH), Herpes simplex virus type I thymidine kinase (HSV1 TK) and human phosphodiesterase 4 (PDE4). Programs FlexX, AutoDock and DOCK where used. The three targets represent three distinct cases. For DHODH and HSV1 TK, the binding modes of substrate and inhibitors within the active site are known, while the binding orientation of cAMP within PDE4 has been solely hypothesized. Active site of DHODH is mainly hydrophobic and the binding mode of the inhibitor brequinar was used as a template for evaluating the docking strategies. The presence of cofactors revealed to be crucial for the definition of the docking site. The HSV1 TK active site is small and polar and contains crystal water molecules and ATP. Docking of thymidine and aciclovir (ACV) within the active site was analyzed by keeping or removing water molecules. It showed the crucial role of water in predicting the binding of pyrimidines and purines. The crystal structure of PDE4 contains magnesium and zinc cations as well as catalytic water molecule but no ligand. Several docking experiments of cAMP and rolipram were performed and the results showed clear-cut dependence between the ligand orientation and the presence of metals in the active site. All three cases show specific problems of the docking methodology, depending on the character of the active site.

  4. Docking and 3-D QSAR studies on the binding of tetrahydropyrimid-2-one HIV-1 protease inhibitors

    Science.gov (United States)

    Rao, Shashidhar N.; Balaji, Govardhan A.; Balaji, Vitukudi N.

    2013-06-01

    We present molecular docking and 3-D QSAR studies on a series of tetrahydropyrimid-2-one HIV-1 protease inhibitors whose binding affinities to the enzyme span nearly 6 orders of magnitude. The docking investigations have been carried out with Surflex (GEOM, GEOMX) and Glide (SP and XP) methodologies available through Tripos and Schrodinger suite of tools in the context of Sybyl-X and Maestro interfaces, respectively. The alignments for 3-D QSAR studies were obtained by using the automated Surflex-SIM methodology in Sybyl-X and the analyses were performed using the CoMFA and CoMSIA methods. Additionally, the top-ranked poses obtained from various docking protocols were also employed to generate CoMFA and CoMSIA models to evaluate the qualitative consistency of the docked models with experimental data. Our studies demonstrate that while there are a number of common features in the docked models obtained from Surflex-dock and Glide methodologies, the former sets of models are generally better correlated with deduced experimental binding modes based on the X-ray structures of known HIV-1 protease complexes with cyclic ureas. The urea moiety common to all the ligands are much more tightly aligned in Surflex docked structures than in the models obtained from Glide SP and XP dockings. The 3-D QSAR models are qualitatively and quantitatively similar to those previously reported, suggesting the utility of automatically generated alignments from Surflex-SIM methodology.

  5. Docking studies on DNA-ligand interactions: building and application of a protocol to identify the binding mode.

    Science.gov (United States)

    Ricci, Clarisse G; Netz, Paulo A

    2009-08-01

    Despite DNA being an important target for several drugs, most of the docking programs are validated only for proteins and their ligands. In this paper, we used AutoDock 4.0 to perform self-dockings and cross dockings between two DNA ligands (a minor groove binder and an intercalator) and four distinct receptors: 1) crystallographic DNA without intercalation gap; 2) crystallographic DNA with intercalation gap; 3) canonical B-DNA; and 4) modified B-DNA with intercalation gap. Besides being efficient in self-dockings, AutoDock is capable of correctly identifying two of the main DNA binding modes with the condition that the target possesses an artificial intercalation gap. Therefore, we suggest a default protocol to identify DNA binding modes which uses a modified canonical DNA (with gap) as receptor. This protocol was applied to dock two different Troger bases to DNA and the predicted binding modes agree with those suggested, yet not established, by experimental data. We also applied the protocol to dock aflatoxin B(1) exo-8,9-epoxide, and the results are in complete agreement with experimental data from the literature. We propose that this approach can be used to investigate other ligands whose binding mode to DNA remains unknown, yielding a suitable starting point for further theoretical studies such as molecular dynamics simulations.

  6. HDOCK: a web server for protein-protein and protein-DNA/RNA docking based on a hybrid strategy.

    Science.gov (United States)

    Yan, Yumeng; Zhang, Di; Zhou, Pei; Li, Botong; Huang, Sheng-You

    2017-05-17

    Protein-protein and protein-DNA/RNA interactions play a fundamental role in a variety of biological processes. Determining the complex structures of these interactions is valuable, in which molecular docking has played an important role. To automatically make use of the binding information from the PDB in docking, here we have presented HDOCK, a novel web server of our hybrid docking algorithm of template-based modeling and free docking, in which cases with misleading templates can be rescued by the free docking protocol. The server supports protein-protein and protein-DNA/RNA docking and accepts both sequence and structure inputs for proteins. The docking process is fast and consumes about 10-20 min for a docking run. Tested on the cases with weakly homologous complexes of server. The HDOCK web server is available at http://hdock.phys.hust.edu.cn/. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  7. The SKE-DOCK server and human teams based on a combined method of shape complementarity and free energy estimation.

    Science.gov (United States)

    Terashi, Genki; Takeda-Shitaka, Mayuko; Kanou, Kazuhiko; Iwadate, Mitsuo; Takaya, Daisuke; Umeyama, Hideaki

    2007-12-01

    We participated in rounds 6-12 of the critical assessment of predicted interaction (CAPRI) contest as the SKE-DOCK server and human teams. The SKE-DOCK server is based on simple geometry docking and a knowledge base scoring function. The procedure is summarized in the following three steps: (1) protein docking according to shape complementarity, (2) evaluating complex models, and (3) repacking side-chain of models. The SKE-DOCK server did not make use of biological information. On the other hand, the human team tried various intervention approaches. In this article, we describe in detail the processes of the SKE-DOCK server, together with results and reasons for success and failure. Good predicted models were obtained for target 25 by both the SKE-DOCK server and human teams. When the modeled receptor proteins were superimposed on the experimental structures, the smallest Ligand-rmsd values corresponding to the rmsd between the model and experimental structures were 3.307 and 3.324 A, respectively. Moreover, the two teams obtained 4 and 2 acceptable models for target 25. The overall result for both the SKE-DOCK server and human teams was medium accuracy for one (Target 25) out of nine targets. (c) 2007 Wiley-Liss, Inc.

  8. 18 CFR 1304.206 - Requirements for community docks, piers, boathouses, or other water-use facilities.

    Science.gov (United States)

    2010-04-01

    ... community docks, piers, boathouses, or other water-use facilities. 1304.206 Section 1304.206 Conservation of Power and Water Resources TENNESSEE VALLEY AUTHORITY APPROVAL OF CONSTRUCTION IN THE TENNESSEE RIVER....206 Requirements for community docks, piers, boathouses, or other water-use facilities. (a) Community...

  9. Application of fuzzy logic-neural network based reinforcement learning to proximity and docking operations: Special approach/docking testcase results

    Science.gov (United States)

    Jani, Yashvant

    1993-01-01

    As part of the RICIS project, the reinforcement learning techniques developed at Ames Research Center are being applied to proximity and docking operations using the Shuttle and Solar Maximum Mission (SMM) satellite simulation. In utilizing these fuzzy learning techniques, we use the Approximate Reasoning based Intelligent Control (ARIC) architecture, and so we use these two terms interchangeably to imply the same. This activity is carried out in the Software Technology Laboratory utilizing the Orbital Operations Simulator (OOS) and programming/testing support from other contractor personnel. This report is the final deliverable D4 in our milestones and project activity. It provides the test results for the special testcase of approach/docking scenario for the shuttle and SMM satellite. Based on our experience and analysis with the attitude and translational controllers, we have modified the basic configuration of the reinforcement learning algorithm in ARIC. The shuttle translational controller and its implementation in ARIC is described in our deliverable D3. In order to simulate the final approach and docking operations, we have set-up this special testcase as described in section 2. The ARIC performance results for these operations are discussed in section 3 and conclusions are provided in section 4 along with the summary for the project.

  10. Mechanism of porcine liver xanthine oxidoreductase mediated N-oxide reduction of cyadox as revealed by docking and mutagenesis studies.

    Directory of Open Access Journals (Sweden)

    Chigang Chen

    Full Text Available Xanthine oxidoreductase (XOR is a cytoplasmic molybdenum-containing oxidoreductase, catalyzing both endogenous purines and exogenous compounds. It is suggested that XOR in porcine hepatocytes catalyzes the N-oxide reduction of quinoxaline 1,4-di-N-oxides (QdNOs. To elucidate the molecular mechanism underlying this metabolism, the cDNA of porcine XOR was cloned and heterologously expressed in Spodoptera frugiperda insect cells. The bovine XOR, showing sequence identity of 91% to porcine XOR, was employed as template for homology modeling. By docking cyadox, a representative compound of QdNOs, into porcine XOR model, eight amino acid residues, Gly47, Asn352, Ser360, Arg427, Asp430, Asp431, Ser1227 and Lys1230, were located at distances of less than 4Å to cyadox. Site-directed mutagenesis was performed to analyze their catalytic functions. Compared with wild type porcine XOR, G47A, S360P, D431A, S1227A, and K1230A displayed altered kinetic parameters in cyadox reduction, similarly to that in xanthine oxidation, indicating these mutations influenced electron-donating process of xanthine before subsequent electron transfer to cyadox to fulfill the N-oxide reduction. Differently, R427E and D430H, both located in the 424-434 loop, exhibited a much lower K(m and a decreased V(max respectively in cyadox reduction. Arg427 may be related to the substrate binding of porcine XOR to cyadox, and Asp430 is suggested to be involved in the transfer of electron to cyadox. This study initially reveals the possible catalytic mechanism of porcine XOR in cyadox metabolism, providing with novel insights into the structure-function relationship of XOR in the reduction of exogenous di-N-oxides.

  11. Sulfonanilide Derivatives in Identifying Novel Aromatase Inhibitors by Applying Docking, Virtual Screening, and MD Simulations Studies

    Directory of Open Access Journals (Sweden)

    Shailima Rampogu

    2017-01-01

    Full Text Available Breast cancer is one of the leading causes of death noticed in women across the world. Of late the most successful treatments rendered are the use of aromatase inhibitors (AIs. In the current study, a two-way approach for the identification of novel leads has been adapted. 81 chemical compounds were assessed to understand their potentiality against aromatase along with the four known drugs. Docking was performed employing the CDOCKER protocol available on the Discovery Studio (DS v4.5. Exemestane has displayed a higher dock score among the known drug candidates and is labeled as reference. Out of 81 ligands 14 have exhibited higher dock scores than the reference. In the second approach, these 14 compounds were utilized for the generation of the pharmacophore. The validated four-featured pharmacophore was then allowed to screen Chembridge database and the potential Hits were obtained after subjecting them to Lipinski’s rule of five and the ADMET properties. Subsequently, the acquired 3,050 Hits were escalated to molecular docking utilizing GOLD v5.0. Finally, the obtained Hits were consequently represented to be ideal lead candidates that were escalated to the MD simulations and binding free energy calculations. Additionally, the gene-disease association was performed to delineate the associated disease caused by CYP19A1.

  12. Application of Numerical Optimization Methods to Perform Molecular Docking on Graphics Processing Units

    Directory of Open Access Journals (Sweden)

    M. A. Farkov

    2014-01-01

    Full Text Available An analysis of numerical optimization methods for solving a problem of molecular docking has been performed. Some additional requirements for optimization methods according to GPU architecture features were specified. A promising method for implementation on GPU was selected. Its implementation was described and performance and accuracy tests were performed.

  13. Drug targets for cell cycle dysregulators in leukemogenesis: in silico docking studies.

    Directory of Open Access Journals (Sweden)

    Archana Jayaraman

    Full Text Available Alterations in cell cycle regulating proteins are a key characteristic in neoplastic proliferation of lymphoblast cells in patients with Acute Lymphoblastic Leukemia (ALL. The aim of our study was to investigate whether the routinely administered ALL chemotherapeutic agents would be able to bind and inhibit the key deregulated cell cycle proteins such as--Cyclins E1, D1, D3, A1 and Cyclin Dependent Kinases (CDK 2 and 6. We used Schrödinger Glide docking protocol to dock the chemotherapeutic drugs such as Doxorubicin and Daunorubicin and others which are not very common including Clofarabine, Nelarabine and Flavopiridol, to the crystal structures of these proteins. We observed that the drugs were able to bind and interact with cyclins E1 and A1 and CDKs 2 and 6 while their docking to cyclins D1 and D3 were not successful. This binding proved favorable to interact with the G1/S cell cycle phase proteins that were examined in this study and may lead to the interruption of the growth of leukemic cells. Our observations therefore suggest that these drugs could be explored for use as inhibitors for these cell cycle proteins. Further, we have also highlighted residues which could be important in the designing of pharmacophores against these cell cycle proteins. This is the first report in understanding the mechanism of action of the drugs targeting these cell cycle proteins in leukemia through the visualization of drug-target binding and molecular docking using computational methods.

  14. Co-Operative Problem-Solving at the Royal Docks Community School

    Science.gov (United States)

    Martin, Ruth

    2013-01-01

    This article responds to Henry Tam's article in this issue of FORUM by exploring opportunities for co-operative problem-solving for staff and students of the Royal Docks Community School in the London Borough of Newham. Becoming a co-operative trust helped the school move out of special measures and develop a strategy of participation and…

  15. Advances in GPCR Modeling Evaluated by the GPCR Dock 2013 Assessment : Meeting New Challenges

    NARCIS (Netherlands)

    Kufareva, I.; Katritch, V.; Westen, van G.J.P.; Lenselink, E.B.; Overington, J.P.; Participants, of GPCR Dock 2013; Stevens, RC Abagyan R

    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

  16. Identification of novel bacterial histidine biosynthesis inhibitors using docking, ensemble rescoring, and whole-cell assays

    DEFF Research Database (Denmark)

    Henriksen, Signe Teuber; Liu, J.; Estiu, G.

    2010-01-01

    in the early stages of drug discovery attractive if sufficient accuracy can be achieved. Computational target identification using systems-level methods suggested the histidine biosynthesis pathway as an attractive target against S. aureus. Potential inhibitors for the pathway were identified through docking...

  17. Predicting the biological activities through QSAR analysis and docking-based scoring.

    Science.gov (United States)

    Vilar, Santiago; Costanzi, Stefano

    2012-01-01

    Numerous computational methodologies have been developed to facilitate the process of drug discovery. Broadly, they can be classified into ligand-based approaches, which are solely based on the calculation of the molecular properties of compounds, and structure-based approaches, which are based on the study of the interactions between compounds and their target proteins. This chapter deals with two major categories of ligand-based and structure-based methods for the prediction of biological activities of chemical compounds, namely quantitative structure-activity relationship (QSAR) analysis and docking-based scoring. QSAR methods are endowed with robustness and good ranking ability when applied to the prediction of the activity of closely related analogs; however, their great dependence on training sets significantly limits their applicability to the evaluation of diverse compounds. Instead, docking-based scoring, although not very effective in ranking active compounds on the basis of their affinities or potencies, offer the great advantage of not depending on training sets and have proven to be suitable tools for the distinction of active from inactive compounds, thus providing feasible platforms for virtual screening campaigns. Here, we describe the basic principles underlying the prediction of biological activities on the basis of QSAR and docking-based scoring, as well as a method to combine two or more individual predictions into a consensus model. Finally, we describe an example that illustrates the applicability of QSAR and molecular docking to G protein-coupled receptor (GPCR) projects.

  18. Simulation of a multi-agent system for autonomous trailer docking

    NARCIS (Netherlands)

    Gerrits, Berry; Mes, Martijn R.K.; Schuur, Peter

    2016-01-01

    This paper presents a simulation model of a generic automated planning and control system for the pick-up and docking of semi-trailers by means of autonomous Yard Tractors (YTs) in a collision- and con flict free environment. To support the planning and control of the YTs, we propose a Multi-Agent

  19. Implementation of Statistical Process Control: Evaluating the Mechanical Performance of a Candidate Silicone Elastomer Docking Seal

    Science.gov (United States)

    Oravec, Heather Ann; Daniels, Christopher C.

    2014-01-01

    The National Aeronautics and Space Administration has been developing a novel docking system to meet the requirements of future exploration missions to low-Earth orbit and beyond. A dynamic gas pressure seal is located at the main interface between the active and passive mating components of the new docking system. This seal is designed to operate in the harsh space environment, but is also to perform within strict loading requirements while maintaining an acceptable level of leak rate. In this study, a candidate silicone elastomer seal was designed, and multiple subscale test articles were manufactured for evaluation purposes. The force required to fully compress each test article at room temperature was quantified and found to be below the maximum allowable load for the docking system. However, a significant amount of scatter was observed in the test results. Due to the stochastic nature of the mechanical performance of this candidate docking seal, a statistical process control technique was implemented to isolate unusual compression behavior from typical mechanical performance. The results of this statistical analysis indicated a lack of process control, suggesting a variation in the manufacturing phase of the process. Further investigation revealed that changes in the manufacturing molding process had occurred which may have influenced the mechanical performance of the seal. This knowledge improves the chance of this and future space seals to satisfy or exceed design specifications.

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

    Indian Academy of Sciences (India)

    WINTEC

    Abstract. The interaction of pres1 region of hepatitis B virus B-cell epitope antigen with specific hepa- titis B neutralizing monoclonal antibody was examined by docking study. We modelled the 3D complex structure of B-cell epitope antigen residues CTTPAQGNSMFPSCCCTKPTDGNCY by homology model- ling and ...

  1. Numerical modeling of seawater flow through the flooding system of dry docks

    Directory of Open Access Journals (Sweden)

    A. Najafi-Jilani

    2009-12-01

    Full Text Available Numerical simulations have been carried out on the flooding system of a dry dock in design stage and to be located at the south coasts of Iran. The main goals of the present investigation are to evaluate the flooding time as well as the seawater flow characteristics in the intake channels of the dock. The time dependent upstream and downstream boundary conditions of the flooding system are imposed in the modeling. The upstream boundary condition is imposed in accordance with the tidal fluctuations of sea water level. At the downstream, the gradually rising water surface elevation in the dry dock is described in a transient boundary condition. The numerical results are compared with available laboratory measured data and a good agreement is obtained. The seawater discharge through the flooding system and the required time to filling up the dry dock is determined at the worst case. The water current velocity and pressure on the rigid boundaries are also calculated and discussed.

  2. Demonstration of Self-Training Autonomous Neural Networks in Space Vehicle Docking Simulations

    Science.gov (United States)

    Patrick, M. Clinton; Thaler, Stephen L.; Stevenson-Chavis, Katherine

    2006-01-01

    Neural Networks have been under examination for decades in many areas of research, with varying degrees of success and acceptance. Key goals of computer learning, rapid problem solution, and automatic adaptation have been elusive at best. This paper summarizes efforts at NASA's Marshall Space Flight Center harnessing such technology to autonomous space vehicle docking for the purpose of evaluating applicability to future missions.

  3. A Memetic Algorithm for the Vehicle Routing Problem with Cross Docking

    Directory of Open Access Journals (Sweden)

    Sanae Larioui

    2015-11-01

    Full Text Available In this paper we address the VRPCD, in which a set of homogeneous vehicles are used to transport products from the suppliers to customers via a cross-dock. The products can be consolidated at the cross-dock but cannot be stored for very long as the cross-dock does not have long-term inventory-holding capabilities. The objective of the VRPCD is to minimize the total traveled distance while respecting time window constraints of suppliers and customers and a time horizon for the whole transportation operation. Rummaging through all the work of literature on vehicle routing problems with cross-docking, there is no work that considers that customer will receive its requests from several suppliers; this will be the point of innovation of this work. A heuristic and a memetic algorithm are used to solve the problem. The proposed algorithms are implemented and tested on data sets involving up to 200 nodes (customers and suppliers. The first results show that the memetic algorithm can produce high quality solutions.

  4. What in silico molecular docking can do for the 'bench-working ...

    Indian Academy of Sciences (India)

    RB, FL http://www.biosolveit.de/FlexX/. Commercial program available for Linux and Windows, part of the LeadIT software solution. Good user interface. Takes account of the metal coordination. It allows the user to select which atoms of the ligand and the protein are able to be joined by a covalent bound. Dock 6 (Kuntz et al.

  5. Comparing an Approximate Queuing Approach with Simulation for the Solution of a Cross-Docking Problem

    Directory of Open Access Journals (Sweden)

    Roberta Briesemeister

    2017-01-01

    Full Text Available Cross-docking is a logistics management concept in which products are temporarily unloaded at intermediate facilities and loaded onto output trucks to be sent to their final destination. In this paper, we propose an approximate nonstationary queuing model to size the number of docks to receive the trucks, so that their unloading will be as short as possible at the receiving dock, thus making the cross-docking process more efficient. It is observed that the stochastic queuing process may not reach the steady equilibrium state. A type of modeling that does not depend on the stationary characteristics of the process developed is applied. In order to measure the efficiency, performance, and possible adjustments of the parameters of the algorithm, an alternative simulation model is proposed using the Arena® software. The simulation uses analytic tools to make the problem more detailed, which is not allowed in the theoretical model. The computational analysis compares the results of the simulated model with the ones obtained with the theoretical algorithm, considering the queue length and the average waiting time of the trucks. Based on the results obtained, the simulation represented very well the proposed problem and possible changes can be easily detected with small adjustments in the simulated model.

  6. Storing Fresh Produce for Fast Retrieval in an Automated Compact Cross-dock System

    NARCIS (Netherlands)

    Zaerpour, N.; Yu, Y.; de Koster, R.B.M.

    2015-01-01

    We study temporary storage of fresh produce in a cross-dock center. In order to minimize cooling cost, compact storage systems are used. A major disadvantage of these systems is that additional retrieval time is needed, caused by necessary reshuffles due to the improper storage sequence of unit

  7. Assessing protein-ligand docking for the binding of organometallic compounds to proteins.

    Science.gov (United States)

    Ortega-Carrasco, Elisabeth; Lledós, Agusti; Maréchal, Jean-Didier

    2014-01-30

    Organometallic compounds are increasingly used as molecular scaffolds in drug development projects; their structural and electronic properties offering novel opportunities in protein-ligand complementarities. Interestingly, while protein-ligand dockings have long become a spearhead in computer assisted drug design, no benchmarking nor optimization have been done for their use with organometallic compounds. Pursuing our efforts to model metal mediated recognition processes, we herein present a systematic study of the capabilities of the program GOLD to predict the interactions of protein with organometallic compounds. The study focuses on inert systems for which no alteration of the first coordination sphere of the metal occurs upon binding. Several scaffolds are used as test systems with different docking schemes and scoring functions. We conclude that ChemScore is the most robust scoring function with ASP and ChemPLP providing with good results too and GoldScore slightly underperforming. This study shows that current state-of-the-art protein-ligand docking techniques are reliable for the docking of inert organometallic compounds binding to protein. Copyright © 2013 Wiley Periodicals, Inc.

  8. The pepATTRACT web server for blind, large-scale peptide–protein docking

    Science.gov (United States)

    de Vries, Sjoerd J.; Rey, Julien; Schindler, Christina E. M.; Zacharias, Martin

    2017-01-01

    Abstract Peptide–protein interactions are ubiquitous in the cell and form an important part of the interactome. Computational docking methods can complement experimental characterization of these complexes, but current protocols are not applicable on the proteome scale. pepATTRACT is a novel docking protocol that is fully blind, i.e. it does not require any information about the binding site. In various stages of its development, pepATTRACT has participated in CAPRI, making successful predictions for five out of seven protein–peptide targets. Its performance is similar or better than state-of-the-art local docking protocols that do require binding site information. Here we present a novel web server that carries out the rigid-body stage of pepATTRACT. On the peptiDB benchmark, the web server generates a correct model in the top 50 in 34% of the cases. Compared to the full pepATTRACT protocol, this leads to some loss of performance, but the computation time is reduced from ∼18 h to ∼10 min. Combined with the fact that it is fully blind, this makes the web server well-suited for large-scale in silico protein–peptide docking experiments. The rigid-body pepATTRACT server is freely available at http://bioserv.rpbs.univ-paris-diderot.fr/services/pepATTRACT. PMID:28460116

  9. Modeling of a space flexible probe–cone docking system based on the Kane method

    Directory of Open Access Journals (Sweden)

    Zhang Xiang

    2014-04-01

    Full Text Available Recent developments in micro- and nano-satellites have attracted the interest of the research community worldwide. Many colleges and corporations have launched their satellites in space. Meanwhile, the space flexible probe–cone docking system for micro- and nano-satellites has become an attractive topic. In this paper, a dynamic model of a space flexible probe–cone docking system, in which the flexible beam technology is applied, is built based on the Kane method. The curves of impact force versus time are obtained by the Lagrange model, the Kane model, and the experimental method. The Lagrange model was presented in the reference and verified by both finite element simulation and experiment. The results of the three methods show good agreements on the condition that the beam flexibility and the initial relative velocity change. It is worth mentioning that the introduction of vectorial mechanics and analytical mechanics in the Kane method leads to a large reduction of differential operations and makes the modeling process much easier than that of the Lagrange method. Moreover, the influences of the beam flexibility and the initial relative velocity are discussed. It is concluded that the initial relative velocity of space docking operation should be controlled to a certain value in order to protect the docking system.

  10. QUERCETIN DERIVATIVES DOCKING BASED ON STUDY OF FLAVONOIDS INTERACTION TO CYCLOOXYGENASE-2

    Directory of Open Access Journals (Sweden)

    Rahmana Emran Kartasasmita

    2010-06-01

    Full Text Available Due to their ability to inhibit cyclooxygenase-2 (COX-2, certain flavonoids show anti-inflammatory effects. Quercetin is a flavonoid suitable to be chosen as the lead compound for development of safe anti-inflammatory agent, because in addition to its anti-inflammatory effect, quercetin shows also protective effect in gastrointestinal track. The objective of this research is to study the binding modes of certain flavonoids and predict the quercetin derivatives inhibiton activity on COX-2 by means of docking method using ArgusLab 4.0.1 software. Some flavonoids (7-hydroxyflavone, apigenin, galangin, kaempferol, quercetin, naringenin and daidzein and quercetin derivatives were used as ligands for docking study. The COX-2 structure was obtained from Brookhaven protein databank. After assigning hydrogen atoms and charges, computational docking was performed. The docking results were evaluated based on the binding energy and hydrogen bonding of  the ligands on binding site of COX-2. A curve constructed by plotting binding energy versus logarithm of IC50 of flavonoids shows a good correlation with a regression equation of log IC50 = 0.8069 ΔGbind + 9.4456 (r = 0.9226; P

  11. 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...

  12. High-throughput Molecular Docking Now in Reach for a Wider Biochemical Community

    NARCIS (Netherlands)

    Balan, D.M.; Malinauskas, T.; Prins, J.C.P.; Moller, S.

    2012-01-01

    In silico molecular docking is used to predict how a small molecule, the ligand, interacts with a target protein, its receptor. Together with experimental methods like NMR or X-ray crystallography, industrial and academic groups use it for their investigation of compounds with the potential to

  13. 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.

  14. An Insight into the Anticancer Activities of Ru(II-Based Metallocompounds Using Docking Methods

    Directory of Open Access Journals (Sweden)

    Peter A. Ajibade

    2013-09-01

    Full Text Available Unlike organic molecules, reports on docking of metal complexes are very few; mainly due to the inadequacy of force fields in docking packages to appropriately characterize the metal atoms that consequentially hinder the rational design of metal-based drug complexes. In this study we have made used Molegro and Autodock to predict the anticancer activities of selected Ru(II complexes against twelve anticancer targets. We observed that introducing the quantum calculated atomic charges of the optimized geometries significantly improved the docking predictions of these anticancer metallocompounds. Despite several limitations in the docking of metal-based complexes, we obtained results that are highly correlated with the available experimental results. Most of our newly proposed metallocompounds are found theoretically to be better anticancer metallocompounds than all the experimentally proposed RAPTA complexes. An interesting features of a strong interactions of new modeled of metallocompounds against the two base edges of DNA strands suggest similar mechanisms of anticancer activities similar to that of cisplatin. There is possibility of covalent bonding between the metal center of the metallocompounds and the residues of the receptors DNA-1, DNA-2, HDAC7, HIS and RNR. However, the general results suggest the possibility of metals positioning the coordinated ligands in the right position for optimal receptor interactions and synergistic effects, rather than forming covalent bonds.

  15. Accounting for conformational variability in protein-ligand docking with NMR-guided rescoring.

    Science.gov (United States)

    Skjærven, Lars; Codutti, Luca; Angelini, Andrea; Grimaldi, Manuela; Latek, Dorota; Monecke, Peter; Dreyer, Matthias K; Carlomagno, Teresa

    2013-04-17

    A key component to success in structure-based drug design is reliable information on protein-ligand interactions. Recent development in NMR techniques has accelerated this process by overcoming some of the limitations of X-ray crystallography and computational protein-ligand docking. In this work we present a new scoring protocol based on NMR-derived interligand INPHARMA NOEs to guide the selection of computationally generated docking modes. We demonstrate the performance in a range of scenarios, encompassing traditionally difficult cases such as docking to homology models and ligand dependent domain rearrangements. Ambiguities associated with sparse experimental information are lifted by searching a consensus solution based on simultaneously fitting multiple ligand pairs. This study provides a previously unexplored integration between molecular modeling and experimental data, in which interligand NOEs represent the key element in the rescoring algorithm. The presented protocol should be widely applicable for protein-ligand docking also in a different context from drug design and highlights the important role of NMR-based approaches to describe intermolecular ligand-receptor interactions.

  16. What in silico molecular docking can do for the 'bench-working ...

    Indian Academy of Sciences (India)

    Required by an increasing amount of scientists, the in silico docking field is in full expansion, new algorithms and methods appearing at an exponential rate. The sheer range of available programs is overwhelming for the bench-working biologist, which is often discouraging by the lack of a graphical user interface, good ...

  17. The pepATTRACT web server for blind, large-scale peptide-protein docking.

    Science.gov (United States)

    de Vries, Sjoerd J; Rey, Julien; Schindler, Christina E M; Zacharias, Martin; Tuffery, Pierre

    2017-04-29

    Peptide-protein interactions are ubiquitous in the cell and form an important part of the interactome. Computational docking methods can complement experimental characterization of these complexes, but current protocols are not applicable on the proteome scale. pepATTRACT is a novel docking protocol that is fully blind, i.e. it does not require any information about the binding site. In various stages of its development, pepATTRACT has participated in CAPRI, making successful predictions for five out of seven protein-peptide targets. Its performance is similar or better than state-of-the-art local docking protocols that do require binding site information. Here we present a novel web server that carries out the rigid-body stage of pepATTRACT. On the peptiDB benchmark, the web server generates a correct model in the top 50 in 34% of the cases. Compared to the full pepATTRACT protocol, this leads to some loss of performance, but the computation time is reduced from ∼18 h to ∼10 min. Combined with the fact that it is fully blind, this makes the web server well-suited for large-scale in silico protein-peptide docking experiments. The rigid-body pepATTRACT server is freely available at http://bioserv.rpbs.univ-paris-diderot.fr/services/pepATTRACT. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. Meta-server for automatic analysis, scoring and ranking of docking models.

    Science.gov (United States)

    Anashkina, Anastasia A; Kravatsky, Yuri; Kuznetsov, Eugene; Makarov, Alexander A; Adzhubei, Alexei A

    2017-09-18

    Modelling with multiple servers that use different algorithms for docking results in more reliable predictions of interaction sites. However, the scoring and comparison of all models by an expert is time-consuming and is not feasible for large volumes of data generated by such modelling. QASDOM Server (Quality ASsessment of DOcking Models) is a simple and efficient tool for real-time simultaneous analysis, scoring and ranking of datasets of receptor-ligand complexes built by a range of docking techniques. This meta-server is designed to analyse large datasets of docking models and rank them by scoring criteria developed in this study. It produces two types of output showing the likelihood of specific residues and clusters of residues to be involved in receptor-ligand interactions, and the ranking of models. The server also allows visualising residues that form interaction sites in the receptor and ligand sequence, and displays three-dimensional model structures of the receptor-ligand complexes. http://qasdom.eimb.ru. Supplementary data are available at Bioinformatics online.

  19. An Experimental Investigation of Leak Rate Performance of a Subscale Candidate Elastomer Docking Space Seal

    Science.gov (United States)

    Garafolo, Nicholas G.; Daniels, Christopher C.

    2011-01-01

    A novel docking seal was developed for the main interface seal of NASA s Low Impact Docking System (LIDS). This interface seal was designed to maintain acceptable leak rates while being exposed to the harsh environmental conditions of outer space. In this experimental evaluation, a candidate docking seal assembly called Engineering Development Unit (EDU58) was characterized and evaluated against the Constellation Project leak rate requirement. The EDU58 candidate seal assembly was manufactured from silicone elastomer S0383-70 vacuum molded in a metal retainer ring. Four seal designs were considered with unique characteristic heights. The leak rate performance was characterized through a mass point leak rate method by monitoring gas properties within an internal control volume. The leakage performance of the seals were described herein at representative docking temperatures of -50, +23, and +50 C for all four seal designs. Leak performance was also characterized at 100, 74, and 48 percent of full closure. For all conditions considered, the candidate seal assemblies met the Constellation Project leak rate requirement.

  20. DOCKING OF STRUCTURALLY RELATED DIOLEPOXIDES OF BENZO(GHI)FLUORANTHENE WITH DNA

    Science.gov (United States)

    Docking of structurally-related diolepoxides of benzo{ghi}fluoranthene and benzo{c}phenanthrene with DNAPolycyclic aromatic hydrocarbons are a class of chemicals found in the environment. Some class members are potent carcinogens while others with similar structures show litt...

  1. Activated Cdc42 kinase regulates Dock localization in male germ cells during Drosophila spermatogenesis.

    Science.gov (United States)

    Abdallah, Abbas M; Zhou, Xin; Kim, Christine; Shah, Kushani K; Hogden, Christopher; Schoenherr, Jessica A; Clemens, James C; Chang, Henry C

    2013-06-15

    Deregulation of the non-receptor tyrosine kinase ACK1 (Activated Cdc42-associated kinase) correlates with poor prognosis in cancers and has been implicated in promoting metastasis. To further understand its in vivo function, we have characterized the developmental defects of a null mutation in Drosophila Ack, which bears a high degree of sequence similarity to mammalian ACK1 but lacks a CRIB domain. We show that Ack, while not essential for viability, is critical for sperm formation. This function depends on Ack tyrosine kinase activity and is required cell autonomously in differentiating male germ cells at or after the spermatocyte stage. Ack associates predominantly with endocytic clathrin sites in spermatocytes, but disruption of Ack function has no apparent effect on clathrin localization and receptor-mediated internalization of Boss (Bride of sevenless) protein in eye discs. Instead, Ack is required for the subcellular distribution of Dock (dreadlocks), the Drosophila homolog of the SH2- and SH3-containing adaptor protein Nck. Moreover, Dock forms a complex with Ack, and the localization of Dock in male germ cells depends on its SH2 domain. Together, our results suggest that Ack-dependent tyrosine phosphorylation recruits Dock to promote sperm differentiation. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. A robot to detect and control broad-leaved dock (Rumex obtusifolius L.) in grassland

    NARCIS (Netherlands)

    Evert, van F.K.; Samsom, J.; Polder, G.; Vijn, M.P.; Dooren, van H.J.C.; Lamaker, E.J.J.; Heijden, van der G.W.A.M.; Kempenaar, C.; Zalm, van der A.J.A.; Lotz, L.A.P.

    2011-01-01

    Broad-leaved dock is a common and troublesome grassland weed with a wide geographic distribution. In conventional farming the weed is normally controlled by using a selective herbicide, but in organic farming manual removal is the best option to control this weed. The objective of our work was to

  3. Drosophila DOCK family protein sponge regulates the JNK pathway during thorax development.

    Science.gov (United States)

    Morishita, Kazushige; Ozasa, Fumito; Eguchi, Koichi; Yoshioka, Yasuhide; Yoshida, Hideki; Hiai, Hiroshi; Yamaguchi, Masamitsu

    2014-01-01

    The dedicator of cytokinesis (DOCK) family proteins that are conserved in a wide variety of species are known as DOCK1-DOCK11 in mammals. The Sponge (Spg) is a Drosophila counterpart to the mammalian DOCK3. Specific knockdown of spg by pannir-GAL4 or apterous-GAL4 driver in wing discs induced split thorax phenotype in adults. Reduction of the Drosophila c-Jun N-terminal kinase (JNK), basket (bsk) gene dose enhanced the spg knockdown-induced phenotype. Conversely, overexpression of bsk suppressed the split thorax phenotype. Monitoring JNK activity in the wing imaginal discs by immunostaining with anti-phosphorylated JNK (anti-pJNK) antibody together with examination of lacZ expression in a puckered-lacZ enhancer trap line revealed the strong reduction of the JNK activity in the spg knockdown clones. This was further confirmed by Western immunoblot analysis of extracts from wing discs of spg knockdown fly with anti-pJNK antibody. Furthermore, the Duolink in situ Proximity Ligation Assay method detected interaction signals between Spg and Rac1 in the wing discs. Taken together, these results indicate Spg positively regulates JNK pathway that is required for thorax development and the regulation is mediated by interaction with Rac1.

  4. Identification of Novel Aldose Reductase Inhibitors from Spices: A Molecular Docking and Simulation Study.

    Directory of Open Access Journals (Sweden)

    Priya Antony

    Full Text Available Hyperglycemia in diabetic patients results in a diverse range of complications such as diabetic retinopathy, neuropathy, nephropathy and cardiovascular diseases. The role of aldose reductase (AR, the key enzyme in the polyol pathway, in these complications is well established. Due to notable side-effects of several drugs, phytochemicals as an alternative has gained considerable importance for the treatment of several ailments. In order to evaluate the inhibitory effects of dietary spices on AR, a collection of phytochemicals were identified from Zingiber officinale (ginger, Curcuma longa (turmeric Allium sativum (garlic and Trigonella foenum graecum (fenugreek. Molecular docking was performed for lead identification and molecular dynamics simulations were performed to study the dynamic behaviour of these protein-ligand interactions. Gingerenones A, B and C, lariciresinol, quercetin and calebin A from these spices exhibited high docking score, binding affinity and sustained protein-ligand interactions. Rescoring of protein ligand interactions at the end of MD simulations produced binding scores that were better than the initially docked conformations. Docking results, ligand interactions and ADMET properties of these molecules were significantly better than commercially available AR inhibitors like epalrestat, sorbinil and ranirestat. Thus, these natural molecules could be potent AR inhibitors.

  5. Challenges, Applications, and Recent Advances of Protein-Ligand Docking in Structure-Based Drug Design

    Directory of Open Access Journals (Sweden)

    Sam Z. Grinter

    2014-07-01

    Full Text Available The docking methods used in structure-based virtual database screening offer the ability to quickly and cheaply estimate the affinity and binding mode of a ligand for the protein receptor of interest, such as a drug target. These methods can be used to enrich a database of compounds, so that more compounds that are subsequently experimentally tested are found to be pharmaceutically interesting. In addition, like all virtual screening methods used for drug design, structure-based virtual screening can focus on curated libraries of synthesizable compounds, helping to reduce the expense of subsequent experimental verification. In this review, we introduce the protein-ligand docking methods used for structure-based drug design and other biological applications. We discuss the fundamental challenges facing these methods and some of the current methodological topics of interest. We also discuss the main approaches for applying protein-ligand docking methods. We end with a discussion of the challenging aspects of evaluating or benchmarking the accuracy of docking methods for their improvement, and discuss future directions.

  6. 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…

  7. 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.

  8. Functional analysis of the binding model of microbial inulinases using docking and molecular dynamics simulation.

    Science.gov (United States)

    Singh, Puneet Kumar; Joseph, Josmi; Goyal, Sukriti; Grover, Abhinav; Shukla, Pratyoosh

    2016-04-01

    Recently inulinase has regained interest due to its usage in the production of fructooligosaccharides, biofuels, and in pharmaceutical industries. Inulinases properties are experimentally reported by nomerous studies but their characteristics are just partially explained by only a few computational investigations. In the present study we have investigated exoinulinase and endoinulinase from different microbial sources toward their catalytic activity. Docking and molecular dynamic (MD) simulation were carried out for microbial endoinulinase and exoinulinase docked with 1-kestose and fructose-6-phosphate respectively. Pseudomonas mucidolens (-7.42 kcal mol(-1) binding energy), docked with fructose-6-phosphate, was recorded as the most favorable binding energy, Pseudomonas mucidolens made hydrogen bonds with fructose-6-phosphate and the amino acids involved were arginine 286, tryptophan 158, and isoleucine 87. After the simulation only tryptophan 158 remained bonded and additionally valine 156 made hydrogen bonds with fructose-6-phosphate. Aspergillus niger docked with 1-kestose was bonded with the involvement of threonine 271, aspartate 285, threonine 288, and proline 283, after the simulation aspartate 285 was retained till the end of the simulation. The present study thus refers to the indication of depicting binding analysis of microbial inulinases.

  9. Docking of LDCVs is modulated by lower intracellular [Ca2+] than priming.

    Directory of Open Access Journals (Sweden)

    Mathias Pasche

    Full Text Available Many regulatory steps precede final membrane fusion in neuroendocrine cells. Some parts of this preparatory cascade, including fusion and priming, are dependent on the intracellular Ca(2+ concentration ([Ca(2+](i. However, the functional implications of [Ca(2+](i in the regulation of docking remain elusive and controversial due to an inability to determine the modulatory effect of [Ca(2+](i. Using a combination of TIRF-microscopy and electrophysiology we followed the movement of large dense core vesicles (LDCVs close to the plasma membrane, simultaneously measuring membrane capacitance and [Ca(2+](i. We found that a free [Ca(2+](i of 700 nM maximized the immediately releasable pool and minimized the lateral mobility of vesicles, which is consistent with a maximal increase of the pool size of primed LDCVs. The parameters that reflect docking, i.e. axial mobility and the fraction of LDCVs residing at the plasma membrane for less than 5 seconds, were strongly decreased at a free [Ca(2+](i of 500 nM. These results provide the first evidence that docking and priming occur at different free intracellular Ca(2+ concentrations, with docking efficiency being the most robust at 500 nM.

  10. [Screening of anti-aging active ingredients and mechanism analysis based on molecular docking technology].

    Science.gov (United States)

    Du, Ran-Feng; Zhang, Xiao-Hua; Ye, Xiao-Tong; Yu, Wen-Kang; Wang, Yun

    2016-07-01

    Dampness evil is the source of all diseases, which is easy to cause disease and promote aging, while aging could also promote the occurence and development of diseases. In this paper, the relationship between the dampness evil and aging would be discussed, to find the anti-aging active ingredients in traditional Chinese medicine (TCM), and analyze the anti-aging mechanism of dampness eliminating drug. Molecular docking technology was used, with aging-related mammalian target of rapamycin as the docking receptors, and chemical components of Fuling, Sangzhi, Mugua, Yiyiren and Houpo as the docking molecules, to preliminarily screen the anti-aging active ingredients in dampness eliminating drug. Through the comparison with active drugs already on the market (temsirolimus and everolimus), 12 kinds of potential anti-aging active ingredients were found, but their drug gability still needs further study. The docking results showed that various components in the dampness eliminating drug can play anti-aging activities by acting on mammalian target of rapamycin. This result provides a new thought and direction for the method of delaying aging by eliminating dampness. Copyright© by the Chinese Pharmaceutical Association.

  11. Increased expression of Dock180 protein in the noninfarcted myocardium in rats.

    Science.gov (United States)

    Liu, Xiao-Lan; Li, Gang; Wang, Zhi-Hua; Zhao, Wen-Ju; Wang, Li-Ping

    2013-03-01

    The integrin β1 subunit and its downstream molecule focal adhesion kinase have been identified as critical molecules for the inhibition of postinfarction cardiac remodeling, ischemic cardiomyopathy, and heart failure. However, as a component of the integrin pathway, it is still unclear whether Dock180 (dedicator of cytokinesis 1) protein is expressed in the noninfarcted myocardium of the peri-infarct zones. In this study, experimental myocardial infarction (MI) and sham-operation (sham) models were established in Sprague Dawley rats and the expression of Dock180 protein in the myocardium of the sham group and in the noninfarcted myocardium of the peri-infarct zones of the MI group was detected by Western blot technique. The Dock180 protein expression in the myocardium was as follows: postsham 24-hour group, 0.10 ± 0.04 (n = 8); post-MI 24-hour group, 0.13 ± 0.03 (n = 8); postsham 12-week group, 0.11 ± 0.05 (n = 8); and post-MI 12-week group 0.17 ± 0.04 (n = 8). The Dock180 protein expression in the myocardium in the post-MI 12-week group was significantly higher than that in the postsham 12-week group (p = 0.019), in the postsham 24-hour group (p = 0.004), and in the post-MI 24-hour group (p = 0.040). We conclude that Dock180 protein is expressed in the myocardium in rats. Furthermore, its expression is significantly increased in the noninfarcted myocardium of the peri-infarct zones. Copyright © 2012. Published by Elsevier B.V.

  12. Protein-DNA docking with a coarse-grained force field

    Directory of Open Access Journals (Sweden)

    Setny Piotr

    2012-09-01

    Full Text Available Abstract Background Protein-DNA interactions are important for many cellular processes, however structural knowledge for a large fraction of known and putative complexes is still lacking. Computational docking methods aim at the prediction of complex architecture given detailed structures of its constituents. They are becoming an increasingly important tool in the field of macromolecular assemblies, complementing particularly demanding protein-nucleic acids X ray crystallography and providing means for the refinement and integration of low resolution data coming from rapidly advancing methods such as cryoelectron microscopy. Results We present a new coarse-grained force field suitable for protein-DNA docking. The force field is an extension of previously developed parameter sets for protein-RNA and protein-protein interactions. The docking is based on potential energy minimization in translational and orientational degrees of freedom of the binding partners. It allows for fast and efficient systematic search for native-like complex geometry without any prior knowledge regarding binding site location. Conclusions We find that the force field gives very good results for bound docking. The quality of predictions in the case of unbound docking varies, depending on the level of structural deviation from bound geometries. We analyze the role of specific protein-DNA interactions on force field performance, both with respect to complex structure prediction, and the reproduction of experimental binding affinities. We find that such direct, specific interactions only partially contribute to protein-DNA recognition, indicating an important role of shape complementarity and sequence-dependent DNA internal energy, in line with the concept of indirect protein-DNA readout mechanism.

  13. Assessment of Spatial Navigation and Docking Performance During Simulated Rover Tasks

    Science.gov (United States)

    Wood, S. J.; Dean, S. L.; De Dios, Y. E.; Moore, S. T.

    2010-01-01

    INTRODUCTION: Following long-duration exploration transits, pressurized rovers will enhance surface mobility to explore multiple sites across Mars and other planetary bodies. Multiple rovers with docking capabilities are envisioned to expand the range of exploration. However, adaptive changes in sensorimotor and cognitive function may impair the crew s ability to safely navigate and perform docking tasks shortly after transition to the new gravitoinertial environment. The primary goal of this investigation is to quantify post-flight decrements in spatial navigation and docking performance during a rover simulation. METHODS: Eight crewmembers returning from the International Space Station will be tested on a motion simulator during four pre-flight and three post-flight sessions over the first 8 days following landing. The rover simulation consists of a serial presentation of discrete tasks to be completed within a scheduled 10 min block. The tasks are based on navigating around a Martian outpost spread over a 970 sq m terrain. Each task is subdivided into three components to be performed as quickly and accurately as possible: (1) Perspective taking: Subjects use a joystick to indicate direction of target after presentation of a map detailing current orientation and location of the rover with the task to be performed. (2) Navigation: Subjects drive the rover to the desired location while avoiding obstacles. (3) Docking: Fine positioning of the rover is required to dock with another object or align a camera view. Overall operator proficiency will be based on how many tasks the crewmember can complete during the 10 min time block. EXPECTED RESULTS: Functionally relevant testing early post-flight will develop evidence regarding the limitations to early surface operations and what countermeasures are needed. This approach can be easily adapted to a wide variety of simulated vehicle designs to provide sensorimotor assessments for other operational and civilian populations.

  14. 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.

  15. Ensemble pharmacophore meets ensemble docking: a novel screening strategy for the identification of RIPK1 inhibitors.

    Science.gov (United States)

    Fayaz, S M; Rajanikant, G K

    2014-07-01

    Programmed cell death has been a fascinating area of research since it throws new challenges and questions in spite of the tremendous ongoing research in this field. Recently, necroptosis, a programmed form of necrotic cell death, has been implicated in many diseases including neurological disorders. Receptor interacting serine/threonine protein kinase 1 (RIPK1) is an important regulatory protein involved in the necroptosis and inhibition of this protein is essential to stop necroptotic process and eventually cell death. Current structure-based virtual screening methods involve a wide range of strategies and recently, considering the multiple protein structures for pharmacophore extraction has been emphasized as a way to improve the outcome. However, using the pharmacophoric information completely during docking is very important. Further, in such methods, using the appropriate protein structures for docking is desirable. If not, potential compound hits, obtained through pharmacophore-based screening, may not have correct ranks and scores after docking. Therefore, a comprehensive integration of different ensemble methods is essential, which may provide better virtual screening results. In this study, dual ensemble screening, a novel computational strategy was used to identify diverse and potent inhibitors against RIPK1. All the pharmacophore features present in the binding site were captured using both the apo and holo protein structures and an ensemble pharmacophore was built by combining these features. This ensemble pharmacophore was employed in pharmacophore-based screening of ZINC database. The compound hits, thus obtained, were subjected to ensemble docking. The leads acquired through docking were further validated through feature evaluation and molecular dynamics simulation.

  16. Extra precision docking, free energy calculation and molecular dynamics studies on glutamic acid derivatives as MurD inhibitors.

    Science.gov (United States)

    Azam, Mohammed Afzal; Jupudi, Srikanth

    2017-08-01

    The binding modes of well known MurD inhibitors have been studied using molecular docking and molecular dynamics (MD) simulations. The docking results of inhibitors 1-30 revealed similar mode of interaction with Escherichia coli-MurD. Further, residues Thr36, Arg37, His183, Lys319, Lys348, Thr321, Ser415 and Phe422 are found to be important for inhibitors and E. coli-MurD interactions. Our docking procedure precisely predicted crystallographic bound inhibitor 7 as evident from root mean square deviation (0.96Å). In addition inhibitors 2 and 3 have been successfully cross-docked within the MurD active site, which was pre-organized for the inhibitor 7. Induced fit best docked poses of 2, 3, 7 and 15/2Y1O complexes were subjected to 10ns MD simulations to determine the stability of the predicted binding conformations. Induce fit derived docked complexes were found to be in a state of near equilibrium as evident by the low root mean square deviations between the starting complex structure and the energy minimized final average MD complex structures. The results of molecular docking and MD simulations described in this study will be useful for the development of new MurD inhibitors with high potency. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Fragment-based docking: development of the CHARMMing Web user interface as a platform for computer-aided drug design.

    Science.gov (United States)

    Pevzner, Yuri; Frugier, Emilie; Schalk, Vinushka; Caflisch, Amedeo; Woodcock, H Lee

    2014-09-22

    Web-based user interfaces to scientific applications are important tools that allow researchers to utilize a broad range of software packages with just an Internet connection and a browser. One such interface, CHARMMing (CHARMM interface and graphics), facilitates access to the powerful and widely used molecular software package CHARMM. CHARMMing incorporates tasks such as molecular structure analysis, dynamics, multiscale modeling, and other techniques commonly used by computational life scientists. We have extended CHARMMing's capabilities to include a fragment-based docking protocol that allows users to perform molecular docking and virtual screening calculations either directly via the CHARMMing Web server or on computing resources using the self-contained job scripts generated via the Web interface. The docking protocol was evaluated by performing a series of "re-dockings" with direct comparison to top commercial docking software. Results of this evaluation showed that CHARMMing's docking implementation is comparable to many widely used software packages and validates the use of the new CHARMM generalized force field for docking and virtual screening.

  18. FReDoWS: a method to automate molecular docking simulations with explicit receptor flexibility and snapshots selection.

    Science.gov (United States)

    Machado, Karina S; Schroeder, Evelyn K; Ruiz, Duncan D; Cohen, Elisângela M L; de Souza, Osmar Norberto

    2011-12-22

    In silico molecular docking is an essential step in modern drug discovery when driven by a well defined macromolecular target. Hence, the process is called structure-based or rational drug design (RDD). In the docking step of RDD the macromolecule or receptor is usually considered a rigid body. However, we know from biology that macromolecules such as enzymes and membrane receptors are inherently flexible. Accounting for this flexibility in molecular docking experiments is not trivial. One possibility, which we call a fully-flexible receptor model, is to use a molecular dynamics simulation trajectory of the receptor to simulate its explicit flexibility. To benefit from this concept, which has been known since 2000, it is essential to develop and improve new tools that enable molecular docking simulations of fully-flexible receptor models. We have developed a Flexible-Receptor Docking Workflow System (FReDoWS) to automate molecular docking simulations using a fully-flexible receptor model. In addition, it includes a snapshot selection feature to facilitate acceleration the virtual screening of ligands for well defined disease targets. FReDoWS usefulness is demonstrated by investigating the docking of four different ligands to flexible models of Mycobacterium tuberculosis' wild type InhA enzyme and mutants I21V and I16T. We find that all four ligands bind effectively to this receptor as expected from the literature on similar, but wet experiments. A work that would usually need the manual execution of many computer programs, and the manipulation of thousands of files, was efficiently and automatically performed by FReDoWS. Its friendly interface allows the user to change the docking and execution parameters. Besides, the snapshot selection feature allowed the acceleration of docking simulations. We expect FReDoWS to help us explore more of the role flexibility plays in receptor-ligand interactions. FReDoWS can be made available upon request to the authors.

  19. Modeling oblong proteins and water-mediated interfaces with RosettaDock in CAPRI rounds 28-35.

    Science.gov (United States)

    Marze, Nicholas A; Jeliazkov, Jeliazko R; Roy Burman, Shourya S; Boyken, Scott E; DiMaio, Frank; Gray, Jeffrey J

    2017-03-01

    The 28th-35th rounds of the Critical Assessment of PRotein Interactions (CAPRI) served as a practical benchmark for our RosettaDock protein-protein docking protocols, highlighting strengths and weaknesses of the approach. We achieved acceptable or better quality models in three out of 11 targets. For the two α-repeat protein-green fluorescent protein (αrep-GFP) complexes, we used a novel ellipsoidal partial-global docking method (Ellipsoidal Dock) to generate models with 2.2 Å/1.5 Å interface RMSD, capturing 49%/42% of the native contacts, for the 7-/5-repeat αrep complexes. For the DNase-immunity protein complex, we used a new predictor of hydrogen-bonding networks, HBNet with Bridging Waters, to place individual water models at the complex interface; models were generated with 1.8 Å interface RMSD and 12% native water contacts recovered. The targets for which RosettaDock failed to create an acceptable model were typically difficult in general, as six had no acceptable models submitted by any CAPRI predictor. The UCH-L5-RPN13 and UCH-L5-INO80G de-ubiquitinating enzyme-inhibitor complexes comprised inhibitors undergoing significant structural changes upon binding, with the partners being highly interwoven in the docked complexes. Our failure to predict the nucleosome-enzyme complex in Target 95 was largely due to tight constraints we placed on our model based on sparse biochemical data suggesting two specific cross-interface interactions, preventing the correct structure from being sampled. While RosettaDock's three successes show that it is a state-of-the-art docking method, the difficulties with highly flexible and multi-domain complexes highlight the need for better flexible docking and domain-assembly methods. Proteins 2017; 85:479-486. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Transference, transference interpretations, and transference-focused psychotherapies.

    Science.gov (United States)

    Levy, Kenneth N; Scala, J Wesley

    2012-09-01

    The concept of transference and the use of transference interpretations in psychotherapy have been highly controversial topics garnering frequent attention both within psychoanalysis and across multiple orientations of psychotherapy. In this article, we review the empirical evidence as it bears on this controversy and discuss the implications of the evidence for psychoanalysis, psychodynamic psychotherapy, and therapy in general. We provide a brief historical and contextual overview, followed by a discussion of the development of the concept of transference. We then discuss the evidence for the concept of transference from basic psychological research and contend that these findings are not only consistent with a social-cognitive and information processing model, but that they may also indicate conflict and defensive processes suggestive of a dynamic transference process model. We continue with a discussion of the evidence for the concept of transference from psychotherapy research and examine process findings relating to the use of transference interpretations and transference-focused psychotherapies. Finally, we present the implications of this emerging evidence for clinical practice. PsycINFO Database Record (c) 2012 APA, all rights reserved.

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

    OpenAIRE

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

    2016-01-01

    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. Experi...

  2. Transfer Readiness Pilot Study.

    Science.gov (United States)

    Scott-Skillman, Thelma; And Others

    The California Community Colleges (CCC) has implemented a prototype model for determining student transfer readiness as a primary means of assessing community college transfer effectiveness. This report provides definitions of transfer readiness and guidelines for colleges participating in the CCC transfer readiness study. First, a memorandum from…

  3. Cryogenic heat transfer

    CERN Document Server

    Barron, Randall F

    2016-01-01

    Cryogenic Heat Transfer, Second Edition continues to address specific heat transfer problems that occur in the cryogenic temperature range where there are distinct differences from conventional heat transfer problems. This updated version examines the use of computer-aided design in cryogenic engineering and emphasizes commonly used computer programs to address modern cryogenic heat transfer problems. It introduces additional topics in cryogenic heat transfer that include latent heat expressions; lumped-capacity transient heat transfer; thermal stresses; Laplace transform solutions; oscillating flow heat transfer, and computer-aided heat exchanger design. It also includes new examples and homework problems throughout the book, and provides ample references for further study.

  4. Injurious tail biting in pigs: how can it be controlled in existing systems without tail docking?

    Science.gov (United States)

    D'Eath, R B; Arnott, G; Turner, S P; Jensen, T; Lahrmann, H P; Busch, M E; Niemi, J K; Lawrence, A B; Sandøe, P

    2014-09-01

    Tail biting is a serious animal welfare and economic problem in pig production. Tail docking, which reduces but does not eliminate tail biting, remains widespread. However, in the EU tail docking may not be used routinely, and some 'alternative' forms of pig production and certain countries do not allow tail docking at all. Against this background, using a novel approach focusing on research where tail injuries were quantified, we review the measures that can be used to control tail biting in pigs without tail docking. Using this strict criterion, there was good evidence that manipulable substrates and feeder space affect damaging tail biting. Only epidemiological evidence was available for effects of temperature and season, and the effect of stocking density was unclear. Studies suggest that group size has little effect, and the effects of nutrition, disease and breed require further investigation. The review identifies a number of knowledge gaps and promising avenues for future research into prevention and mitigation. We illustrate the diversity of hypotheses concerning how different proposed risk factors might increase tail biting through their effect on each other or on the proposed underlying processes of tail biting. A quantitative comparison of the efficacy of different methods of provision of manipulable materials, and a review of current practices in countries and assurance schemes where tail docking is banned, both suggest that daily provision of small quantities of destructible, manipulable natural materials can be of considerable benefit. Further comparative research is needed into materials, such as ropes, which are compatible with slatted floors. Also, materials which double as fuel for anaerobic digesters could be utilised. As well as optimising housing and management to reduce risk, it is important to detect and treat tail biting as soon as it occurs. Early warning signs before the first bloody tails appear, such as pigs holding their tails tucked

  5. Thermal radiation heat transfer

    CERN Document Server

    Howell, John R; Siegel, Robert

    2016-01-01

    Further expanding on the changes made to the fifth edition, Thermal Radiation Heat Transfer, 6th Edition continues to highlight the relevance of thermal radiative transfer and focus on concepts that develop the radiative transfer equation (RTE). The book explains the fundamentals of radiative transfer, introduces the energy and radiative transfer equations, covers a variety of approaches used to gauge radiative heat exchange between different surfaces and structures, and provides solution techniques for solving the RTE.

  6. Effect in dedicator of cytokinesis 6 (DOCK6) on steroid production in theca cells of follicular cysts.

    Science.gov (United States)

    Murayama, Chiaki; Yamasaki, Eiki; Miyamoto, Akio; Shimizu, Takashi

    2015-07-10

    Ovarian follicular cysts are one of the most common causes of reproductive failure in mammals. A comparative gene expression approach may aid in elucidating the causes of ovarian cyst disease. In the present study, the differential display technique was used to identify mRNA sequences that accumulate preferentially in theca cells of bovine cystic follicles. Dedicator of cytokinesis 6 (Dock6) expression was observed in the theca cells of cystic follicles. Small interfering RNA (siRNA) knockdown of Dock6 increased progesterone (P4) production and StAR expression in theca cells of high-estrogen follicular cysts, but did not affect androstenedione (A4) production. We propose that Dock6 may be a marker associated with the development of follicular cysts. Additionally, Dock6 may be involved in the development of cystic follicles by suppressing P4 production rather than increasing A4 production in theca cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Prediction of binding poses to FXR using multi-targeted docking combined with molecular dynamics and enhanced sampling

    Science.gov (United States)

    Bhakat, Soumendranath; Åberg, Emil; Söderhjelm, Pär

    2017-10-01

    Advanced molecular docking methods often aim at capturing the flexibility of the protein upon binding to the ligand. In this study, we investigate whether instead a simple rigid docking method can be applied, if combined with multiple target structures to model the backbone flexibility and molecular dynamics simulations to model the sidechain and ligand flexibility. The methods are tested for the binding of 35 ligands to FXR as part of the first stage of the Drug Design Data Resource (D3R) Grand Challenge 2 blind challenge. The results show that the multiple-target docking protocol performs surprisingly well, with correct poses found for 21 of the ligands. MD simulations started on the docked structures are remarkably stable, but show almost no tendency of refining the structure closer to the experimentally found binding pose. Reconnaissance metadynamics enhances the exploration of new binding poses, but additional collective variables involving the protein are needed to exploit the full potential of the method.

  8. Estimation of Inhibitory Effect against Tyrosinase Activity through Homology Modeling and Molecular Docking

    Directory of Open Access Journals (Sweden)

    Daungkamon Nokinsee

    2015-01-01

    Full Text Available Tyrosinase is a key enzyme in melanogenesis. Generally, mushroom tyrosinase from A. bisporus had been used as a model in skin-whitening agent tests employed in the cosmetic industry. The recently obtained crystal structure of bacterial tyrosinase from B. megaterium has high similarity (33.5% to the human enzyme and thus it was used as a template for constructing of the human model. Binding of tyrosinase to a series of its inhibitors was simulated by automated docking calculations. Docking and MD simulation results suggested that N81, N260, H263, and M280 are involved in the binding of inhibitors to mushroom tyrosinase. E195 and H208 are important residues in bacterial tyrosinase, while E230, S245, N249, H252, V262, and S265 bind to inhibitors and are important in forming pi interaction in human tyrosinase.

  9. Autonomous Docking Based on Infrared System for Electric Vehicle Charging in Urban Areas

    Directory of Open Access Journals (Sweden)

    Joshué Pérez

    2013-02-01

    Full Text Available Electric vehicles are progressively introduced in urban areas, because of their ability to reduce air pollution, fuel consumption and noise nuisance. Nowadays, some big cities are launching the first electric car-sharing projects to clear traffic jams and enhance urban mobility, as an alternative to the classic public transportation systems. However, there are still some problems to be solved related to energy storage, electric charging and autonomy. In this paper, we present an autonomous docking system for electric vehicles recharging based on an embarked infrared camera performing infrared beacons detection installed in the infrastructure. A visual servoing system coupled with an automatic controller allows the vehicle to dock accurately to the recharging booth in a street parking area. The results show good behavior of the implemented system, which is currently deployed as a real prototype system in the city of Paris.

  10. Autonomous docking based on infrared system for electric vehicle charging in urban areas.

    Science.gov (United States)

    Pérez, Joshué; Nashashibi, Fawzi; Lefaudeux, Benjamin; Resende, Paulo; Pollard, Evangeline

    2013-02-21

    Electric vehicles are progressively introduced in urban areas, because of their ability to reduce air pollution, fuel consumption and noise nuisance. Nowadays, some big cities are launching the first electric car-sharing projects to clear traffic jams and enhance urban mobility, as an alternative to the classic public transportation systems. However, there are still some problems to be solved related to energy storage, electric charging and autonomy. In this paper, we present an autonomous docking system for electric vehicles recharging based on an embarked infrared camera performing infrared beacons detection installed in the infrastructure. A visual servoing system coupled with an automatic controller allows the vehicle to dock accurately to the recharging booth in a street parking area. The results show good behavior of the implemented system, which is currently deployed as a real prototype system in the city of Paris.

  11. Novel α, β-Unsaturated Sophoridinic Derivatives: Design, Synthesis, Molecular Docking and Anti-Cancer Activities

    Directory of Open Access Journals (Sweden)

    Yiming Xu

    2017-11-01

    Full Text Available Using sophoridine 1 and chalcone 3 as the lead compounds, a series of novel α, β-unsaturated sophoridinic derivatives were designed, synthesized, and evaluated for their in vitro cytotoxicity. Structure-activity relationship (SAR analysis indicated that introduction of α, β-unsaturated ketone moiety and heterocyclic group might significantly enhance anticancer activity. Among the compounds, 2f and 2m exhibited potential effects against HepG-2 and CNE-2 human cancer cell lines. Furthermore, molecular docking studies were performed to understand possible docking sites of the molecules on the target proteins and the mode of binding. This work provides a theoretical basis for structural optimizations and exploring anticancer pathways of this kind of compound.

  12. Assessment and Challenges of Ligand Docking into Comparative Models of G-Protein Coupled Receptors

    DEFF Research Database (Denmark)

    Nguyen, E.D.; Meiler, J.; Norn, C.

    2013-01-01

    The rapidly increasing number of high-resolution X-ray structures of G-protein coupled receptors (GPCRs) creates a unique opportunity to employ comparative modeling and docking to provide valuable insight into the function and ligand binding determinants of novel receptors, to assist in virtual...... and side-chain conformational space with Rosetta can be leveraged to meet this challenge. This study performs unbiased comparative modeling and docking methodologies using 14 distinct high-resolution GPCRs and proposes knowledge-based filtering methods for improvement of sampling performance...... and identification of correct ligand-receptor interactions. On average, top ranked receptor models built on template structures over 50% sequence identity are within 2.9 Å of the experimental structure, with an average root mean square deviation (RMSD) of 2.2 Å for the transmembrane region and 5 Å for the second...

  13. A Velocity-Based Impedance Control System for a Low Impact Docking Mechanism (LIDM

    Directory of Open Access Journals (Sweden)

    Chuanzhi Chen

    2014-12-01

    Full Text Available In this paper, an impedance control algorithm based on velocity for capturing two low impact docking mechanisms (LIDMs is presented. The main idea of this algorithm is to track desired forces when the position errors of two LIDMs are random by designing the relationship between the velocity and contact forces measured by a load sensing ring to achieve low impact docking. In this paper, the governing equation of an impedance controller between the deviation of forces and velocity is derived, and simulations are designed to verify how impedance parameters affect the control characteristics. The performance of the presented control algorithm is validated by using the MATLAB and ADAMS software for capturing simulations. The results of capturing simulations demonstrate that the impedance control algorithm can respond fast and has excellent robustness when the environmental errors are random, and the contact forces and torques satisfy the low impact requirements.

  14. Computational evaluation of some indenopyrazole derivatives as anticancer compounds; application of QSAR and docking methodologies.

    Science.gov (United States)

    Shahlaei, Mohsen; Fassihi, Afshin; Saghaie, Lotfollah; Arkan, Elham; Madadkar-Sobhani, Armin; Pourhossein, Alireza

    2013-02-01

    A computational procedure was performed on some indenopyrazole derivatives. Two important procedures in computational drug discovery, namely docking for modeling ligand-receptor interactions and quantitative structure activity relationships were employed. MIA-QSAR analysis of the studied derivatives produced a model with high predictability. The developed model was then used to evaluate the bioactivity of 54 proposed indenopyrazole derivatives. In order to confirm the obtained results through this ligand-based method, docking was performed on the selected compounds. An ADME-Tox evaluation was also carried out to search for more suitable compounds. Satisfactory bioactivities and ADME-Tox profiles for two of the compounds, namely 62 and S13, propose that further studies should be performed on such devoted chemical structures.

  15. 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.

  16. Inhibitors of Human Dihydrofolate Reductase: A Computational Design and Docking Studies Using Glide

    Directory of Open Access Journals (Sweden)

    Lingala Yamini

    2008-01-01

    Full Text Available Dihydrofolate reductase (DHFR plays a vital role in the DNA synthesis by reducing dihydrofolic acid to tetrahydrofolic acid which is an essential component. Synthetic ligands like methotrexate (MTX, aminopterin (AMP and their analogues act as potential anti metabolites by mimicking the coenzyme dihydrofolic acid (DHFA they inhibit the activity of DHFR antagonistically. Several ligands which are similar to MTX analogues and 6, 8 substituted 2 – naphthyls (NAP which can mimic the pteridyl group of DHFA have been computationally designed. These ligands were proposed to hinder the formation N5, N10 methylene tetrahydrofolic acid (THFA coenzyme, which is essential for the DNA synthesis. The docking studies were done using grid, generated with the 0.9 Vander Waals scaling for non polar bonds in the active site of the receptor. These newly designed ligands such as 14 -21 ,23 and 28 have shown good docking scores and predicted activities when compared to already existing ligands MTX and its analogues.

  17. Docking studies: In silico lipoxygenase inhibitory activity of some commercially available flavonoids

    Directory of Open Access Journals (Sweden)

    Arumugam Madeswaran

    2011-06-01

    Full Text Available This study deals with the evaluation of the cyclooxygenase inhibitory activity of flavonoids using in silico docking studies. In this perspective, flavonoids like morin, naringenin, taxifolin, esculatin, daidzein, genistein, scopoletin, galangin and silbinin were selected. Azelastine, a known lipoxygenase inhibitor was used as the standard. Docking results showed that all the selected flavonoids showed binding energy ranging between -3.93 kcal/mol to -3.36 kcal/mol when compared with that of the standard (-3.70 kcal/mol. Intermolecular energy (-5.72 kcal/mol to -4.56 kcal/mol and inhibition constant (1.31 mM to 3.43 mM of the ligands also coincide with the binding energy. Morin contributed better lipoxygenase inhibitory activity because of its structural parameters.

  18. Natural Products as New Treatment Options for Trichomoniasis: A Molecular Docking Investigation

    Science.gov (United States)

    Snow Setzer, Mary; Byler, Kendall G.; Ogungbe, Ifedayo Victor; Setzer, William N.

    2017-01-01

    Trichomoniasis, caused by the parasitic protozoan Trichomonas vaginalis, is the most common non-viral sexually-transmitted disease, and there can be severe complications from trichomoniasis. Antibiotic resistance in T. vaginalis is increasing, but there are currently no alternatives treatment options. There is a need to discover and develop new chemotherapeutic alternatives. Plant-derived natural products have long served as sources for new medicinal agents, as well as new leads for drug discovery and development. In this work, we have carried out an in silico screening of 952 antiprotozoal phytochemicals with specific protein drug targets of T. vaginalis. A total of 42 compounds showed remarkable docking properties to T. vaginalis methionine gamma-lyase (TvMGL) and to T. vaginalis purine nucleoside phosphorylase (TvPNP). The most promising ligands were polyphenolic compounds, and several of these showed docking properties superior to either co-crystallized ligands or synthetic enzyme inhibitors. PMID:28134827

  19. Four-arm single docking full robotic surgery for low rectal cancer: technique standardization

    Directory of Open Access Journals (Sweden)

    José Reinan Ramos

    Full Text Available The authors present the four-arm single docking full robotic surgery to treat low rectal cancer. The eight main operative steps are: 1- patient positioning; 2- trocars set-up and robot docking; 3- sigmoid colon, left colon and splenic flexure mobilization (lateral-to-medial approach; 4-Inferior mesenteric artery and vein ligation (medial-to-lateral approach; 5- total mesorectum excision and preservation of hypogastric and pelvic autonomic nerves (sacral dissection, lateral dissection, pelvic dissection; 6- division of the rectum using an endo roticulator stapler for the laparoscopic performance of a double-stapled coloanal anastomosis (type I tumor; 7- intersphincteric resection, extraction of the specimen through the anus and lateral-to-end hand sewn coloanal anastomosis (type II tumor; 8- cylindric abdominoperineal resection, with transabdominal section of the levator muscles (type IV tumor. The techniques employed were safe and have presented low rates of complication and no mortality.

  20. Flattop regulates basal body docking and positioning in mono- and multiciliated cells.

    Science.gov (United States)

    Gegg, Moritz; Böttcher, Anika; Burtscher, Ingo; Hasenoeder, Stefan; Van Campenhout, Claude; Aichler, Michaela; Walch, Axel; Grant, Seth G N; Lickert, Heiko

    2014-10-08

    Planar cell polarity (PCP) regulates basal body (BB) docking and positioning during cilia formation, but the underlying mechanisms remain elusive. In this study, we investigate the uncharacterized gene Flattop (Fltp) that is transcriptionally activated during PCP acquisition in ciliated tissues. Fltp knock-out mice show BB docking and ciliogenesis defects in multiciliated lung cells. Furthermore, Fltp is necessary for kinocilium positioning in monociliated inner ear hair cells. In these cells, the core PCP molecule Dishevelled 2, the BB/spindle positioning protein Dlg3, and Fltp localize directly adjacent to the apical plasma membrane, physically interact and surround the BB at the interface of the microtubule and actin cytoskeleton. Dlg3 and Fltp knock-outs suggest that both cooperatively translate PCP cues for BB positioning in the inner ear. Taken together, the identification of novel BB/spindle positioning components as potential mediators of PCP signaling might have broader implications for other cell types, ciliary disease, and asymmetric cell division.

  1. Understanding of empty container movement: A study on a bottleneck at an off-dock depot

    Science.gov (United States)

    Zain, Rosmaizura Mohd; Rahman, Mohd Nizam Ab; Nopiah, Zulkifli Mohd; Saibani, Nizaroyani

    2014-09-01

    Port not only function as connections between marine and land transportation but also as core business areas. In a port terminal, available space is limited, but the influx of container is growing. The off-dock depot is one of the key supply chain players that hold empty containers in the inventory. Therefore, this paper aims to identify the main factors of bottlenecks or congestion that hinder the rapid movement of empty containers from the off-dock depot to the customers. Thirty interviews were conducted with individuals who are key players in the container supply chain. The data were analyzed using Atlas.ti software and the analytic hierarchy process to rank the priority factors of bottlenecks. Findings show that several pertinent factors act as barriers to the key players in the container movement in the day-to-day operations. In future studies, strategies to overcome fragmentation in the container supply chain and logistics must be determined.

  2. Design of a positioning system for soft-docking of an intraoperative electron accelerator

    Science.gov (United States)

    Soboń, Rafał; Wysocka-Rabin, Anna; Golnik, Natalia

    2013-10-01

    A soft-docking system is one of the features of modern intraoperative radiotherapy (IORT) technology. It permits delivery of a single fraction of radiation to the surgically exposed tissue, whilst the treatment head is not in direct contact with the applicator. The aim of this study is to present the design of the positioning system for soft-docking of mobile linear accelerator that is being developed at the National Centre of Nuclear Research in Otwock-Świerk, Poland (NCBJ). Our proposed design includes four red laser beams installed along with the treatment head, and a specially prepared applicator with a pre-drawn reference circle. When the treatment head is correctly positioned, all four laser dots intersect with the circle. Numerical simulation showed that it is possible to minimize misalignment to around 0.5° angular and 1 mm linear with this model.

  3. 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

    2016-08-31

    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.

  4. Dock Sud's environmental pollution: Spatial representations, space representation and spatial practices in peripheral neighborhoods

    Directory of Open Access Journals (Sweden)

    Sandra Valeria Ursino

    2012-01-01

    Full Text Available In this article, we present some of the results and argumentative lines used in the analysis of the field work carried out in the neighborhoods of Porst, Danubio and Villa Inflamable, in the Dock Sud area, located in the district of Avellaneda, province de Buenos Aires, during 2010 and 2011. Within this framework, we observed and recorded the inhabitants' usual routes around the neighborhood, which is environmentally polluted but which has also been symbolically appropriated. Along these lines then, our general aim was to learn about social representations, representation spaces and the spatial practices of the inhabitants of the most affected neighborhoods of Dock Sud due to the area's environmental issues. To this end, there was a reconstruction of the subjects' practices in the neighborhood, of the hegemonic discourse about the pollution in this place and, finally, the population's conflict and struggle practices

  5. Natural Products as New Treatment Options for Trichomoniasis: A Molecular Docking Investigation

    Directory of Open Access Journals (Sweden)

    Mary Snow Setzer

    2017-01-01

    Full Text Available Trichomoniasis, caused by the parasitic protozoan Trichomonas vaginalis, is the most common non-viral sexually-transmitted disease, and there can be severe complications from trichomoniasis. Antibiotic resistance in T. vaginalis is increasing, but there are currently no alternatives treatment options. There is a need to discover and develop new chemotherapeutic alternatives. Plant-derived natural products have long served as sources for new medicinal agents, as well as new leads for drug discovery and development. In this work, we have carried out an in silico screening of 952 antiprotozoal phytochemicals with specific protein drug targets of T. vaginalis. A total of 42 compounds showed remarkable docking properties to T. vaginalis methionine gamma-lyase (TvMGL and to T. vaginalis purine nucleoside phosphorylase (TvPNP. The most promising ligands were polyphenolic compounds, and several of these showed docking properties superior to either co-crystallized ligands or synthetic enzyme inhibitors.

  6. Hydrogen bond docking preference in furans: OH⋯π vs. OH⋯O.

    Science.gov (United States)

    Jiang, Xiaotong; Tsona, Narcisse T; Tang, Shanshan; Du, Lin

    2018-02-15

    The docking sites of hydrogen bonds in complexes formed between 2,2,2-trifluoroethanol (TFE), furan (Fu), and 2-methyl furan (MF) have been investigated. Using density functional theory (DFT) calculations, gas phase and matrix isolation FTIR spectroscopies, the strengths of OH⋯O and OH⋯π hydrogen bonds in the complexes were compared to find the docking preference. Calculations suggest that the hydrogen bond donor, TFE, is more likely to dock onto the oxygen atom of the aromatic furans ring, and consequently, the OH⋯O type hydrogen bond is relatively stronger than the OH⋯π type. The FTIR spectrum in the OH-stretching fundamental range obtained at room temperatures has been compared with that obtained at extremely low temperatures in the matrix. The fundamental and the red shifts of OH-stretching vibrations were observed in both FTIR spectra, confirming the formation of hydrogen bonded complexes. By assessing the ability of furan and MF to participate in the formation of OH⋯O hydrogen bond, the effect of ring methylation has been highlighted. From the calculated geometric and thermodynamic parameters as well as the frequency shift of the OH-stretching vibrations in complexes, TFE-MF is found to be more stable than TFE-Fu, which suggests that the strength of the OH⋯O hydrogen bond in TFE-MF originates from the high activity of the furan molecule caused by the methylation of the aromatic ring. The present study furthers the knowledge of docking preference in heteroaromatic molecules and is helpful to understand the nature of intermolecular interactions between hydrogen bond donors and acceptors, including both electron-deficient atoms and π cloud. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Logistics and operations implications of manual control of spacecraft docking maneuvers

    Science.gov (United States)

    Brody, Adam R.; Ellis, Stephen R.

    The implications of logistics and operations on the manual control of spacecraft docking are discussed. The results of simulation studies to investigate fuel and time cost tradeoffs are reviewed and discussed. Comparisons of acceleration control and pulse control are presented to evaluate the effects of astronauts being instructed to use pulse mode for fuel conservation. The applications of the findings to moon and Mars missions are addressed.

  8. Hydrogen bond docking preference in furans: Osbnd H ⋯ π vs. Osbnd H ⋯ O

    Science.gov (United States)

    Jiang, Xiaotong; Tsona, Narcisse T.; Tang, Shanshan; Du, Lin

    2018-02-01

    The docking sites of hydrogen bonds in complexes formed between 2,2,2-trifluoroethanol (TFE), furan (Fu), and 2-methyl furan (MF) have been investigated. Using density functional theory (DFT) calculations, gas phase and matrix isolation FTIR spectroscopies, the strengths of Osbnd H ⋯ O and Osbnd H ⋯ π hydrogen bonds in the complexes were compared to find the docking preference. Calculations suggest that the hydrogen bond donor, TFE, is more likely to dock onto the oxygen atom of the aromatic furans ring, and consequently, the Osbnd H ⋯ O type hydrogen bond is relatively stronger than the Osbnd H ⋯ π type. The FTIR spectrum in the OH-stretching fundamental range obtained at room temperatures has been compared with that obtained at extremely low temperatures in the matrix. The fundamental and the red shifts of OH-stretching vibrations were observed in both FTIR spectra, confirming the formation of hydrogen bonded complexes. By assessing the ability of furan and MF to participate in the formation of Osbnd H ⋯ O hydrogen bond, the effect of ring methylation has been highlighted. From the calculated geometric and thermodynamic parameters as well as the frequency shift of the OH-stretching vibrations in complexes, TFE-MF is found to be more stable than TFE-Fu, which suggests that the strength of the Osbnd H ⋯ O hydrogen bond in TFE-MF originates from the high activity of the furan molecule caused by the methylation of the aromatic ring. The present study furthers the knowledge of docking preference in heteroaromatic molecules and is helpful to understand the nature of intermolecular interactions between hydrogen bond donors and acceptors, including both electron-deficient atoms and π cloud.

  9. Novel Penicillin Analogues as Potential Antimicrobial Agents; Design, Synthesis and Docking Studies.

    Science.gov (United States)

    Ashraf, Zaman; Bais, Abdul; Manir, Md Maniruzzaman; Niazi, Umar

    2015-01-01

    A number of penicillin derivatives (4a-h) were synthesized by the condensation of 6-amino penicillinic acid (6-APA) with non-steroidal anti-inflammatory drugs as antimicrobial agents. In silico docking study of these analogues was performed against Penicillin Binding Protein (PDBID 1CEF) using AutoDock Tools 1.5.6 in order to investigate the antimicrobial data on structural basis. Penicillin binding proteins function as either transpeptidases or carboxypeptidases and in few cases demonstrate transglycosylase activity in bacteria. The excellent antibacterial potential was depicted by compounds 4c and 4e against Escherichia coli, Staphylococcus epidermidus and Staphylococcus aureus compared to the standard amoxicillin. The most potent penicillin derivative 4e exhibited same activity as standard amoxicillin against S. aureus. In the enzyme inhibitory assay the compound 4e inhibited E. coli MurC with an IC50 value of 12.5 μM. The docking scores of these compounds 4c and 4e also verified their greater antibacterial potential. The results verified the importance of side chain functionalities along with the presence of central penam nucleus. The binding affinities calculated from docking results expressed in the form of binding energies ranges from -7.8 to -9.2kcal/mol. The carboxylic group of penam nucleus in all these compounds is responsible for strong binding with receptor protein with the bond length ranges from 3.4 to 4.4 Ǻ. The results of present work ratify that derivatives 4c and 4e may serve as a structural template for the design and development of potent antimicrobial agents.

  10. Sedimentation problems in a lateral dock on the Paraná River

    Science.gov (United States)

    Latessa, Gaston; Sabarots Gerbec, Martin; Arecco, Pablo

    2017-04-01

    The Paraná River is one of the largest water courses in the world and along its reach in the Argentine territory, it receives a large load of sediments from the Pilcomayo and Bermejo Rivers, through the Paraguay River, in the upper basin at the North of Argentina and South of Bolivia. The suspended sediment load is estimated in 100 Million ton/year. This unique characteristic drives the Paraná River morphology downstream, as well as the Paraná delta morphodynamics. On top of its natural behaviour, the Paraná-Paraguay river system is an important inland waterway transport corridor, with a significant amount of sea going vessels and inland barges navigating throughout stretches of more than 3000 Km. Consequently, there are numerous port complexes and terminals along the river banks. The typical wet infrastructure of these terminals is usually composed by jetties and quay walls, and occasionally with side or lateral docks. Whereas, the case included within this study presents all these components. This study presents a hydrodynamic and sedimentology 3D model to predict the velocity fields and the associated shear stresses that will drive morphological processes in the lateral dock. The terminal layout, side dock configuration, and sedimentation issues will be analyzed from multidisciplinary point of view, under different hydrological events and considering the correlated sediment loads. Recent bathymetry studies had been carried out and this set of data will be implemented to build the domain geometry. The flow series is as well extended with the up to date gauged flows and levels, to carry out statistical analysis and identify the design flows for different probabilities. The main objective of this analysis will be to understand and identify the scour and deposition processes and the possible problems to the structures safety and the operation of the docks, and introduce variations to the baseline design, if necessary. Results will be contrasted and validated

  11. Interactions of cephalexin with bovine serum albumin: displacement reaction and molecular docking

    Directory of Open Access Journals (Sweden)

    Hamed Hamishehkar

    2016-09-01

    Conclusion: The outcomes of spectroscopic methods revealed that the conformation of BSA changed during drug-BSA interaction. The results of FRET propose that CPL quenches the fluorescence of BSA by static quenching and FRET. The displacement study showed that phenylbutazon and ketoprofen displaced CPL, indicating that its binding site on albumin is site I and Gentamicin cannot be displaced from the binding site of CPL. All results of molecular docking method agreed with the results of experimental data.

  12. Discovery of an Interleukin 33 Inhibitor by Molecular Docking Simulation and NMR Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Kwan; Cho, Sang Hyun; Mushtaq, Ameeq UI; Jung, Yong Woo; Byun, Youngjoo; Jeon, Young Ho [Korea University, Sejong (Korea, Republic of); Cho, Haelim [T and J Tech Inc., Seoul (Korea, Republic of)

    2016-02-15

    We identified an inhibitor, which is able to bind to the IL-33 and potentially interfere with ST2 binding by means of docking-based virtual screening and 2D NMR binding analyses. Using this compound, the NMR Chemical shift perturbation (CSP) of IL-33 signals were analyzed and mapped on the structure of IL-33, showing that the identified compound binds at the interface of IL-33 and ST2 binding.

  13. Off the Waterfront: The long-run impact of technological change on dock workers

    OpenAIRE

    El-Sahli, Zouheir; Upward, Richard

    2015-01-01

    We investigate how individual workers and local labour markets adjust over a long time period to a discrete and plausibly exogenous technological shock, namely the introduction of containerisation in the UK port industry. This technology, which was introduced rapidly between the mid-1960s and the late-1970s, had dramatic consequences for specific occupations within the port industry. Using longitudinal micro-census data we follow dock-workers over a 40 year period and examine the long-run c...

  14. Synthesis, Antibacterial Activity, Interaction with Nucleobase and Molecular Docking Studies of 4-Formylbenzoic Acid Based Thiazoles.

    Science.gov (United States)

    Laczkowski, Krzysztof Z; Biernasiuk, Anna; Baranowska-Laczkowska, Angelika; Misiura, Konrad; Malm, Anna; Plech, Tomasz; Paneth, Agata

    2016-01-01

    Synthesis, characterization and investigation of antibacterial activity of ten novel Schiff base derivatives of 4-formylbenzoic acid is presented. Their structures were determined using 1H and 13CNMR, EI(+)-MS and elemental analyses. Additionally, DFT calculations of interaction energies in complexes of the novel drugs and DNA bases are carried out. Design and synthesis of thiazole derivatives with benzoic acid scaffold to obtain compounds with an improved antibacterial activity. The examined compounds were screened in vitro for antibacterial activity using the broth microdilution method. Geometrical parameters of the investigated complexes were optimized within the Density Functional Theory (DFT) approximation using the B3LYP functional and the 6-311G** basis set. The docking simulations were performed using the FlexX docking module. Among the derivatives, compound 4b showed very strong bacterial activity against staphylococci, MIC 1.95-3.91 µg/ml, micrococci, MIC 0.98 µg/ml, and Bacillus spp., MIC 7.81-15.62 µg/ml. The compounds 4c, 4d, 4e and 4j also showed high bioactivity against staphylococci, MIC 3.91-31.25 µg/ml, and micrococci, MIC 0.98-15.62 µg/ml. Interaction energy values for investigated guanine complexes are about 2 kcal/mol lower than for the corresponding cytosine complexes. Molecular docking studies of all compounds on the active sites of bacterial enzymes indicated gyrase B as possible target. To conclude, an efficient and economic method for the synthesis of thiazoles containing benzoic acid moiety has been developed. The results of antibacterial screenings reveal that some obtained compounds show high to very strong antibacterial activity. The DFT calculations showed that interaction of the obtained drugs with guanine is stronger than with cytosine. Molecular docking studies of all compounds on the active sites of bacterial enzymes indicated gyrase B as possible target.

  15. Protein–protein docking by fast generalized Fourier transforms on 5D rotational manifolds

    Science.gov (United States)

    Padhorny, Dzmitry; Kazennov, Andrey; Zerbe, Brandon S.; Porter, Kathryn A.; Xia, Bing; Mottarella, Scott E.; Kholodov, Yaroslav; Ritchie, David W.; Vajda, Sandor; Kozakov, Dima

    2016-01-01

    Energy evaluation using fast Fourier transforms (FFTs) enables sampling billions of putative complex structures and hence revolutionized rigid protein–protein docking. However, in current methods, efficient acceleration is achieved only in either the translational or the rotational subspace. Developing an efficient and accurate docking method that expands FFT-based sampling to five rotational coordinates is an extensively studied but still unsolved problem. The algorithm presented here retains the accuracy of earlier methods but yields at least 10-fold speedup. The improvement is due to two innovations. First, the search space is treated as the product manifold SO(3)×(SO(3)∖S1), where SO(3) is the rotation group representing the space of the rotating ligand, and (SO(3)∖S1) is the space spanned by the two Euler angles that define the orientation of the vector from the center of the fixed receptor toward the center of the ligand. This representation enables the use of efficient FFT methods developed for SO(3). Second, we select the centers of highly populated clusters of docked structures, rather than the lowest energy conformations, as predictions of the complex, and hence there is no need for very high accuracy in energy evaluation. Therefore, it is sufficient to use a limited number of spherical basis functions in the Fourier space, which increases the efficiency of sampling while retaining the accuracy of docking results. A major advantage of the method is that, in contrast to classical approaches, increasing the number of correlation function terms is computationally inexpensive, which enables using complex energy functions for scoring. PMID:27412858

  16. Total robotic radical rectal resection with da Vinci Xi system: single docking, single phase technique.

    Science.gov (United States)

    Tamhankar, Anup Sunil; Jatal, Sudhir; Saklani, Avanish

    2016-12-01

    This study aims to assess the advantages of Da Vinci Xi system in rectal cancer surgery. It also assesses the initial oncological outcomes after rectal resection with this system from a tertiary cancer center in India. Robotic rectal surgery has distinct advantages over laparoscopy. Total robotic resection is increasing following the evolution of hybrid technology. The latest Da Vinci Xi system (Intuitive Surgical, Sunnyvale, USA) is enabled with newer features to make total robotic resection possible with single docking and single phase. Thirty-six patients underwent total robotic resection in a single phase and single docking. We used newer port positions in a straight line. Median distance from the anal verge was 4.5 cm. Median robotic docking time and robotic procedure time were 9 and 280 min, respectively. Median blood loss was 100 mL. One patient needed conversion to an open approach due to advanced disease. Circumferential resection margin and longitudinal resection margins were uninvolved in all other patients. Median lymph node yield was 10. Median post-operative stay was 7 days. There were no intra-operative adverse events. The latest Da Vinci Xi system has made total robotic rectal surgery feasible in single docking and single phase. With the new system, four arm total robotic rectal surgery may replace the hybrid technique of laparoscopic and robotic surgery for rectal malignancies. The learning curve for the new system appears to be shorter than anticipated. Early perioperative and oncological outcomes of total robotic rectal surgery with the new system are promising. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  17. Molecular Docking Studies and Anti-Tyrosinase Activity of Thai Mango Seed Kernel Extract

    OpenAIRE

    Patchreenart Saparpakorn; Rapepol Bavovada; Pimolpan Pithayanukul; Saruth Nithitanakool

    2009-01-01

    The alcoholic extract from seed kernels of Thai mango (Mangifera indica L. cv. ‘Fahlun’) (Anacardiaceae) and its major phenolic principle (pentagalloylglucopyranose) exhibited potent, dose-dependent inhibitory effects on tyrosinase with respect to L-DOPA. Molecular docking studies revealed that the binding orientations of the phenolic principles were in the tyrosinase binding pocket and their orientations were located in the hydrophobic binding pocket surrounding the binuclear coppe...

  18. Novel Penicillin Analogues as Potential Antimicrobial Agents; Design, Synthesis and Docking Studies.

    Directory of Open Access Journals (Sweden)

    Zaman Ashraf

    Full Text Available A number of penicillin derivatives (4a-h were synthesized by the condensation of 6-amino penicillinic acid (6-APA with non-steroidal anti-inflammatory drugs as antimicrobial agents. In silico docking study of these analogues was performed against Penicillin Binding Protein (PDBID 1CEF using AutoDock Tools 1.5.6 in order to investigate the antimicrobial data on structural basis. Penicillin binding proteins function as either transpeptidases or carboxypeptidases and in few cases demonstrate transglycosylase activity in bacteria. The excellent antibacterial potential was depicted by compounds 4c and 4e against Escherichia coli, Staphylococcus epidermidus and Staphylococcus aureus compared to the standard amoxicillin. The most potent penicillin derivative 4e exhibited same activity as standard amoxicillin against S. aureus. In the enzyme inhibitory assay the compound 4e inhibited E. coli MurC with an IC50 value of 12.5 μM. The docking scores of these compounds 4c and 4e also verified their greater antibacterial potential. The results verified the importance of side chain functionalities along with the presence of central penam nucleus. The binding affinities calculated from docking results expressed in the form of binding energies ranges from -7.8 to -9.2kcal/mol. The carboxylic group of penam nucleus in all these compounds is responsible for strong binding with receptor protein with the bond length ranges from 3.4 to 4.4 Ǻ. The results of present work ratify that derivatives 4c and 4e may serve as a structural template for the design and development of potent antimicrobial agents.

  19. Molecular docking as a popular tool in drug design, an in silico travel

    OpenAIRE

    de Ruyck, Jerome; Brysbaert, Guillaume; Blossey, Ralf; Lensink, Marc F

    2016-01-01

    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 mecha...

  20. Docking and QSAR Studies of Camptothecin Derivatives as Inhibitor of DNA Topoisomerase-I

    OpenAIRE

    Dharmendra K. Yadav; Feroz Khan; Srivastava, Santosh K.

    2011-01-01

    Camptothecin (CPT) is a cytotoxic quinoline alkaloid which inhibits the DNA enzyme Topoisomerase-I (Topo-I) and has shown remarkable anticancer activity in preliminary clinical trials. The major limitation is its low solubility and high adverse reaction. In the studied work, we performed molecular docking of CPT derivatives against Topo-I and developed the quantitative structure activity relationship (QSAR) model for anticancer activity screening. For QSAR, we used CPT and other anticancer dr...

  1. Differential regulation of protein tyrosine kinase signalling by Dock and the PTP61F variants.

    Science.gov (United States)

    Willoughby, Lee F; Manent, Jan; Allan, Kirsten; Lee, Han; Portela, Marta; Wiede, Florian; Warr, Coral; Meng, Tzu-Ching; Tiganis, Tony; Richardson, Helena E

    2017-07-01

    Tyrosine phosphorylation-dependent signalling is coordinated by the opposing actions of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). There is a growing list of adaptor proteins that interact with PTPs and facilitate the dephosphorylation of substrates. The extent to which any given adaptor confers selectivity for any given substrate in vivo remains unclear. Here we have taken advantage of Drosophila melanogaster as a model organism to explore the influence of the SH3/SH2 adaptor protein Dock on the abilities of the membrane (PTP61Fm)- and nuclear (PTP61Fn)-targeted variants of PTP61F (the Drosophila othologue of the mammalian enzymes PTP1B and TCPTP respectively) to repress PTK signalling pathways in vivo. PTP61Fn effectively repressed the eye overgrowth associated with activation of the epidermal growth factor receptor (EGFR), PTK, or the expression of the platelet-derived growth factor/vascular endothelial growth factor receptor (PVR) or insulin receptor (InR) PTKs. PTP61Fn repressed EGFR and PVR-induced mitogen-activated protein kinase signalling and attenuated PVR-induced STAT92E signalling. By contrast, PTP61Fm effectively repressed EGFR- and PVR-, but not InR-induced tissue overgrowth. Importantly, coexpression of Dock with PTP61F allowed for the efficient repression of the InR-induced eye overgrowth, but did not enhance the PTP61Fm-mediated inhibition of EGFR and PVR-induced signalling. Instead, Dock expression increased, and PTP61Fm coexpression further exacerbated the PVR-induced eye overgrowth. These results demonstrate that Dock selectively enhances the PTP61Fm-mediated attenuation of InR signalling and underscores the specificity of PTPs and the importance of adaptor proteins in regulating PTP function in vivo. © 2017 Federation of European Biochemical Societies.

  2. Totally robot-assisted biliary pancreatic diversion with duodenal switch: single dock technique and technical outcomes.

    Science.gov (United States)

    Sudan, Ranjan; Podolsky, Erica

    2015-01-01

    The biliopancreatic diversion with duodenal switch (BPD/DS) requires operating in three different abdominal quadrants. Previous techniques have used either two docks or a hybrid technique in which the robot is used only to suture the duodeno-ileal anastomosis, while the rest of the operation was performed laparoscopically. Recently, a modification in technique has allowed all operative steps to be completed robotically with a single dock. The operative technique and its technical results are described. Operative technique is described. Baseline demographics, operative duration, length of stay, and adverse events (intraoperative, 30-days, and 1-year) of all primary totally robot BPD/DS cases are reported. From Nov. 2011 to Jan. 2014, 59 totally robotic BPD/DS operations were attempted. One was completed hybrid, and the rest were totally robotic. No robotic operation was converted to an open operation. Five trocars were placed, the small bowel was anchored to the anterior abdominal wall, and the robot was docked. Mean age was 44 ± 10 years with a mean preoperative BMI of 56 ± 9 kg/m(2). 69 % was female, and 71 % was Caucasian. Mean operative duration was 306 ± 80 min (60 min less than the hybrid technique). There were no mortality, leaks, venous thromboembolism, or bleeding requiring transfusion. Mean length of stay was 4.6 ± 4.3 days. Three patients were readmitted for nausea and vomiting. There was one superficial wound infection, and three patients needed reoperations in the first year, two for strictures, and one for debriding a suture abscess. All key technical components of the BPD/DS were performed with low morbidity and mortality with a single dock. Since the surgeon performed all key parts of the operation from the console, the need for experienced bedside assistance was minimized, resulting in shorter operative duration compared to the hybrid technique.

  3. Application of fuzzy logic-neural network based reinforcement learning to proximity and docking operations

    Science.gov (United States)

    Jani, Yashvant

    1992-01-01

    As part of the Research Institute for Computing and Information Systems (RICIS) activity, the reinforcement learning techniques developed at Ames Research Center are being applied to proximity and docking operations using the Shuttle and Solar Max satellite simulation. This activity is carried out in the software technology laboratory utilizing the Orbital Operations Simulator (OOS). This interim report provides the status of the project and outlines the future plans.

  4. Monte Carlo refinement of rigid-body protein docking structures with backbone displacement and side-chain optimization

    OpenAIRE

    Lorenzen, Stephan; Zhang, Yang

    2007-01-01

    Structures of hitherto unknown protein complexes can be predicted by docking the solved protein monomers. Here, we present a method to refine initial docking estimates of protein complex structures by a Monte Carlo approach including rigid-body moves and side-chain optimization. The energy function used is comprised of van der Waals, Coulomb, and atomic contact energy terms. During the simulation, we gradually shift from a novel smoothed van der Waals potential, which prevents trapping in loc...

  5. Medicinal plant phytochemicals and their inhibitory activities against pancreatic lipase: molecular docking combined with molecular dynamics simulation approach

    OpenAIRE

    Ahmed, Bilal; Ali Ashfaq, Usman; Mirza, Muhammad Usman

    2017-01-01

    Obesity is the worst health risk worldwide, which is linked to a number of diseases. Pancreatic lipase is considered as an affective cause of obesity and can be a major target for controlling the obesity. The present study was designed to find out best phytochemicals against pancreatic lipase through molecular docking combined with molecular dynamics (MD) simulation. For this purpose, a total of 3770 phytochemicals were docked against pancreatic lipase and ranked them on the basis of binding ...

  6. Docking and Molecular Dynamics Simulations in Potential Drugs Discovery: An Application to Influenza Virus M2 Protein

    OpenAIRE

    Bozdaganyan, Marine E.; Orekhov, Philipp S.; Bragazzi, Nicola L.; Eugeniya Pechkova; Roberto Gasparini; Claudio Nicolini

    2014-01-01

    Molecular docking is a common method for searching new potential drugs. Improvement of the results of docking can be achieved by different ways-one of them is molecular dynamics simulations of protein-ligand complexes. As a model for our research we chose M2 membrane protein from influenza virus. M2 protein is a high selective tetrameric pH-gated proton channel. It was previously shown that Omeprazole Family Compounds (OFC) block the "proton pump", though we hypothesized further tha...

  7. Multibody dynamical modeling for spacecraft docking process with spring-damper buffering device: A new validation approach

    Science.gov (United States)

    Daneshjou, Kamran; Alibakhshi, Reza

    2018-01-01

    In the current manuscript, the process of spacecraft docking, as one of the main risky operations in an on-orbit servicing mission, is modeled based on unconstrained multibody dynamics. The spring-damper buffering device is utilized here in the docking probe-cone system for micro-satellites. Owing to the impact occurs inevitably during docking process and the motion characteristics of multibody systems are remarkably affected by this phenomenon, a continuous contact force model needs to be considered. Spring-damper buffering device, keeping the spacecraft stable in an orbit when impact occurs, connects a base (cylinder) inserted in the chaser satellite and the end of docking probe. Furthermore, by considering a revolute joint equipped with torsional shock absorber, between base and chaser satellite, the docking probe can experience both translational and rotational motions simultaneously. Although spacecraft docking process accompanied by the buffering mechanisms may be modeled by constrained multibody dynamics, this paper deals with a simple and efficient formulation to eliminate the surplus generalized coordinates and solve the impact docking problem based on unconstrained Lagrangian mechanics. By an example problem, first, model verification is accomplished by comparing the computed results with those recently reported in the literature. Second, according to a new alternative validation approach, which is based on constrained multibody problem, the accuracy of presented model can be also evaluated. This proposed verification approach can be applied to indirectly solve the constrained multibody problems by minimum required effort. The time history of impact force, the influence of system flexibility and physical interaction between shock absorber and penetration depth caused by impact are the issues followed in this paper. Third, the MATLAB/SIMULINK multibody dynamic analysis software will be applied to build impact docking model to validate computed results and

  8. 33 CFR 165.504 - Newport News Shipbuilding and Dry Dock Company Shipyard, James River, Newport News, Va.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Newport News Shipbuilding and Dry... Coast Guard District § 165.504 Newport News Shipbuilding and Dry Dock Company Shipyard, James River... the Newport News Shipbuilding and Dry Dock Co. at latitude 37°00′38.1″ N, longitude 76°27′05.7″ W...

  9. The dock-and-coalesce mechanism for the association of a WASP disordered region with the Cdc42 GTPase.

    Science.gov (United States)

    Ou, Li; Matthews, Megan; Pang, Xiaodong; Zhou, Huan-Xiang

    2017-10-01

    Intrinsically disordered proteins (IDPs) play key roles in signaling and regulation. Many IDPs undergo folding upon binding to their targets. We have proposed that coupled folding and binding of IDPs generally follow a dock-and-coalesce mechanism, whereby a segment of the IDP, through diffusion, docks to its cognate subsite and, subsequently, the remaining segments coalesce around their subsites. Here, by a combination of experiment and computation, we determined the precise form of dock-and-coalesce operating in the association between the intrinsically disordered GTPase-binding domain (GBD) of the Wiskott-Aldrich Syndrome protein and the Cdc42 GTPase. The association rate constants (ka ) were measured by stopped-flow fluorescence under various solvent conditions. ka reached 10(7) m(-1) ·s(-1) at physiological ionic strength and had a strong salt dependence, suggesting that an electrostatically enhanced, diffusion-controlled docking step may be rate limiting. Our computation, based on the transient-complex theory, identified the N-terminal basic region of the GBD as the docking segment. However, several other changes in solvent conditions provided strong evidence that the coalescing step also contributed to determining the magnitude of ka . Addition of glucose and trifluoroethanol and an increase in temperature all produced experimental ka values much higher than expected from the effects on the docking rate alone. Conversely, addition of urea led to ka values much lower than expected if only the docking rate was affected. These results all pointed to ka being approximately two-thirds of the docking rate constant under physiological solvent conditions. © 2017 Federation of European Biochemical Societies.

  10. Message passing interface and multithreading hybrid for parallel molecular docking of large databases on petascale high performance computing machines.

    Science.gov (United States)

    Zhang, Xiaohua; Wong, Sergio E; Lightstone, Felice C

    2013-04-30

    A mixed parallel scheme that combines message passing interface (MPI) and multithreading was implemented in the AutoDock Vina molecular docking program. The resulting program, named VinaLC, was tested on the petascale high performance computing (HPC) machines at Lawrence Livermore National Laboratory. To exploit the typical cluster-type supercomputers, thousands of docking calculations were dispatched by the master process to run simultaneously on thousands of slave processes, where each docking calculation takes one slave process on one node, and within the node each docking calculation runs via multithreading on multiple CPU cores and shared memory. Input and output of the program and the data handling within the program were carefully designed to deal with large databases and ultimately achieve HPC on a large number of CPU cores. Parallel performance analysis of the VinaLC program shows that the code scales up to more than 15K CPUs with a very low overhead cost of 3.94%. One million flexible compound docking calculations took only 1.4 h to finish on about 15K CPUs. The docking accuracy of VinaLC has been validated against the DUD data set by the re-docking of X-ray ligands and an enrichment study, 64.4% of the top scoring poses have RMSD values under 2.0 Å. The program has been demonstrated to have good enrichment performance on 70% of the targets in the DUD data set. An analysis of the enrichment factors calculated at various percentages of the screening database indicates VinaLC has very good early recovery of actives. Copyright © 2013 Wiley Periodicals, Inc.

  11. Study on the interaction of Co (III) DiAmsar with serum albumins: Spectroscopic and molecular docking methods

    Science.gov (United States)

    Farahani, Bahman Vasheghani; Bardajee, Ghasem Rezanejade; Rajabi, Farzaneh Hosseinpour; Hooshyar, Zari

    2015-01-01

    This study was designed to examine the interaction of cobalt-3,6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane-1,8-diamine (Co(III) DiAmsar) as a hexadentate ligand with human serum albumin (HSA) and bovine serum albumin (BSA) under physiological conditions in Tris-HCl buffer solution at pH 7.4. To this aim, at first, Co (III) DiAmsar was synthesized and characterized by nuclear magnetic resonance (NMR), and mass spectroscopy and then its interaction with HSA and BSA was investigated by means of various spectroscopic methods (Fourier transform infrared (FT-IR), UV-visible (UV-vis), fluorescence, and cyclic voltammetry (CV)) and molecular docking technique. The results of fluorescence titration revealed that the Co (III) DiAmsar strongly quench the intrinsic fluorescence of HSA and BSA through a static quenching procedure. Binding constants (Ka) and the number of binding sites (n ∼ 1) were calculated using Stern-Volmer equations. The ΔG parameters at different temperatures were calculated. Subsequently, the values of ΔH and ΔS were also calculated, which revealed that the van der Waals and hydrogen bonding interaction splay a major role in Co (III) DiAmsar-HSA and Co (III) DiAmsar-BSA associations. The distance r between donor (HSA and BSA) and acceptor (Co (III) DiAmsar) was obtained according to fluorescence resonance energy transfer. The data obtained by the molecular modeling study revealed the surrounding residues of HSA and BSA around Co (III) DiAmsar.

  12. Integrated machine learning, molecular docking and 3D-QSAR based approach for identification of potential inhibitors of trypanosomal N-myristoyltransferase.

    Science.gov (United States)

    Singh, Nidhi; Shah, Priyanka; Dwivedi, Hemlata; Mishra, Shikha; Tripathi, Renu; Sahasrabuddhe, Amogh A; Siddiqi, Mohammad Imran

    2016-11-15

    N-Myristoyltransferase (NMT) catalyzes the transfer of myristate to the amino-terminal glycine of a subset of proteins, a co-translational modification involved in trafficking substrate proteins to membrane locations, stabilization and protein-protein interactions. It is a studied and validated pre-clinical drug target for fungal and parasitic infections. In the present study, a machine learning approach, docking studies and CoMFA analysis have been integrated with the objective of translation of knowledge into a pipelined workflow towards the identification of putative hits through the screening of large compound libraries. In the proposed pipeline, the reported parasitic NMT inhibitors have been used to develop predictive machine learning classification models. Simultaneously, a TbNMT complex model was generated to establish the relationship between the binding mode of the inhibitors for LmNMT and TbNMT through molecular dynamics simulation studies. A 3D-QSAR model was developed and used to predict the activity of the proposed hits in the subsequent step. The hits classified as active based on the machine learning model were assessed as the potential anti-trypanosomal NMT inhibitors through molecular docking studies, predicted activity using a QSAR model and visual inspection. In the final step, the proposed pipeline was validated through in vitro experiments. A total of seven hits have been proposed and tested in vitro for evaluation of dual inhibitory activity against Leishmania donovani and Trypanosoma brucei. Out of these five compounds showed significant inhibition against both of the organisms. The common topmost active compound SEW04173 belongs to a pyrazole carboxylate scaffold and is anticipated to enrich the chemical space with enhanced potency through optimization.

  13. Full-Scale System for Quantifying Leakage of Docking System Seals for Space Applications

    Science.gov (United States)

    Dunlap, Patrick H., Jr.; Daniels, Christopher C.; Steinetz, Bruce M.; Erker, Arthur H.; Robbie, Malcolm G.; Wasowski, Janice L.; Drlik, Gary J.; Tong, Michael T.; Penney, Nicholas

    2007-01-01

    NASA is developing a new docking and berthing system to support future space exploration missions to low-Earth orbit, the Moon, and Mars. This mechanism, called the Low Impact Docking System, is designed to connect pressurized space vehicles and structures. NASA Glenn Research Center is playing a key role in developing advanced technology for the main interface seal for this new docking system. The baseline system is designed to have a fully androgynous mating interface, thereby requiring a seal-on-seal configuration when two systems mate. These seals will be approximately 147 cm (58 in.) in diameter. NASA Glenn has designed and fabricated a new test fixture which will be used to evaluate the leakage of candidate full-scale seals under simulated thermal, vacuum, and engagement conditions. This includes testing under seal-on-seal or seal-on-plate configurations, temperatures from -50 to 50 C (-58 to 122 F), operational and pre-flight checkout pressure gradients, and vehicle misalignment (plus or minus 0.381 cm (0.150 in.)) and gapping (up to 0.10 cm (0.040 in.)) conditions. This paper describes the main design features of the test rig and techniques used to overcome some of the design challenges.

  14. Automated Rendezvous and Docking Sensor Testing at the Flight Robotics Laboratory

    Science.gov (United States)

    Howard, Richard T.; Williamson, Marlin L.; Johnston, Albert S.; Brewster, Linda L.; Mitchell, Jennifer D.; Cryan, Scott P.; Strack, David; Key, Kevin

    2007-01-01

    The Exploration Systems Architecture defines missions that require rendezvous, proximity operations, and docking (RPOD) of two spacecraft both in Low Earth Orbit (LEO) and in Low Lunar Orbit (LLO). Uncrewed spacecraft must perform automated and/or autonomous rendezvous, proximity operations and docking operations (commonly known as Automated Rendezvous and Docking, (AR&D).) The crewed versions of the spacecraft may also perform AR&D, possibly with a different level of automation and/or autonomy, and must also provide the crew with relative navigation information for manual piloting. The capabilities of the RPOD sensors are critical to the success of the Exploration Program. NASA has the responsibility to determine whether the Crew Exploration Vehicle (CEV) contractor-proposed relative navigation sensor suite will meet the CEV requirements. The relatively low technology readiness of relative navigation sensors for AR&D has been carried as one of the CEV Projects top risks. The AR&D Sensor Technology Project seeks to reduce this risk by increasing technology maturation of selected relative navigation sensor technologies through testing and simulation, and to allow the CEV Project to assess the relative navigation sensors.

  15. Structure-activity relationships and molecular docking of thirteen synthesized flavonoids as horseradish peroxidase inhibitors.

    Science.gov (United States)

    Mahfoudi, Reguia; Djeridane, Amar; Benarous, Khedidja; Gaydou, Emile M; Yousfi, Mohamed

    2017-10-01

    For the first time, the structure-activity relationships of thirteen synthesized flavonoids have been investigated by evaluating their ability to modulate horseradish peroxidase (HRP) catalytic activity. Indeed, a modified spectrophotometrically method was carried out and optimized using 4-methylcatechol (4-MC) as peroxidase co-substrate. The results show that these flavonoids exhibit a great capacity to inhibit peroxidase with Ki values ranged from 0.14±0.01 to 65±0.04mM. Molecular docking has been achieved using Auto Dock Vina program to discuss the nature of interactions and the mechanism of inhibition. According to the docking results, all the flavonoids have shown great binding affinity to peroxidase. These molecular modeling studies suggested that pyran-4-one cycle acts as an inhibition key for peroxidase. Therefore, potent peroxidase inhibitors are flavonoids with these structural requirements: the presence of the hydroxyl (OH) group in 7, 5 and 4' positions and the absence of the methoxy (O-CH3) group. Apigenin contributed better in HRP inhibitory activity. The present study has shown that the studied flavonoids could be promising HRP inhibitors, which can help in developing new molecules to control thyroid diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. 3D-QSAR and docking studies of flavonoids as potent Escherichia coli inhibitors

    Science.gov (United States)

    Fang, Yajing; Lu, Yulin; Zang, Xixi; Wu, Ting; Qi, XiaoJuan; Pan, Siyi; Xu, Xiaoyun

    2016-01-01

    Flavonoids are potential antibacterial agents. However, key substituents and mechanism for their antibacterial activity have not been fully investigated. The quantitative structure-activity relationship (QSAR) and molecular docking of flavonoids relating to potent anti-Escherichia coli agents were investigated. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were developed by using the pIC50 values of flavonoids. The cross-validated coefficient (q2) values for CoMFA (0.743) and for CoMSIA (0.708) were achieved, illustrating high predictive capabilities. Selected descriptors for the CoMFA model were ClogP (logarithm of the octanol/water partition coefficient), steric and electrostatic fields, while, ClogP, electrostatic and hydrogen bond donor fields were used for the CoMSIA model. Molecular docking results confirmed that half of the tested flavonoids inhibited DNA gyrase B (GyrB) by interacting with adenosine-triphosphate (ATP) pocket in a same orientation. Polymethoxyl flavones, flavonoid glycosides, isoflavonoids changed their orientation, resulting in a decrease of inhibitory activity. Moreover, docking results showed that 3-hydroxyl, 5-hydroxyl, 7-hydroxyl and 4-carbonyl groups were found to be crucial active substituents of flavonoids by interacting with key residues of GyrB, which were in agreement with the QSAR study results. These results provide valuable information for structure requirements of flavonoids as antibacterial agents. PMID:27049530

  17. Designing A Nonlinear Integer Programming Model For A Cross-Dock By A Genetic Algorithm

    Directory of Open Access Journals (Sweden)

    Bahareh Vaisi

    2015-03-01

    Full Text Available Abstract This paper presents a non-linear integer programming model for a cross-dock problem that considers the total transportation cost of inbound and outbound trucks from an origin to a destination and the total cost of assigning strip and stack doors to trucks based on their number of trips and the distance between doors in cross-dock. In previous studies these two cost-based problems are modeled separately however it is more realistic and practical to use both of them as an integrated cross-docking model. Additionally this model is solved for a randomly generated numerical example with three suppliers and two customers by the use of a genetic algorithm. By comparing two different parameter levels i.e. low and high numbers of populations the optimum solution is obtained considering a high level population size. A number of strip and stack doors are equal to a number of inbound and outbound trucks in the same sequence as 4 and 6 respectively. Finally the conclusion is presented.

  18. Aromatic interactions at the ligand-protein interface: Implications for the development of docking scoring functions.

    Science.gov (United States)

    Brylinski, Michal

    2018-02-01

    The ability to design and fine-tune non-covalent interactions between organic ligands and proteins is indispensable to rational drug development. Aromatic stacking has long been recognized as one of the key constituents of ligand-protein interfaces. In this communication, we employ a two-parameter geometric model to conduct a large-scale statistical analysis of aromatic contacts in the experimental and computer-generated structures of ligand-protein complexes, considering various combinations of aromatic amino acid residues and ligand rings. The geometry of interfacial π-π stacking in crystal structures accords with experimental and theoretical data collected for simple systems, such as the benzene dimer. Many contemporary ligand docking programs implicitly treat aromatic stacking with van der Waals and Coulombic potentials. Although this approach generally provides a sufficient specificity to model aromatic interactions, the geometry of π-π contacts in high-scoring docking conformations could still be improved. The comprehensive analysis of aromatic geometries at ligand-protein interfaces lies the foundation for the development of type-specific statistical potentials to more accurately describe aromatic interactions in molecular docking. A Perl script to detect and calculate the geometric parameters of aromatic interactions in ligand-protein complexes is available at https://github.com/michal-brylinski/earomatic. The dataset comprising experimental complex structures and computer-generated models is available at https://osf.io/rztha/. © 2017 John Wiley & Sons A/S.

  19. Fuzzy logic techniques for rendezvous and docking of two geostationary satellites

    Science.gov (United States)

    Ortega, Guillermo

    1995-01-01

    Large assemblings in space require the ability to manage rendezvous and docking operations. In future these techniques will be required for the gradual build up of big telecommunication platforms in the geostationary orbit. The paper discusses the use of fuzzy logic to model and implement a control system for the docking/berthing of two satellites in geostationary orbit. The system mounted in a chaser vehicle determines the actual state of both satellites and generates torques to execute maneuvers to establish the structural latching. The paper describes the proximity operations to collocate the two satellites in the same orbital window, the fuzzy guidance and navigation of the chaser approaching the target and the final Fuzzy berthing. The fuzzy logic system represents a knowledge based controller that realizes the close loop operations autonomously replacing the conventional control algorithms. The goal is to produce smooth control actions in the proximity of the target and during the docking to avoid disturbance torques in the final assembly orbit. The knowledge of the fuzzy controller consists of a data base of rules and the definitions of the fuzzy sets. The knowledge of an experienced spacecraft controller is captured into a set of rules forming the Rules Data Base.

  20. 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,

  1. Docking and molecular dynamics simulations of the ternary complex nisin2:lipid II

    Science.gov (United States)

    Mulholland, Sam; Turpin, Eleanor R.; Bonev, Boyan B.; Hirst, Jonathan D.

    2016-01-01

    Lanthionine antibiotics are an important class of naturally-occurring antimicrobial peptides. The best-known, nisin, is a commercial food preservative. However, structural and mechanistic details on nisin-lipid II membrane complexes are currently lacking. Recently, we have developed empirical force-field parameters to model lantibiotics. Docking and molecular dynamics (MD) simulations have been used to study the nisin2:lipid II complex in bacterial membranes, which has been put forward as the building block of nisin/lipid II binary membrane pores. An Ile1Trp mutation of the N-terminus of nisin has been modelled and docked onto lipid II models; the computed binding affinity increased compared to wild-type. Wild-type nisin was also docked onto three different lipid II structures and a stable 2:1 nisin:lipid II complex formed. This complex was inserted into a membrane. Six independent MD simulations revealed key interactions in the complex, specifically the N-terminal engagement of nisin with lipid II at the pyrophosphate and C-terminus of the pentapeptide chain. Nisin2 inserts into the membrane and we propose this as the first step in pore formation, mediated by the nisin N-terminus–lipid II pentapeptide hydrogen bond. The lipid II undecaprenyl chain adopted different conformations in the presence of nisin, which may also have implications for pore formation. PMID:26888784

  2. Imaging Flash Lidar for Safe Landing on Solar System Bodies and Spacecraft Rendezvous and Docking

    Science.gov (United States)

    Amzajerdian, Farzin; Roback, Vincent E.; Bulyshev, Alexander E.; Brewster, Paul F.; Carrion, William A; Pierrottet, Diego F.; Hines, Glenn D.; Petway, Larry B.; Barnes, Bruce W.; Noe, Anna M.

    2015-01-01

    NASA has been pursuing flash lidar technology for autonomous, safe landing on solar system bodies and for automated rendezvous and docking. During the final stages of the landing from about 1 kilometer to 500 meters above the ground, the flash lidar can generate 3-Dimensional images of the terrain to identify hazardous features such as craters, rocks, and steep slopes. The onboard flight computer can then use the 3-D map of terrain to guide the vehicle to a safe location. As an automated rendezvous and docking sensor, the flash lidar can provide relative range, velocity, and bearing from an approaching spacecraft to another spacecraft or a space station. NASA Langley Research Center has developed and demonstrated a flash lidar sensor system capable of generating 16,000 pixels range images with 7 centimeters precision, at 20 Hertz frame rate, from a maximum slant range of 1800 m from the target area. This paper describes the lidar instrument and presents the results of recent flight tests onboard a rocket-propelled free-flyer vehicle (Morpheus) built by NASA Johnson Space Center. The flights were conducted at a simulated lunar terrain site, consisting of realistic hazard features and designated landing areas, built at NASA Kennedy Space Center specifically for this demonstration test. This paper also provides an overview of the plan for continued advancement of the flash lidar technology aimed at enhancing its performance to meet both landing and automated rendezvous and docking applications.

  3. Docking studies on the binding of quinoline derivatives and hematin to Plasmodium falciparum lactate dehydrogenase.

    Science.gov (United States)

    Cortopassi, Wilian A; Oliveira, Aline A; Guimarães, Ana P; Rennó, Magdalena N; Krettli, Antoniana U; França, Tanos C C

    2011-08-01

    The literature has reported that ferriprotoporphyrin IX (hematin) intoxicates the malarial parasite through competition with NADH for the active site of the enzyme lactate dehydrogenase (LDH). In order to avoid this, the parasite polymerizes hematin to hemozoin. The quinoline derivatives are believed to form complexes with dimeric hematin, avoiding the formation of hemozoin and still inhibiting LDH. In order to investigate this hypothesis we calculated the docking energies of NADH and some quinoline derivatives (in the free forms and in complex with dimeric hematin) in the active site of the Plasmodium falciparum LDH (PfLDH). Ours results showed better docking score values to the complexes when compared to the free compounds, pointing them as more efficient inhibitors of Pf_LDH. Further we performed Molecular Dynamics (MD) simulations studies on the best docking conformation of the complex chloroquine-dimeric hematin with PfLDH. Our in silico results corroborate experimental data suggesting a possible action route for the quinoline derivatives in the inhibition of PfLDH.

  4. How to use not-always-reliable binding site information in protein-protein docking prediction.

    Science.gov (United States)

    Li, Lin; Huang, Yanzhao; Xiao, Yi

    2013-01-01

    In many protein-protein docking algorithms, binding site information is used to help predicting the protein complex structures. Using correct and accurate binding site information can increase protein-protein docking success rate significantly. On the other hand, using wrong binding sites information should lead to a failed prediction, or, at least decrease the success rate. Recently, various successful theoretical methods have been proposed to predict the binding sites of proteins. However, the predicted binding site information is not always reliable, sometimes wrong binding site information could be given. Hence there is a high risk to use the predicted binding site information in current docking algorithms. In this paper, a softly restricting method (SRM) is developed to solve this problem. By utilizing predicted binding site information in a proper way, the SRM algorithm is sensitive to the correct binding site information but insensitive to wrong information, which decreases the risk of using predicted binding site information. This SRM is tested on benchmark 3.0 using purely predicted binding site information. The result shows that when the predicted information is correct, SRM increases the success rate significantly; however, even if the predicted information is completely wrong, SRM only decreases success rate slightly, which indicates that the SRM is suitable for utilizing predicted binding site information.

  5. Binding of ethyl pyruvate to bovine serum albumin: Calorimetric, spectroscopic and molecular docking studies

    Energy Technology Data Exchange (ETDEWEB)

    Pathak, Mallika [Department of Chemistry, Miranda House, University of Delhi, Delhi 11007 (India); Mishra, Rashmi; Agarwala, Paban K. [Department of Radiation Genetics and Epigenetics, Division of Radioprotective Drug Development Research, Institute of Nuclear Medicine and Allied Sciences, Delhi 110054 (India); Ojha, Himanshu, E-mail: himanshu.drdo@gmail.com [Department of Radiation Genetics and Epigenetics, Division of Radioprotective Drug Development Research, Institute of Nuclear Medicine and Allied Sciences, Delhi 110054 (India); Singh, Bhawna [Department of Radiation Genetics and Epigenetics, Division of Radioprotective Drug Development Research, Institute of Nuclear Medicine and Allied Sciences, Delhi 110054 (India); Singh, Anju; Kukreti, Shrikant [Nucleic Acid Research Laboratory, Department of Chemistry, University of Delhi, Delhi 11007 (India)

    2016-06-10

    Highlights: • ITC study showed binding of ethyl pyruvate with BSA with high binding affinity. • Ethyl pyruvate binding caused conformation alteration of BSA. • Fluorescence quenching mechanism is static in nature. • Electrostatic, hydrogen bonding and hydrophobic forces involved in binding. • Docking confirmed role of electrostatic, hydrogen bonding and hydrophobic forces. - Abstract: Various in vitro and in vivo studies have shown the anti-inflammatory and anticancer potential role of ethyl pyruvate. Bio-distribution of drugs is significantly influenced by the drug-serum protein binding. Therefore, the binding mechanism of the ethyl pyruvate with bovine serum albumin was investigated using UV–vis absorption, fluorescence, circular dichroism, isothermal titration calorimetry and molecular docking techniques. Absorption and fluorescence quenching studies indicated the binding of ethyl pyruvate with protein. Circular dichroism spectra of bovine serum albumin confirmed significant change in the conformation of protein upon binding. Thermodynamic data confirmed that ethyl pyruvate binds to bovine serum albumin at the two different sites with high affinity. Binding of ethyl pyruvate to bovine serum albumin involves hydrogen bonding, van der Waal and hydrophobic interactions. Further, docking studies indicated that ethyl pyruvate could bind significantly at the three binding sites. The results will definitely contribute to the development of ethyl pyruvate as drug.

  6. Dynein light chain interaction with the peroxisomal import docking complex modulates peroxisome biogenesis in yeast.

    Science.gov (United States)

    Chang, Jinlan; Tower, Robert J; Lancaster, David L; Rachubinski, Richard A

    2013-10-15

    Dynein is a large macromolecular motor complex that moves cargo along microtubules. A motor-independent role for the light chain of dynein, Dyn2p, in peroxisome biology in Saccharomyces cerevisiae was suggested from its interaction with Pex14p, a component of the peroxisomal matrix protein import docking complex. Here we show that cells of the yeast Yarrowia lipolytica deleted for the gene encoding the homologue of Dyn2p are impaired in peroxisome function and biogenesis. These cells exhibit compromised growth on medium containing oleic acid as the carbon source, the metabolism of which requires functional peroxisomes. Their peroxisomes have abnormal morphology, atypical matrix protein localization, and an absence of proteolytic processing of the matrix enzyme thiolase, which normally occurs upon its import into the peroxisome. We also show physical and genetic interactions between Dyn2p and members of the docking complex, particularly Pex17p. Together, our results demonstrate a role for Dyn2p in the assembly of functional peroxisomes and provide evidence that Dyn2p acts in cooperation with the peroxisomal matrix protein import docking complex to effect optimal matrix protein import.

  7. HOMOLOGY MODELING AND DOCKING STUDIES OF HUMAN CHITOTRIOSIDASE WITH ITS NATURAL INHIBITORS

    Directory of Open Access Journals (Sweden)

    Deepsikha Roy

    2015-06-01

    Full Text Available Chitinase inhibitors have been found to have anti-inflammatory potential against asthma, allergic diseases and various other disorders. In this study various naturally occurring chitinase inhibitors against human chitinase (chitotriosidases, CHIT1 were studied with the help of protein-ligand docking. The structure of CHIT1 was modeled by homology modeling tool and validated with the help of various computational tools. Following validation, secondary structure, function and solvent accessibility of the protein was analyzed. A molecular dynamics (MD simulation study was conducted by GROMACS simulation package to study the stability of the structure. This was further followed by docking studies with natural inhibitors like allosamidin, argifin and argadin against CHIT1 by GLIDE docking software. Argadin was observed to have the highest affinity (G-score =-10.955 towards CHIT1 and allosamidin scored the lowest GLIDE score (G-score =-7.741. The structural behavior of the best inhibitor protein complex (CHIT1- argadin was validated through molecular dynamics simulation studies. A structure based virtual screening on the basis of the binding modes of these inhibitor was performed and best scoring hits were identified. The sequence analysis can be further used for the designing of potent drugs against diseases caused by CHIT1, thereby aiding knowledge in the field of research

  8. Effect of broad-leaved dock (Rumex obtusifolius L. on grass silage quality

    Directory of Open Access Journals (Sweden)

    Stanislav Hejduk

    2008-01-01

    Full Text Available The effect of broad-leaved dock (BLD on nutritive value and fermentation process of grassland fo­ra­ges was studied together with the effect of formic acid addition (4.0 vs. 2.0 l.t−1 and inoculation by lactic acid bacteria (LAB. Herbage of dock exhibits low DM content, crude protein and fibre contents, yet its NEL concentration is low.Despite of the low DM content in BLD silages, the fermentation process was successful, but the si­la­ges show significantly higher contents of lactic acid (176.5 %, acetic acid (198.2 % and lover pH va­lues (4.24 vs. 4.39 as compared with than the grass silage. Silages made of dock do not contain bu­ty­ric acid and exhibit low rates of proteolysis (9.2 % NH3 from total N. Addition of formic acid shows in the group of assessed silages significant reduction content of lactic acid (−6.5 % and acetic acid (−9.3 % and significant decrease of pH value (−0.05. The use of probiotic preparation leads to significantly higher lactic acid production (+39.3 % and to lover pH value (−0.23 as compare with control without additions.

  9. RIM determines Ca2+ channel density and vesicle docking at the presynaptic active zone

    Science.gov (United States)

    Han, Yunyun; Kaeser, Pascal S.; Südhof, Thomas C.; Schneggenburger, Ralf

    2012-01-01

    At presynaptic active zones, neurotransmitter release is initiated by the opening of voltage-gated Ca2+ channels close to docked vesicles. The mechanisms that enrich Ca2+ channels at active zones are, however, largely unknown, possibly because of the limited presynaptic accessibility of most synapses. Here, we have established a Cre-lox based conditional knock-out approach at a presynaptically accessible CNS synapse, the calyx of Held, to directly study the functions of RIM proteins. Removal of all RIM1/2 isoforms strongly reduced the presynaptic Ca2+ channel density, revealing a new role of RIM proteins in Ca2+ channel targeting. Removal of RIMs also reduced the readily-releasable pool, paralleled by a similar reduction of the number of docked vesicles, and the Ca2+ channel - vesicle coupling was decreased. Thus, RIM proteins co-ordinately regulate key functions for fast transmitter release: enabling a high presynaptic Ca2+ channel density, and vesicle docking at the active zone. PMID:21262468

  10. The ClusPro web server for protein-protein docking.

    Science.gov (United States)

    Kozakov, Dima; Hall, David R; Xia, Bing; Porter, Kathryn A; Padhorny, Dzmitry; Yueh, Christine; Beglov, Dmitri; Vajda, Sandor

    2017-02-01

    The ClusPro server (https://cluspro.org) is a widely used tool for protein-protein docking. The server provides a simple home page for basic use, requiring only two files in Protein Data Bank (PDB) format. However, ClusPro also offers a number of advanced options to modify the search; these include the removal of unstructured protein regions, application of attraction or repulsion, accounting for pairwise distance restraints, construction of homo-multimers, consideration of small-angle X-ray scattering (SAXS) data, and location of heparin-binding sites. Six different energy functions can be used, depending on the type of protein. Docking with each energy parameter set results in ten models defined by centers of highly populated clusters of low-energy docked structures. This protocol describes the use of the various options, the construction of auxiliary restraints files, the selection of the energy parameters, and the analysis of the results. Although the server is heavily used, runs are generally completed in <4 h.

  11. Customizable de novo design strategies for DOCK: Application to HIVgp41 and other therapeutic targets.

    Science.gov (United States)

    Allen, William J; Fochtman, Brian C; Balius, Trent E; Rizzo, Robert C

    2017-11-15

    De novo design can be used to explore vast areas of chemical space in computational lead discovery. As a complement to virtual screening, from-scratch construction of molecules is not limited to compounds in pre-existing vendor catalogs. Here, we present an iterative fragment growth method, integrated into the program DOCK, in which new molecules are built using rules for allowable connections based on known molecules. The method leverages DOCK's advanced scoring and pruning approaches and users can define very specific criteria in terms of properties or features to customize growth toward a particular region of chemical space. The code was validated using three increasingly difficult classes of calculations: (1) Rebuilding known X-ray ligands taken from 663 complexes using only their component parts (focused libraries), (2) construction of new ligands in 57 drug target sites using a library derived from ∼13M drug-like compounds (generic libraries), and (3) application to a challenging protein-protein interface on the viral drug target HIVgp41. The computational testing confirms that the de novo DOCK routines are robust and working as envisioned, and the compelling results highlight the potential utility for designing new molecules against a wide variety of important protein targets. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  12. Molecular docking and QSAR of aplyronine A and analogues: potent inhibitors of actin

    Science.gov (United States)

    Hussain, Abrar; Melville, James L.; Hirst, Jonathan D.

    2010-01-01

    Actin-binding natural products have been identified as a potential basis for the design of cancer therapeutic agents. We report flexible docking and QSAR studies on aplyronine A analogues. Our findings show the macrolide `tail' to be fundamental for the depolymerisation effect of actin-binding macrolides and that it is the tail which forms the initial interaction with the actin rather than the macrocycle, as previously believed. Docking energy scores for the compounds were highly correlated with actin depolymerisation activity. The 3D-QSAR models were predictive, with the best model giving a q 2 value of 0.85 and a r 2 of 0.94. Results from the docking simulations and the interpretation from QSAR "coeff*stdev" contour maps provide insight into the binding mechanism of each analogue and highlight key features that influence depolymerisation activity. The results herein may aid the design of a putative set of analogues that can help produce efficacious and tolerable anti-tumour agents. Finally, using the best QSAR model, we have also made genuine predictions for an independent set of recently reported aplyronine analogues.

  13. Why are most EU pigs tail docked? Economic and ethical analysis of four pig housing and management scenarios in the light of EU legislation and animal welfare outcomes.

    Science.gov (United States)

    D'Eath, R B; Niemi, J K; Vosough Ahmadi, B; Rutherford, K M D; Ison, S H; Turner, S P; Anker, H T; Jensen, T; Busch, M E; Jensen, K K; Lawrence, A B; Sandøe, P

    2016-04-01

    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 examining economic results of four management and housing scenarios, and by discussing their consequences for animal welfare in the light of legal and ethical considerations. The four scenarios compared are: 'Standard Docked', a conventional housing scenario with tail docking meeting the recommendations for Danish production (0.7 m2/pig); 'Standard Undocked', which is the same as 'Standard Docked' but with no tail docking, 'Efficient Undocked' and 'Enhanced Undocked', which have increased solid floor area (0.9 and 1.0 m2/pig, respectively) provision of loose manipulable materials (100 and 200 g/straw per pig per day) and no tail docking. A decision tree model based on data from Danish and Finnish pig production suggests that Standard Docked provides the highest economic gross margin with the least tail biting. Given our assumptions, Enhanced Undocked is the least economic, although Efficient Undocked is better economically and both result in a lower incidence of tail biting than Standard Undocked but higher than Standard Docked. For a pig, being bitten is worse for welfare (repeated pain, risk of infections) than being docked, but to compare welfare consequences at a farm level means considering the number of affected pigs. Because of the high levels of biting in Standard Undocked, it has on average inferior welfare to Standard Docked, whereas the comparison of Standard Docked and Enhanced (or Efficient) Undocked is more difficult. In Enhanced (or Efficient) Undocked, more pigs than in Standard Docked suffer from being tail bitten, whereas all the pigs avoid the acute pain of docking endured by the pigs in Standard Docked. We illustrate and discuss this ethical balance using

  14. 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.

  15. Semi-automted analysis of high-resolution aerial images to quantify docks in Upper Midwest glacial lakes

    Science.gov (United States)

    Beck, Marcus W.; Vondracek, Bruce C.; Hatch, Lorin K.; Vinje, Jason

    2013-01-01

    Lake resources can be negatively affected by environmental stressors originating from multiple sources and different spatial scales. Shoreline development, in particular, can negatively affect lake resources through decline in habitat quality, physical disturbance, and impacts on fisheries. The development of remote sensing techniques that efficiently characterize shoreline development in a regional context could greatly improve management approaches for protecting and restoring lake resources. The goal of this study was to develop an approach using high-resolution aerial photographs to quantify and assess docks as indicators of shoreline development. First, we describe a dock analysis workflow that can be used to quantify the spatial extent of docks using aerial images. Our approach incorporates pixel-based classifiers with object-based techniques to effectively analyze high-resolution digital imagery. Second, we apply the analysis workflow to quantify docks for 4261 lakes managed by the Minnesota Department of Natural Resources. Overall accuracy of the analysis results was 98.4% (87.7% based on ) after manual post-processing. The analysis workflow was also 74% more efficient than the time required for manual digitization of docks. These analyses have immediate relevance for resource planning in Minnesota, whereas the dock analysis workflow could be used to quantify shoreline development in other regions with comparable imagery. These data can also be used to better understand the effects of shoreline development on aquatic resources and to evaluate the effects of shoreline development relative to other stressors.

  16. Identifying the Enzymatic Mode of Action for Cellulase Enzymes by Means of Docking Calculations and a Machine Learning Algorithm

    Directory of Open Access Journals (Sweden)

    Somisetti V. Sambasivarao

    2014-01-01

    Full Text Available Docking calculations have been conducted on 36 cellulase enzymes and the results were evaluated by a machine learning algorithm to determine the nature of the enzyme (i.e. endo- or exo- enzymatic activity. The docking calculations have also been used to identify crucial substrate-enzyme interactions, and establish structure-function relationships. The use of carboxymethyl cellulose as a docking substrate is found to correctly identify the endo- or exo- behavior of cellulase enzymes with 92% accuracy while cellobiose docking calculations resulted in an 86% predictive accuracy. The binding distributions for cellobiose have been classified into two distinct types; distributions with a single maximum or distributions with a bi-modal structure. It is found that the uni-modal distributions correspond to exo- type enzyme while a bi-modal substrate docking distribution corresponds to endo- type enzyme. These results indicate that the use of docking calculations and machine learning algorithms are a fast and computationally inexpensive method for predicting if a cellulase enzyme possesses primarily endo- or exo- type behavior, while also revealing critical enzyme-substrate interactions.

  17. Tail docking in pigs: a review on its short- and long-term consequences and effectiveness in preventing tail biting

    Directory of Open Access Journals (Sweden)

    Eleonora Nannoni

    2014-02-01

    Full Text Available In spite of European legislation attempting to limit this practice, tail docking is nowadays the only preventive measure against tail biting which is widely adopted by farmers. Docking consists in amputating, usually without anaesthesia or analgesia, the distal part of the tail, in order to reduce its attractiveness and to sensitize it, increasing avoidance behaviour in the bitten pig. Tail docking results in both acute and chronic effects on pig welfare, and its effectiveness in preventing tail biting is limited, since it reduces the symptoms of a behavioural disorder, but does not address the underlying causes. The aim of the present paper is to review the available literature on the effects of tail docking on swine welfare. Although from a practical standpoint the welfare risks arising from tail docking may appear to be negligible compared to those arising during and after tail biting outbreaks, it should be considered that, apart from acute physiological and behavioural responses, tail docking may also elicit long-term effects on weight gain, tail stump sensitivity and animal freedom to express their normal behaviour. Such chronic effects have been poorly investigated so far. Besides, studies evaluating the effectiveness of anaesthetics or analgesic treatments are often conflicting. Within this framework, further research is recommended in order to reduce the acute and chronic pain and discomfort experienced by the animals, until preventive measures (e.g., environmental enrichment, stocking densities are broadly adopted to prevent tail biting.

  18. Lessons from (co-)evolution in the docking of proteins and peptides for CAPRI Rounds 28-35.

    Science.gov (United States)

    Yu, Jinchao; Andreani, Jessica; Ochsenbein, Françoise; Guerois, Raphaël

    2017-03-01

    Computational protein-protein docking is of great importance for understanding protein interactions at the structural level. Critical assessment of prediction of interactions (CAPRI) experiments provide the protein docking community with a unique opportunity to blindly test methods based on real-life cases and help accelerate methodology development. For CAPRI Rounds 28-35, we used an automatic docking pipeline integrating the coarse-grained co-evolution-based potential InterEvScore. This score was developed to exploit the information contained in the multiple sequence alignments of binding partners and selectively recognize co-evolved interfaces. Together with Zdock/Frodock for rigid-body docking, SOAP-PP for atomic potential and Rosetta applications for structural refinement, this pipeline reached high performance on a majority of targets. For protein-peptide docking and interfacial water position predictions, we also explored different means of taking evolutionary information into account. Overall, our group ranked 1 st by correctly predicting 10 targets, composed of 1 High, 7 Medium and 2 Acceptable predictions. Excellent and Outstanding levels of accuracy were reached for each of the two water prediction targets, respectively. Altogether, in 15 out of 18 targets in total, evolutionary information, either through co-evolution or conservation analyses, could provide key constraints to guide modeling towards the most likely assemblies. These results open promising perspectives regarding the way evolutionary information can be valuable to improve docking prediction accuracy. Proteins 2017; 85:378-390. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. An Elmo-Dock complex locally controls Rho GTPases and actin remodeling during cadherin-mediated adhesion.

    Science.gov (United States)

    Toret, Christopher P; Collins, Caitlin; Nelson, W James

    2014-12-08

    Cell-cell contact formation is a dynamic process requiring the coordination of cadherin-based cell-cell adhesion and integrin-based cell migration. A genome-wide RNA interference screen for proteins required specifically for cadherin-dependent cell-cell adhesion identified an Elmo-Dock complex. This was unexpected as Elmo-Dock complexes act downstream of integrin signaling as Rac guanine-nucleotide exchange factors. In this paper, we show that Elmo2 recruits Dock1 to initial cell-cell contacts in Madin-Darby canine kidney cells. At cell-cell contacts, both Elmo2 and Dock1 are essential for the rapid recruitment and spreading of E-cadherin, actin reorganization, localized Rac and Rho GTPase activities, and the development of strong cell-cell adhesion. Upon completion of cell-cell adhesion, Elmo2 and Dock1 no longer localize to cell-cell contacts and are not required subsequently for the maintenance of cell-cell adhesion. These studies show that Elmo-Dock complexes are involved in both integrin- and cadherin-based adhesions, which may help to coordinate the transition of cells from migration to strong cell-cell adhesion. © 2014 Toret et al.

  20. Waste Transfer Stations

    DEFF Research Database (Denmark)

    Christensen, Thomas Højlund

    2011-01-01

    tion and transport is usually the most costly part of any waste management system; and when waste is transported over a considerable distance or for a long time, transferring the waste from the collection vehicles to more efficient transportation may be economically beneficial. This involves...... a transfer station where the transfer takes place. These stations may also be accessible by private people, offering flexibility to the waste system, including facilities for bulky waste, household hazardous waste and recyclables. Waste transfer may also take place on the collection route from small...... describes the main features of waste transfer stations, including some considerations about the economical aspects on when transfer is advisable....

  1. Multi-Sensor Testing for Automated Rendezvous and Docking Sensor Testing at the Flight Robotics Laboratory

    Science.gov (United States)

    Brewster, L.; Johnston, A.; Howard, R.; Mitchell, J.; Cryan, S.

    2007-01-01

    The Exploration Systems Architecture defines missions that require rendezvous, proximity operations, and docking (RPOD) of two spacecraft both in Low Earth Orbit (LEO) and in Low Lunar Orbit (LLO). Uncrewed spacecraft must perform automated and/or autonomous rendezvous, proximity operations and docking operations (commonly known as AR&D). The crewed missions may also perform rendezvous and docking operations and may require different levels of automation and/or autonomy, and must provide the crew with relative navigation information for manual piloting. The capabilities of the RPOD sensors are critical to the success of the Exploration Program. NASA has the responsibility to determine whether the Crew Exploration Vehicle (CEV) contractor proposed relative navigation sensor suite will meet the requirements. The relatively low technology readiness level of AR&D relative navigation sensors has been carried as one of the CEV Project's top risks. The AR&D Sensor Technology Project seeks to reduce the risk by the testing and analysis of selected relative navigation sensor technologies through hardware-in-the-loop testing and simulation. These activities will provide the CEV Project information to assess the relative navigation sensors maturity as well as demonstrate test methods and capabilities. The first year of this project focused on a series of"pathfinder" testing tasks to develop the test plans, test facility requirements, trajectories, math model architecture, simulation platform, and processes that will be used to evaluate the Contractor-proposed sensors. Four candidate sensors were used in the first phase of the testing. The second phase of testing used four sensors simultaneously: two Marshall Space Flight Center (MSFC) Advanced Video Guidance Sensors (AVGS), a laser-based video sensor that uses retroreflectors attached to the target vehicle, and two commercial laser range finders. The multi-sensor testing was conducted at MSFC's Flight Robotics Laboratory (FRL

  2. Visual Sensory Signals Dominate Tactile Cues during Docked Feeding in Hummingbirds

    Directory of Open Access Journals (Sweden)

    Benjamin Goller

    2017-11-01

    Full Text Available Animals living in and interacting with natural environments must monitor and respond to changing conditions and unpredictable situations. Using information from multiple sensory systems allows them to modify their behavior in response to their dynamic environment but also creates the challenge of integrating different, and potentially contradictory, sources of information for behavior control. Understanding how multiple information streams are integrated to produce flexible and reliable behavior is key to understanding how behavior is controlled in natural settings. Natural settings are rarely still, which challenges animals that require precise body position control, like hummingbirds, which hover while feeding from flowers. Tactile feedback, available only once the hummingbird is docked at the flower, could provide additional information to help maintain its position at the flower. To investigate the role of tactile information for hovering control during feeding, we first asked whether hummingbirds physically interact with a feeder once docked. We quantified physical interactions between docked hummingbirds and a feeder placed in front of a stationary background pattern. Force sensors on the feeder measured a complex time course of loading that reflects the wingbeat frequency and bill movement of feeding hummingbirds, and suggests that they sometimes push against the feeder with their bill. Next, we asked whether the measured tactile interactions were used by feeding hummingbirds to maintain position relative to the feeder. We created two experimental scenarios—one in which the feeder was stationary and the visual background moved and the other where the feeder moved laterally in front of a white background. When the visual background pattern moved, docked hummingbirds pushed significantly harder in the direction of horizontal visual motion. When the feeder moved, and the background was stationary, hummingbirds generated aerodynamic force

  3. Synthesis, biological evaluation, QSAR analysis, and molecular docking of chalcone derivatives for antimalarial activity

    Directory of Open Access Journals (Sweden)

    Jufrizal Syahri

    2017-01-01

    Full Text Available Objective: To synthesize chalcone derivatives and investigate their antimalarial activity toward chloroquine-sensitive Plasmodium falciparum 3D7 (Pf3D7 strain; to develop quantitative structureactivity relationships (QSAR model to estimate IC50 values for biological activity of antimalarial and compared to experimental measurement; and to determine the binding interactions of the most active compounds with targeting P. falciparum dihydrofolate reductase-thymidylate synthase using molecular docking simulation. Methods: Seven chalcone derivatives have been synthesized from substituted acetophenone and substituted benzaldehyde in ethanol with the presence of bases catalysis at reflux condition. The QSAR analysis was conducted by using Gaussian 09 software to predict IC50 value for antimalarial activity. The in vitro test was evaluated against the chloroquine-sensitive Pf3D7 strain. Finally, the docking studies were performed with the CDOCKER protocol under the receptor-ligand interaction section in Discovery Studio® 3.1 (Accelrys, Inc., San Diego, USA. Results: Among the synthesized chalcone, a prenylated chalcone 5c and an allylated chalcones 10a showed the best IC 50 values of 1.08 and 1.73 μg/mL respectively against Pf3D7 strain (1.37 and 2.33 μg/mL based on QSAR analysis. Comparison between the prediction of IC50 value generated from the QSAR and the outcome from an in vitro assay showed a similar result as seen from the r2 value (r2 = 0.99. The most active compound 5c was employed in the docking simulation to determine the potential binding interactions with active sites of P. falciparum dihydrofolate reductase-thymidylate synthase (protein data bank ID: 1J3I. The docking simulation study showed 5c bind well with Ala16, Ser108, Ile164, Trp48, and Phe58 which are the crucial interactions that could possibly interrupt the sequential catalysis reactions in the thymidylate cycle and subsequently prevent deoxythymidine monophosphate production

  4. Study on the key technologies of the Transfer Equipment Cask for Tokamak Equator Port Plug

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Buyun, E-mail: ayun@iim.ac.cn [Department of Automation, University of Science and Technology of China, Hefei, Anhui 230027 (China); Robot Sensors and Human-Machine Interaction Laboratory, Institute of Intelligent Machines, Chinese Academy of Sciences, Hefei, Anhui 230031 (China); Gao, Lifu [Department of Automation, University of Science and Technology of China, Hefei, Anhui 230027 (China); Robot Sensors and Human-Machine Interaction Laboratory, Institute of Intelligent Machines, Chinese Academy of Sciences, Hefei, Anhui 230031 (China); Cao, Huibin; Sun, Jian [Robot Sensors and Human-Machine Interaction Laboratory, Institute of Intelligent Machines, Chinese Academy of Sciences, Hefei, Anhui 230031 (China); Sun, Yuxiang; Song, Quanjun; Ma, Chengxue; Chang, Li; Shuang, Feng [Department of Automation, University of Science and Technology of China, Hefei, Anhui 230027 (China); Robot Sensors and Human-Machine Interaction Laboratory, Institute of Intelligent Machines, Chinese Academy of Sciences, Hefei, Anhui 230031 (China)

    2014-12-15

    Highlights: • Design on Intelligent Air Transfer System (IATS) for Transfer Equipment Cask (TECA). • A rhombic-like parallel robot for docking with minimum misalignment. • Design on electro-hydraulic servo system of the TECA for Tokamak Equator Port Plug (TEPP) manipulation. • A control architecture with several algorithms and information acquired from sensors could be used by the TECA for Remote Handling (RH). - Abstract: The Transfer Equipment Cask (TECA) is a key solution for Remote Handling (RH) in Tokamak Equator Port Plug (TEPP) operations. From the perspectives of both engineering and technical designs of effective experiments on the TEPP, key technologies on these topics covering the TECA are required. According to conditions in ITER (International Thermonuclear Experimental Reactor) and features of the TEPP, this paper introduces the design of an Intelligent Air Transfer System (IATS) with an adaptive attitude and high precision positioning that transports a cask system of more than 30 tons from the Tokamak Building (TB) to the Hot Cell Building (HCB). Additionally, different actuators are discussed, and the hydraulic power drive is eventually selected and designed. A rhombic-like parallel robot is capable of being used for docking with minimum misalignment. Practical mechanisms of the cask system are presented for hostile environments. A control architecture with several algorithms and information acquired from sensors could be used by the TECA. These designs yield realistic and extended applications for the RH of ITER.

  5. Convective heat transfer

    CERN Document Server

    Kakac, Sadik; Pramuanjaroenkij, Anchasa

    2014-01-01

    Intended for readers who have taken a basic heat transfer course and have a basic knowledge of thermodynamics, heat transfer, fluid mechanics, and differential equations, Convective Heat Transfer, Third Edition provides an overview of phenomenological convective heat transfer. This book combines applications of engineering with the basic concepts of convection. It offers a clear and balanced presentation of essential topics using both traditional and numerical methods. The text addresses emerging science and technology matters, and highlights biomedical applications and energy technologies. What’s New in the Third Edition: Includes updated chapters and two new chapters on heat transfer in microchannels and heat transfer with nanofluids Expands problem sets and introduces new correlations and solved examples Provides more coverage of numerical/computer methods The third edition details the new research areas of heat transfer in microchannels and the enhancement of convective heat transfer with nanofluids....

  6. Introduction to heat transfer

    CERN Document Server

    SUNDÉN, B

    2012-01-01

    Presenting the basic mechanisms for transfer of heat, Introduction to Heat Transfer gives a deeper and more comprehensive view than existing titles on the subject. Derivation and presentation of analytical and empirical methods are provided for calculation of heat transfer rates and temperature fields as well as pressure drop. The book covers thermal conduction, forced and natural laminar and turbulent convective heat transfer, thermal radiation including participating media, condensation, evaporation and heat exchangers.

  7. Impact of transmammary-delivered meloxicam on biomarkers of pain and distress in piglets after castration and tail docking.

    Science.gov (United States)

    Bates, Jessica L; Karriker, Locke A; Stock, Matthew L; Pertzborn, Kelly M; Baldwin, Luke G; Wulf, Larry W; Lee, C J; Wang, Chong; Coetzee, Johann F

    2014-01-01

    To investigate a novel route for providing analgesia to processed piglets via transmammary drug delivery, meloxicam was administered orally to sows after farrowing. The objectives of the study were to demonstrate meloxicam transfer from sows to piglets via milk and to describe the analgesic effects in piglets after processing through assessment of pain biomarkers and infrared thermography (IRT). Ten sows received either meloxicam (30 mg/kg) (n = 5) or whey protein (placebo) (n = 5) in their daily feedings, starting four days after farrowing and continuing for three consecutive days. During this period, blood and milk samples were collected at 12-hour intervals. On Day 5 after farrowing, three boars and three gilts from each litter were castrated or sham castrated, tail docked, and administered an iron injection. Piglet blood samples were collected immediately before processing and at predetermined times over an 84-hour period. IRT images were captured at each piglet blood collection point. Plasma was tested to confirm meloxicam concentrations using a validated high-performance liquid chromatography-mass spectrometry method. Meloxicam was detected in all piglets nursing on medicated sows at each time point, and the mean (± standard error of the mean) meloxicam concentration at castration was 568.9±105.8 ng/mL. Furthermore, ex-vivo prostaglandin E2 (PGE2) synthesis inhibition was greater in piglets from treated sows compared to controls (p = 0.0059). There was a time-by-treatment interaction for plasma cortisol (p = 0.0009), with meloxicam-treated piglets demonstrating lower cortisol concentrations than control piglets for 10 hours after castration. No differences in mean plasma substance P concentrations between treatment groups were observed (p = 0.67). Lower cranial skin temperatures on IRT were observed in placebo compared to meloxicam-treated piglets (p = 0.015). This study demonstrates the successful transfer of meloxicam from sows to

  8. Impact of transmammary-delivered meloxicam on biomarkers of pain and distress in piglets after castration and tail docking.

    Directory of Open Access Journals (Sweden)

    Jessica L Bates

    Full Text Available To investigate a novel route for providing analgesia to processed piglets via transmammary drug delivery, meloxicam was administered orally to sows after farrowing. The objectives of the study were to demonstrate meloxicam transfer from sows to piglets via milk and to describe the analgesic effects in piglets after processing through assessment of pain biomarkers and infrared thermography (IRT. Ten sows received either meloxicam (30 mg/kg (n = 5 or whey protein (placebo (n = 5 in their daily feedings, starting four days after farrowing and continuing for three consecutive days. During this period, blood and milk samples were collected at 12-hour intervals. On Day 5 after farrowing, three boars and three gilts from each litter were castrated or sham castrated, tail docked, and administered an iron injection. Piglet blood samples were collected immediately before processing and at predetermined times over an 84-hour period. IRT images were captured at each piglet blood collection point. Plasma was tested to confirm meloxicam concentrations using a validated high-performance liquid chromatography-mass spectrometry method. Meloxicam was detected in all piglets nursing on medicated sows at each time point, and the mean (± standard error of the mean meloxicam concentration at castration was 568.9±105.8 ng/mL. Furthermore, ex-vivo prostaglandin E2 (PGE2 synthesis inhibition was greater in piglets from treated sows compared to controls (p = 0.0059. There was a time-by-treatment interaction for plasma cortisol (p = 0.0009, with meloxicam-treated piglets demonstrating lower cortisol concentrations than control piglets for 10 hours after castration. No differences in mean plasma substance P concentrations between treatment groups were observed (p = 0.67. Lower cranial skin temperatures on IRT were observed in placebo compared to meloxicam-treated piglets (p = 0.015. This study demonstrates the successful transfer of meloxicam from

  9. Transfer of gaming

    NARCIS (Netherlands)

    Korteling, J.E.

    2012-01-01

    An overview is provided of the activities and results op GATE WP 4.4 entiteld Transfer of Gaming (ToG). This work package has produced the principles and methodologies concerning optimalization and measurement of transfer of training in serious gaming. In addition, true transfer of job-specific

  10. Intramolecular Energy Transfer, Charge Transfer & Hydrogen Bond

    Indian Academy of Sciences (India)

    Ultrafast Dynamics of Chemical Reactions in Condensed Phase: Intramolecular Energy Transfer, Charge Transfer & Hydrogen Bond · PowerPoint Presentation · Slide 3 · Slide 4 · Slide 5 · Slide 6 · Slide 7 · Slide 8 · Slide 9 · Slide 10 · Slide 11 · Slide 12 · Slide 13 · Slide 14 · Slide 15 · Slide 16 · Slide 17 · Slide 18 · Slide 19.

  11. Making benefit transfers work

    DEFF Research Database (Denmark)

    Bateman, I. J.; Brouwer, R.; Ferrini, S.

    2011-01-01

    We develop and test guidance principles for benefits transfers. These argue that when transferring across relatively similar sites, simple mean value transfers are to be preferred but that when sites are relatively dissimilar then value function transfers will yield lower errors. The paper also...... provides guidance on the appropriate specification of transferable value functions arguing that these should be developed from theoretical rather than ad-hoc statistical principles. These principles are tested via a common format valuation study of water quality improvements across five countries. Results...

  12. Making benefit transfers work

    DEFF Research Database (Denmark)

    Bateman, I.J.; Brouwer, R.; Ferrini, S.

    We develop and test guidance principles for benefits transfers. These argue that when transferring across relatively similar sites, simple mean value transfers are to be preferred but that when sites are relatively dissimilar then value function transfers will yield lower errors. The paper also...... provides guidance on the appropriate specification of transferable value functions arguing that these should be developed from theoretical rather than ad-hoc statistical principles. These principles are tested via a common format valuation study of water quality improvements across five countries. Results...

  13. Electron transfer reactions

    CERN Document Server

    Cannon, R D

    2013-01-01

    Electron Transfer Reactions deals with the mechanisms of electron transfer reactions between metal ions in solution, as well as the electron exchange between atoms or molecules in either the gaseous or solid state. The book is divided into three parts. Part 1 covers the electron transfer between atoms and molecules in the gas state. Part 2 tackles the reaction paths of oxidation states and binuclear intermediates, as well as the mechanisms of electron transfer. Part 3 discusses the theories and models of the electron transfer process; theories and experiments involving bridged electron transfe

  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. Design of Novel Chemotherapeutic Agents Targeting Checkpoint Kinase 1 Using 3D-QSAR Modeling and Molecular Docking Methods.

    Science.gov (United States)

    Balupuri, Anand; Balasubramanian, Pavithra K; Cho, Seung J

    2016-01-01

    Checkpoint kinase 1 (Chk1) has emerged as a potential therapeutic target for design and development of novel anticancer drugs. Herein, we have performed three-dimensional quantitative structure-activity relationship (3D-QSAR) and molecular docking analyses on a series of diazacarbazoles to design potent Chk1 inhibitors. 3D-QSAR models were developed using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) techniques. Docking studies were performed using AutoDock. The best CoMFA and CoMSIA models exhibited cross-validated correlation coefficient (q2) values of 0.631 and 0.585, and non-cross-validated correlation coefficient (r2) values of 0.933 and 0.900, respectively. CoMFA and CoMSIA models showed reasonable external predictabilities (r2 pred) of 0.672 and 0.513, respectively. A satisfactory performance in the various internal and external validation techniques indicated the reliability and robustness of the best model. Docking studies were performed to explore the binding mode of inhibitors inside the active site of Chk1. Molecular docking revealed that hydrogen bond interactions with Lys38, Glu85 and Cys87 are essential for Chk1 inhibitory activity. The binding interaction patterns observed during docking studies were complementary to 3D-QSAR results. Information obtained from the contour map analysis was utilized to design novel potent Chk1 inhibitors. Their activities and binding affinities were predicted using the derived model and docking studies. Designed inhibitors were proposed as potential candidates for experimental synthesis.

  17. DOCK1 inhibition suppresses cancer cell invasion and macropinocytosis induced by self-activating Rac1P29Smutation.

    Science.gov (United States)

    Tomino, Takahiro; Tajiri, Hirotada; Tatsuguchi, Takaaki; Shirai, Takahiro; Oisaki, Kounosuke; Matsunaga, Shigeki; Sanematsu, Fumiyuki; Sakata, Daiji; Yoshizumi, Tomoharu; Maehara, Yoshihiko; Kanai, Motomu; Cote, Jean-François; Fukui, Yoshinori; Uruno, Takehito

    2018-02-09

    Rac1 is a member of the Rho family of small GTPases that regulates cytoskeletal reorganization, membrane polarization, cell migration and proliferation. Recently, a self-activating mutation of Rac1, Rac1 P29S , has been identified as a recurrent somatic mutation frequently found in sun-exposed melanomas, which possesses increased inherent GDP/GTP exchange activity and cell transforming ability. However, the role of cellular Rac1-interacting proteins in the transforming potential of Rac1 P29S remains unclear. We found that the catalytic domain of DOCK1, a Rac-specific guanine nucleotide exchange factor (GEF) implicated in malignancy of a variety of cancers, can greatly accelerate the GDP/GTP exchange of Rac1 P29S . Enforced expression of Rac1 P29S induced matrix invasion and macropinocytosis in wild-type (WT) mouse embryonic fibroblasts (MEFs), but not in DOCK1-deficient MEFs. Consistently, a selective inhibitor of DOCK1 that blocks its GEF function suppressed the invasion and macropinocytosis in WT MEFs expressing Rac1 P29S . Human melanoma IGR-1 and breast cancer MDA-MB-157 cells harbor Rac1 P29S mutation and express DOCK1 endogenously. Genetic inactivation and pharmacological inhibition of DOCK1 suppressed their invasion and macropinocytosis. Taken together, these results indicate that DOCK1 is a critical regulator of the malignant phenotypes induced by Rac1 P29S , and suggest that targeting DOCK1 might be an effective approach to treat cancers associated with Rac1 P29S mutation. Copyright © 2018. Published by Elsevier Inc.

  18. Pulsed electron paramagnetic resonance study of domain docking in neuronal nitric oxide synthase: the calmodulin and output state perspective.

    Science.gov (United States)

    Astashkin, Andrei V; Chen, Li; Zhou, Xixi; Li, Huiying; Poulos, Thomas L; Liu, Ke Jian; Guillemette, J Guy; Feng, Changjian

    2014-08-28

    The binding of calmodulin (CaM) to neuronal nitric oxide synthase (nNOS) enables formation of the output state of nNOS for nitric oxide production. Essential to NOS function is the geometry and dynamics of CaM docking to the NOS oxygenase domain, but little is known about these details. In the present work, the domain docking in a CaM-bound oxygenase/FMN (oxyFMN) construct of nNOS was investigated using the relaxation-induced dipolar modulation enhancement (RIDME) technique, which is a pulsed electron paramagnetic resonance technique sensitive to the magnetic dipole interaction between the electron spins. A cysteine was introduced at position 110 of CaM, after which a nitroxide spin label was attached at the position. The RIDME study of the magnetic dipole interaction between the spin label and the ferric heme centers in the oxygenase domain of nNOS revealed that, with increasing [Ca(2+)], the concentration of nNOS·CaM complexes increases and reaches a maximum at [Ca(2+)]/[CaM] ≥ 4. The RIDME kinetics of CaM-bound nNOS represented monotonous decays without well-defined oscillations. The analysis of these kinetics based on the structural models for the open and docked states has shown that only about 15 ± 3% of the CaM-bound nNOS is in the docked state at any given time, while the remaining 85 ± 3% of the protein is in the open conformations characterized by a wide distribution of distances between the bound CaM and the oxygenase domain. The results of this investigation are consistent with a model that the Ca(2+)-CaM interaction causes CaM docking with the oxygenase domain. The low population of the docked state indicates that the CaM-controlled docking between the FMN and heme domains is highly dynamic.

  19. Transfer function combinations

    KAUST Repository

    Zhou, Liang

    2012-10-01

    Direct volume rendering has been an active area of research for over two decades. Transfer function design remains a difficult task since current methods, such as traditional 1D and 2D transfer functions, are not always effective for all data sets. Various 1D or 2D transfer function spaces have been proposed to improve classification exploiting different aspects, such as using the gradient magnitude for boundary location and statistical, occlusion, or size metrics. In this paper, we present a novel transfer function method which can provide more specificity for data classification by combining different transfer function spaces. In this work, a 2D transfer function can be combined with 1D transfer functions which improve the classification. Specifically, we use the traditional 2D scalar/gradient magnitude, 2D statistical, and 2D occlusion spectrum transfer functions and combine these with occlusion and/or size-based transfer functions to provide better specificity. We demonstrate the usefulness of the new method by comparing to the following previous techniques: 2D gradient magnitude, 2D occlusion spectrum, 2D statistical transfer functions and 2D size based transfer functions. © 2012 Elsevier Ltd.

  20. Deletion of Dock10 in B Cells Results in Normal Development but a Mild Deficiency upon In Vivo and In Vitro Stimulations

    Directory of Open Access Journals (Sweden)

    Eva Severinson

    2017-05-01

    Full Text Available We sought to identify genes necessary to induce cytoskeletal change in B cells. Using gene expression microarray, we compared B cells stimulated with interleukin-4 (IL-4 and anti-CD40 antibodies that induce B cell spreading, cell motility, tight aggregates, and extensive microvilli with B cells stimulated with lipopolysaccharide that lack these cytoskeletal changes. We identified 84 genes with 10-fold or greater expression in anti-CD40 + IL-4 stimulated B cells, one of these encoded the guanine nucleotide exchange factor (GEF dedicator of cytokinesis 10 (Dock10. IL-4 selectively induced Dock10 expression in B cells. Using lacZ expression to monitor Dock10 promoter activity, we found that Dock10 was expressed at all stages during B cell development. However, specific deletion of Dock10 in B cells was associated with a mild phenotype with normal B cell development and normal B cell spreading, polarization, motility, chemotaxis, aggregation, and Ig class switching. Dock10-deficient B cells showed lower proliferation in response to anti-CD40 and IL-4 stimulation. Moreover, the IgG response to soluble antigen in vivo was lower when Dock10 was specifically deleted in B cells. Together, we found that most B cell responses were intact in the absence of Dock10. However, specific deletion of Dock10 in B cells was associated with a mild reduction in B cell activation in vitro and in vivo.