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Sample records for bioactive molecular conformational

  1. Cyndi: a multi-objective evolution algorithm based method for bioactive molecular conformational generation

    Directory of Open Access Journals (Sweden)

    Li Honglin

    2009-03-01

    Full Text Available Abstract Background Conformation generation is a ubiquitous problem in molecule modelling. Many applications require sampling the broad molecular conformational space or perceiving the bioactive conformers to ensure success. Numerous in silico methods have been proposed in an attempt to resolve the problem, ranging from deterministic to non-deterministic and systemic to stochastic ones. In this work, we described an efficient conformation sampling method named Cyndi, which is based on multi-objective evolution algorithm. Results The conformational perturbation is subjected to evolutionary operation on the genome encoded with dihedral torsions. Various objectives are designated to render the generated Pareto optimal conformers to be energy-favoured as well as evenly scattered across the conformational space. An optional objective concerning the degree of molecular extension is added to achieve geometrically extended or compact conformations which have been observed to impact the molecular bioactivity (J Comput -Aided Mol Des 2002, 16: 105–112. Testing the performance of Cyndi against a test set consisting of 329 small molecules reveals an average minimum RMSD of 0.864 Å to corresponding bioactive conformations, indicating Cyndi is highly competitive against other conformation generation methods. Meanwhile, the high-speed performance (0.49 ± 0.18 seconds per molecule renders Cyndi to be a practical toolkit for conformational database preparation and facilitates subsequent pharmacophore mapping or rigid docking. The copy of precompiled executable of Cyndi and the test set molecules in mol2 format are accessible in Additional file 1. Conclusion On the basis of MOEA algorithm, we present a new, highly efficient conformation generation method, Cyndi, and report the results of validation and performance studies comparing with other four methods. The results reveal that Cyndi is capable of generating geometrically diverse conformers and outperforms

  2. Molecular field technology applied to virtual screening and finding the bioactive conformation.

    Science.gov (United States)

    Cheeseright, Tim; Mackey Phd, Mark; Rose Phd, Sally; Vinter Phd, Andy

    2007-01-01

    Virtual screening is being applied to reduce the high-throughput screening bottleneck in many pharmaceutical companies and to reduce compound wastage. Cresset's ligand-based virtual screening technology using molecular fields can facilitate rapid identification of novel chemotypes from biologically testing only 200 - 1000 compounds. Four molecular fields calculated using the interaction of different probe atoms with the ligand are sufficient to describe how a ligand binds to its protein. Compounds with similar fields to known active ligands are predicted to have a high probability of showing similar activity. As binding is related to field similarity, this property has been exploited further to predict the bioactive conformation of small sets of structurally diverse active ligands starting from the two-dimensional structures alone without knowledge of the target site structure.

  3. Recent Advances in the Study of the Bioactive Conformation of Taxol

    OpenAIRE

    Sun, Liang; Simmerling, Carlos; Ojima, Iwao

    2009-01-01

    Paclitaxel is one of the most important chemotherapeutic drugs in the fight against cancer. This minireview covers the recent advances in the study of the bioactive conformation of paclitaxel in tubulin/microtubules. The tubulin-bound structure of paclitaxel has been studied by means of photoaffinity labeling, cryo-electron microscopy, solid-state NMR, molecular modeling, MD simulations and the synthesis of conformationally restrained analogues and paclitaxel mimics. The bioactive conformatio...

  4. Attachment and conformational changes of collagen on bioactive glass surface.

    Science.gov (United States)

    Magyari, K; Vanea, E; Baia, L; Simon, V

    2016-05-12

    The proteins adsorption on biomaterials surface leads to changes in their structural conformation that may further influence the adhesion, migration and growth of cells. The aim of this study was to examine the attachment of collagen (calf skin type I) on bioactive glass powders and the conformational changes of the protein. Scanning electron microscopy analysis and X-ray photoelectron spectroscopy measurements indicate that the collagen cover the glass surface in a nanometric thin layer. The infrared amide I absorption signal shows pronounced changes in the secondary structure of the adsorbed collagen. PMID:27175468

  5. Synthesis and Bioactivity of a Side Chain Bridged Paclitaxel: A Test of the T-Taxol Conformation

    OpenAIRE

    Hodge, Mathis; Chen, Qiao-Hong; Bane, Susan; Sharma, Shubhada; Loew, Maura; Banerjee, Abhijit; Alcaraz, Ana A.; Snyder, James P.; Kingston, David G I

    2009-01-01

    A knowledge of the bioactive tubulin-binding conformation of paclitaxel (Taxol™) is crucial to a full understanding of the bioactivity of this important anticancer drug, and potentially also to the design of simplified analogs. The bioactive conformation has been shown to be best approximated by the T-Taxol conformation. As a further test of this conclusion, the paclitaxel analog 4 was designed as a compound which has all the chemical functionality necessary for activity, but which cannot ado...

  6. Synthesis and bioactivity of a side chain bridged paclitaxel: A test of the T-Taxol conformation.

    Science.gov (United States)

    Hodge, Mathis; Chen, Qiao-Hong; Bane, Susan; Sharma, Shubhada; Loew, Maura; Banerjee, Abhijit; Alcaraz, Ana A; Snyder, James P; Kingston, David G I

    2009-05-15

    A knowledge of the bioactive tubulin-binding conformation of paclitaxel (Taxol()) is crucial to a full understanding of the bioactivity of this important anticancer drug, and potentially also to the design of simplified analogs. The bioactive conformation has been shown to be best approximated by the T-Taxol conformation. As a further test of this conclusion, the paclitaxel analog 4 was designed as a compound which has all the chemical functionality necessary for activity, but which cannot adopt the T-Taxol conformation. The synthesis and bioassay of 4 confirmed its lack of activity, and thus provided further support for the T-Taxol conformation as the bioactive tubulin-binding conformation.

  7. Spatial separation of molecular conformers and clusters.

    Science.gov (United States)

    Horke, Daniel; Trippel, Sebastian; Chang, Yuan-Pin; Stern, Stephan; Mullins, Terry; Kierspel, Thomas; Küpper, Jochen

    2014-01-09

    Gas-phase molecular physics and physical chemistry experiments commonly use supersonic expansions through pulsed valves for the production of cold molecular beams. However, these beams often contain multiple conformers and clusters, even at low rotational temperatures. We present an experimental methodology that allows the spatial separation of these constituent parts of a molecular beam expansion. Using an electric deflector the beam is separated by its mass-to-dipole moment ratio, analogous to a bender or an electric sector mass spectrometer spatially dispersing charged molecules on the basis of their mass-to-charge ratio. This deflector exploits the Stark effect in an inhomogeneous electric field and allows the separation of individual species of polar neutral molecules and clusters. It furthermore allows the selection of the coldest part of a molecular beam, as low-energy rotational quantum states generally experience the largest deflection. Different structural isomers (conformers) of a species can be separated due to the different arrangement of functional groups, which leads to distinct dipole moments. These are exploited by the electrostatic deflector for the production of a conformationally pure sample from a molecular beam. Similarly, specific cluster stoichiometries can be selected, as the mass and dipole moment of a given cluster depends on the degree of solvation around the parent molecule. This allows experiments on specific cluster sizes and structures, enabling the systematic study of solvation of neutral molecules.

  8. Design and synthesis of de novo cytotoxic alkaloids by mimicking the bioactive conformation of paclitaxel

    OpenAIRE

    Sun, Liang; Veith, Jean M.; Pera, Paula; Bernacki, Ralph J.; Ojima, Iwao

    2010-01-01

    Novel paclitaxel-mimicking alkaloids were designed and synthesized based on a bioactive conformation of paclitaxel, i.e., REDOR-Taxol. The alkaloid 2 bearing a 5-7-6 tricyclic scaffold mimics REDOR-Taxol best among the compounds designed and was found to be the most potent compound against several drug-sensitive and drug-resistant human cancer cell lines. MD simulation study on the paclitaxel mimics 1 and 2 as well as REDOR-Taxol bound to the 1JFF tubulin structure was quite informative to ev...

  9. Conformation effects on the molecular orbitals of serine

    Institute of Scientific and Technical Information of China (English)

    Wang Ke-Dong; Ma Peng-Fei; Shan Xu

    2011-01-01

    This paper calculates the five most stable conformers of serine with Hartree-Fock theory, density functional theory (B3LYP), M0ller-Plesset perturbation theory (MP4(SDQ)) and electron propagation theory with the 6-311++G(2d,2p) basis set. The calculated vertical ionization energies for the valence molecular orbitals of each conformer are in agreement with the experimental data, indicating that a range of molecular conformations would coexist in an equilibrium sample. Information of the five outer valence molecular orbitals for each conformer is explored in coordinate and momentum spaces using dual space analysis to investigate the conformational processes, which are generated from the global minimum conformer Serl by rotation of C2-C3 (Ser4), C1-C2 (Ser5) and C1-O2 (Ser2 and Ser3). Orbitals 28a, 27a and 26a are identified as the fingerprint orbitals for all the conformational processes.

  10. On the stochastic dynamics of molecular conformation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    An important functioning mechanism of biological macromolecules is the transition between different conformed states due to thermal fluctuation. In the present paper, a biological macromolecule is modeled as two strands with side chains facing each other, and its stochastic dynamics including the statistics of stationary motion and the statistics of conformational transition is studied by using the stochastic averaging method for quasi Hamiltonian systems. The theoretical results are confirmed with the results from Monte Carlo simulation.

  11. Cembrene Diterpenoids: Conformational Studies and Molecular Docking to Tubulin

    Directory of Open Access Journals (Sweden)

    Heather E. Villanueva

    2010-04-01

    Full Text Available A conformational analysis of the cembrene diterpenoids cembrene, cembrene A, (3Z-cembrene A, isocembrene, casbene, and incensole, has been carried out using density functional theory at the B3LYP/6-31G* level of theory. A molecular docking analysis of these cembrenoids with tubulin has also been performed in order to assess the potential of tubulin binding of these cytotoxic agents. The macrocyclic cembrenoids are conformationally mobile and numerous low-energy conformations were found. Molecular docking reveals that the cembrenoids dock into the colchicine binding site of tubulin with comparable docking energies to colchicine.

  12. The bound conformation of microtubule-stabilizing agents: NMR insights into the bioactive 3D structure of discodermolide and dictyostatin.

    Science.gov (United States)

    Canales, Angeles; Matesanz, Ruth; Gardner, Nicola M; Andreu, José Manuel; Paterson, Ian; Díaz, J Fernando; Jiménez-Barbero, Jesús

    2008-01-01

    A protocol based on a combination of NMR experimental data with molecular mechanics calculations and docking procedures has been employed to determine the microtubule-bound conformation of two microtubule-stabilizing agents, discodermolide (DDM) and dictyostatin (DCT). The data indicate that tubulin in assembled microtubules recognizes DDM through a conformational selection process, with minor changes in the molecular skeleton between the major conformer in water solution and that bound to assembled microtubules. For DCT, the deduced bound geometry presents some key conformation differences around certain torsion angles, with respect to the major conformer in solution, and still displays mobility even when bound. The bound conformer of DCT resembles that of DDM and provides very similar contacts with the receptor. Competition experiments indicate that both molecules compete with the taxane-binding site. A model of the binding mode of DDM and DCT to tubulin is proposed.

  13. Employing conformational analysis in the molecular modeling of agrochemicals: insights on QSAR parameters of 2,4-D

    Directory of Open Access Journals (Sweden)

    Matheus Puggina de Freitas

    2013-12-01

    Full Text Available A common practice to compute ligand conformations of compounds with various degrees of freedom to be used in molecular modeling (QSAR and docking studies is to perform a conformational distribution based on repeated random sampling, such as Monte-Carlo methods. Further calculations are often required. This short review describes some methods used for conformational analysis and the implications of using selected conformations in QSAR. A case study is developed for 2,4-dichlorophenoxyacetic acid (2,4-D, a widely used herbicide which binds to TIR1 ubiquitin ligase enzyme. The use of such an approach and semi-empirical calculations did not achieve all possible minima for 2,4-D. In addition, the conformations and respective energies obtained by the semi-empirical AM1 method do not match the calculated trends obtained by a high level DFT method. Similar findings were obtained for the carboxylate anion, which is the bioactive form. Finally, the crystal bioactive structure of 2,4-D was not found as a minimum when using Monte-Carlo/AM1 and is similarly populated with another conformer in implicit water solution according to optimization at the B3LYP/aug-cc-pVDZ level. Therefore, quantitative structure-activity relationship (QSAR methods based on three dimensional chemical structures are not fundamental to provide predictive models for 2,4-D congeners as TIR1 ubiquitin ligase ligands, since they do not necessarily reflect the bioactive conformation of this molecule. This probably extends to other systems.

  14. Molecular insight into conformational transmission of human P-glycoprotein

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Shan-Yan [Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Liu, Fu-Feng, E-mail: fufengliu@tju.edu.cn, E-mail: ysun@tju.edu.cn; Dong, Xiao-Yan; Sun, Yan, E-mail: fufengliu@tju.edu.cn, E-mail: ysun@tju.edu.cn [Department of Biochemical Engineering and Key Laboratory of Systems Bioengineering of the Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072 (China)

    2013-12-14

    P-glycoprotein (P-gp), a kind of ATP-binding cassette transporter, can export candidates through a channel at the two transmembrane domains (TMDs) across the cell membranes using the energy released from ATP hydrolysis at the two nucleotide-binding domains (NBDs). Considerable evidence has indicated that human P-gp undergoes large-scale conformational changes to export a wide variety of anti-cancer drugs out of the cancer cells. However, molecular mechanism of the conformational transmission of human P-gp from the NBDs to the TMDs is still unclear. Herein, targeted molecular dynamics simulations were performed to explore the atomic detail of the conformational transmission of human P-gp. It is confirmed that the conformational transition from the inward- to outward-facing is initiated by the movement of the NBDs. It is found that the two NBDs move both on the two directions (x and y). The movement on the x direction leads to the closure of the NBDs, while the movement on the y direction adjusts the conformations of the NBDs to form the correct ATP binding pockets. Six key segments (KSs) protruding from the TMDs to interact with the NBDs are identified. The relative movement of the KSs along the y axis driven by the NBDs can be transmitted through α-helices to the rest of the TMDs, rendering the TMDs to open towards periplasm in the outward-facing conformation. Twenty eight key residue pairs are identified to participate in the interaction network that contributes to the conformational transmission from the NBDs to the TMDs of human P-gp. In addition, 9 key residues in each NBD are also identified. The studies have thus provided clear insight into the conformational transmission from the NBDs to the TMDs in human P-gp.

  15. Molecular insight into conformational transmission of human P-glycoprotein

    Science.gov (United States)

    Chang, Shan-Yan; Liu, Fu-Feng; Dong, Xiao-Yan; Sun, Yan

    2013-12-01

    P-glycoprotein (P-gp), a kind of ATP-binding cassette transporter, can export candidates through a channel at the two transmembrane domains (TMDs) across the cell membranes using the energy released from ATP hydrolysis at the two nucleotide-binding domains (NBDs). Considerable evidence has indicated that human P-gp undergoes large-scale conformational changes to export a wide variety of anti-cancer drugs out of the cancer cells. However, molecular mechanism of the conformational transmission of human P-gp from the NBDs to the TMDs is still unclear. Herein, targeted molecular dynamics simulations were performed to explore the atomic detail of the conformational transmission of human P-gp. It is confirmed that the conformational transition from the inward- to outward-facing is initiated by the movement of the NBDs. It is found that the two NBDs move both on the two directions (x and y). The movement on the x direction leads to the closure of the NBDs, while the movement on the y direction adjusts the conformations of the NBDs to form the correct ATP binding pockets. Six key segments (KSs) protruding from the TMDs to interact with the NBDs are identified. The relative movement of the KSs along the y axis driven by the NBDs can be transmitted through α-helices to the rest of the TMDs, rendering the TMDs to open towards periplasm in the outward-facing conformation. Twenty eight key residue pairs are identified to participate in the interaction network that contributes to the conformational transmission from the NBDs to the TMDs of human P-gp. In addition, 9 key residues in each NBD are also identified. The studies have thus provided clear insight into the conformational transmission from the NBDs to the TMDs in human P-gp.

  16. Molecular motions and conformational transition between different conformational states of HIV-1 gp120 envelope glycoprotein

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The HIV-1 gp120 exterior envelope glycoprotein undergoes a series of conformational rearrangements while sequentially interacting with the receptor CD4 and coreceptor CCR5 or CXCR4 on the surface of host cells to initiate virus entry. Both the crystal structures of the HIV-1 gp120 core bound by the CD4 and antigen 17b and the SIV gp120 core prebound by CD4 are known. Despite the wealth of knowledge on these static snapshots of molecular conformations, the details of molecular motions involved in conformational transition that are crucial to intervention remain elusive. We presented comprehensive comparative analyses of the dynamics behaviors of the gp120 in its CD4-complexed, CD4-free and CD4-unliganded states based on the homology models with modeled V3 and V4 loops by means of CONCOORD computer simulation to generate ensembles of feasible protein structures that were subsequently analysed by essential dynamics analyses to identify preferred concerted motions. The revealed collective fluctuations are dominated by complex modes of combinational motions of the rotation/twisting, flexing/closure, and shortness/elongation between or within the inner, outer, and bridging-sheet domains, and these modes are related to the CD4 association and HIV neutralization avoidance. Further essential subspace overlap analyses were performed to quantitatively distinguish the preference for conformational transitions between the three states, revealing that the unliganded gp120 has a greater potential to translate its conformation into the conformational state adopted by the CD4-complexed gp120 than by the CD4-free gp120, whereas the CD4-free gp120 has a greater potential to translate its conformation into the unliganded state than the CD4-complexed gp120 does. These dy-namics data of gp120 in its different conformations are helpful in understanding the relationship be-tween the molecular motion/conformational transition and the function of gp120, and in gp120-structure-based subunit

  17. Molecularly stabilised ultrasmall gold nanoparticles: synthesis, characterization and bioactivity

    Science.gov (United States)

    Leifert, Annika; Pan-Bartnek, Yu; Simon, Ulrich; Jahnen-Dechent, Willi

    2013-06-01

    Gold nanoparticles (AuNPs) are widely used as contrast agents in electron microscopy as well as for diagnostic tests. Due to their unique optical and electrical properties and their small size, there is also a growing field of potential applications in medical fields of imaging and therapy, for example as drug carriers or as active compounds in thermotherapy. Besides their intrinsic optical properties, facile surface decoration with (bio)functional ligands renders AuNPs ideally suited for many industrial and medical applications. However, novel AuNPs may have toxicological profiles differing from bulk and therefore a thorough analysis of the quantitative structure-activity relationship (QSAR) is required. Several mechanisms are proposed that cause adverse effects of nanoparticles in biological systems. Catalytic generation of reactive species due to the large and chemically active surface area of nanomaterials is well established. Because nanoparticles approach the size of biological molecules and subcellular structures, they may overcome natural barriers by active or passive uptake. Ultrasmall AuNPs with sizes of 2 nm or less may even behave as molecular ligands. These types of potential interactions would imply a size and ligand-dependent behaviour of any nanomaterial towards biological systems. Thus, to fully understand their QSAR, AuNPs bioactivity should be analysed in biological systems of increasing complexity ranging from cell culture to whole animal studies.

  18. Two different molecular conformations found in chitosan type II salts.

    Science.gov (United States)

    Lertworasirikul, Amornrat; Tsue, Shin-ichiro; Noguchi, Keiichi; Okuyama, Kenji; Ogawa, Kozo

    2003-05-23

    The type II structure of chitosan acidic salts prepared from crab tendon in solid state was studied using an X-ray fiber diffraction technique together with the linked-atom least-squares (LALS) technique. The cylindrical Patterson method was applied to confirm the molecular conformation of the chitosan. It was shown that there are two different helical conformations for type II salts. One is the relaxed twofold helix having a tetrasaccharide as an asymmetric unit as found in chitosan.HCl salt, which was previously reported as a conformation of chitosan.HCOOH salt. The other is the fourfold helix having a disaccharide as an asymmetric unit newly found in chitosan.HI salt.

  19. Conformational homogeneity in molecular recognition by proteolytic enzymes.

    Science.gov (United States)

    Tyndall, J D; Fairlie, D P

    1999-01-01

    Crystal structures for several hundred protease-inhibitor complexes have been analysed and their superimpositions have been used to demonstrate a universal relationship between inhibitor/substrate conformation and molecular recognition by all aspartic, serine, cysteine and metallo proteases. Proteases universally recognize an extended beta strand conformation in all their peptidic (and non-peptidic) inhibitors and substrate analogues without significant exceptions. This conformational homogeneity is illustrated here for a subset of 180 protease-inhibitor structures which are displayed as (a) structural overlays of multiple inhibitors for each of eight aspartic, eight serine, six metallo and five cysteine proteases; (b) single inhibitors each bound to different proteases; and (c) Ramachandran plots of peptide or pseudo-peptide dihedral angle pairs which demonstrate beta strands (Phi -54 degrees to -173 degrees, Psi 24 degrees to 174 degrees ) like those normally found paired in proteins as beta sheets. However, unlike beta sheets, alpha and 3(10) helices, beta and gamma turns, where the folded main chain amide components are intramolecularly hydrogen bonded and thus unavailable for interaction with proteins, an inhibitor/substrate in an isolated beta strand conformation provides maximum exposure of its hydrogen bonding donors/acceptors and side chain components to a putative protease receptor. This analysis highlights the advantages of a strand conformation over other elements of secondary structure for protease recognition and may lead to generic strategies for inhibitor design.

  20. Mapping protein conformational energy landscapes using NMR and molecular simulation

    International Nuclear Information System (INIS)

    Nuclear magnetic resonance (NMR) spectroscopy provides detailed understanding of the nature and extent of protein dynamics on physiologically important timescales. We present recent advances in the combination of NMR with state-of-the art molecular simulation that are providing unique new insight into the motions on timescales from nanoseconds to milliseconds. In particular, we focus on methods based on residual dipolar couplings (RDCs) that allow for detailed mapping of the protein conformational energy landscape. A novel combination of RDCs with accelerated molecular dynamics allows for the development of ensemble representations of the underlying Boltzmann ensemble. (authors)

  1. Molecular mechanics study on conformation of perylene-quinonoid photosensitizers

    Institute of Scientific and Technical Information of China (English)

    张红雨; 张志义

    1997-01-01

    Using molecular mechanics method,values of the heat of formation (HF) of different conformations,of perylenequinonoid photosensitizes hypocrellin A (HA) and hypocrellin B (HB) were calculated and the variance of HF after phenolic protons’ dissociation were calculated as well The following was found:(i) The HF values of lour conformational isomers of HA and HB are similar to each other,so the four isomcrs can transform to each other room temperature,(ii) There exists the difference between the ability of dissociation of phenolic protons of HA and that of HB,the former is higher than the latter (iii) There exist two intramolecular hydrogen bonds in HA and HB The bond energy is approximately 8 kJ/mol and the energy of conformation Ⅰ is lower than that of conformationⅡ The bond energy of HA is lower than that of HB.(iv) There exists a low energy snot when phenolic hydroxyl bond twists 180° from the position where hydrogen bond is formed,which suggests that this kind of conformation probably exists,(v) Th

  2. Conformations of cyclopentasilane stereoisomers control molecular junction conductance

    DEFF Research Database (Denmark)

    Li, Haixing; Garner, Marc Hamilton; Shangguan, Zhichun;

    2016-01-01

    Here we examine the impact of ring conformation on the charge transport characteristics of cyclic pentasilane structures bound to gold electrodes in single molecule junctions. We investigate the conductance properties of alkylated cyclopentasilane cis and trans stereoisomers substituted in the 1......,3-position with methylthiomethyl electrode binding groups using both the scanning tunneling microscope-based break junction technique and density functional theory based ab initio calculations. In contrast with the linear ones, these cyclic silanes yield lower conductance values; calculations reveal...... that the constrained dihedral geometries occurring within the ring are suboptimal for σ-orbital delocalization, and therefore, conductance. Theoretical calculations reproduce the measured conductance trends for both cis and trans isomers and find several distinct conformations that are likely to form stable molecular...

  3. Optimization of a genetic algorithm for searching molecular conformer space

    Science.gov (United States)

    Brain, Zoe E.; Addicoat, Matthew A.

    2011-11-01

    We present two sets of tunings that are broadly applicable to conformer searches of isolated molecules using a genetic algorithm (GA). In order to find the most efficient tunings for the GA, a second GA - a meta-genetic algorithm - was used to tune the first genetic algorithm to reliably find the already known a priori correct answer with minimum computational resources. It is shown that these tunings are appropriate for a variety of molecules with different characteristics, and most importantly that the tunings are independent of the underlying model chemistry but that the tunings for rigid and relaxed surfaces differ slightly. It is shown that for the problem of molecular conformational search, the most efficient GA actually reduces to an evolutionary algorithm.

  4. Bioactive conformation of stromelysin inhibitors determined by transferred nuclear Overhauser effects.

    OpenAIRE

    Gonnella, N. C.; Bohacek, R; Zhang, X.; Kolossváry, I; Paris, C G; Melton, R; Winter, C; Hu, S I; Ganu, V

    1995-01-01

    The transferred nuclear Overhauser effect has been used to determine the biologically active conformations of two stromelysin inhibitors. Both inhibitors used in this study were hydroxamic acids generated via chemical synthesis. These structures, representing the conformation of each inhibitor bound to stromelysin, superimposed with excellent agreement. The study also provided information on the shape and orientation of the S2' and S1' pockets of the enzyme relative to thermolysin. Comparison...

  5. Design and synthesis of simplified taxol analogs based on the T-Taxol bioactive conformation

    OpenAIRE

    Zhao, Jielu; Bane, Susan; Snyder, James P.; Hu, Haipeng; Mukherjee, Kamalika; Slebodnick, Carla; Kingston, David G I

    2011-01-01

    A series of compounds designed to adopt a conformation similar to the tubulin-binding T-Taxol conformation of the anticancer drug paclitaxel has been synthesized. Both the internally bridged analogs 37-39, 41 and the open-chain analogs 27-29 and 43 were prepared. The bridged analogs 37-39 and 41 were synthesized by Grubbs' metatheses of compounds 30-32 and 33, which, in turn, were prepared by coupling β-lactams 24-26 with alcohols 22 and 23. Both the bridged and the open-chain analogs showed ...

  6. Influence of conformational molecular dynamics on matter wave interferometry

    CERN Document Server

    Gring, Michael; Eibenberger, Sandra; Nimmrichter, Stefan; Berrada, Tarik; Arndt, Markus; Ulbricht, Hendrik; Hornberger, Klaus; Müri, Marcel; Mayor, Marcel; Böckmann, Marcus; Doltsinis, Nikos

    2014-01-01

    We investigate the influence of thermally activated internal molecular dynamics on the phase shifts of matter waves inside a molecule interferometer. While de Broglie physics generally describes only the center-of-mass motion of a quantum object, our experiment demonstrates that the translational quantum phase is sensitive to dynamic conformational state changes inside the diffracted molecules. The structural flexibility of tailor-made hot organic particles is sufficient to admit a mixture of strongly fluctuating dipole moments. These modify the electric susceptibility and through this the quantum interference pattern in the presence of an external electric field. Detailed molecular dynamics simulations combined with density functional theory allow us to quantify the time-dependent structural reconfigurations and to predict the ensemble-averaged square of the dipole moment which is found to be in good agreement with the interferometric result. The experiment thus opens a new perspective on matter wave interfe...

  7. Enthalpy-Entropy Compensation upon Molecular Conformational Changes.

    Science.gov (United States)

    Ahmad, Mazen; Helms, Volkhard; Lengauer, Thomas; Kalinina, Olga V

    2015-04-14

    The change in free energy is the dominant factor in all chemical processes; it usually encompasses enthalpy-entropy compensation (EEC). Here, we use the free energy perturbation formalism to show that EEC is influenced by the molecular conformational changes (CCs) of the entire system comprising the solute and by the already known solvent reorganization. The internal changes of enthalpy and the entropy due to CCs upon modifying the interactions (perturbation) cancel each other exactly. The CCs influence the dissipation of the modified interactions and their contributions to the free energy. Using molecular simulations, we show that, for solvation of six different HIV-1 protease inhibitors, CCs in the solute cause EEC as large as 10-30 kcal/mol. Moreover, the EEC due to CCs in HIV-1 protease is shown to vary significantly upon modifying its bound ligand. These findings have important implications for understanding of EEC phenomena and for interpretation of thermodynamic measurements.

  8. Molecular dynamics simulations on structural conformations of rhodopsin and prion proteins

    International Nuclear Information System (INIS)

    Molecular dynamics simulations were performed to investigate the structural conformation of the rhodopsin and prion proteins. We have estimated the effect of specific disease-related amino acid mutations on the dynamics and conformational changes

  9. Syntheses and Bioactivities of Targeted and Conformationally Restrained Paclitaxel and Discodermolide Analogs

    OpenAIRE

    Yang, Chao

    2008-01-01

    Paclitaxel was isolated from the bark of Taxus brevifolia in the late 1960s. It exerts its biological effect by promoting tubulin polymerization and stabilizing the resulting microtubules. Paclitaxel has become one of the most important current drugs for the treatment of breast and ovarian cancers. Studies aimed at understanding the biologically active conformation of paclitaxel bound on ï ¢â tubulin are described. In this work, the synthesis of isotopically labeled taxol analogs is desc...

  10. Mechanical, Rheological, and Bioactivity Properties of Ultra High-Molecular-Weight Polyethylene Bioactive Composites Containing Polyethylene Glycol and Hydroxyapatite

    Directory of Open Access Journals (Sweden)

    Mazatusziha Ahmad

    2012-01-01

    Full Text Available Ultrahigh-molecular-weight polyethylene/high-density polyethylene (UHMWPE/HDPE blends prepared using polyethylene glycol PEG as the processing aid and hydroxyapatite (HA as the reinforcing filler were found to be highly processable using conventional melt blending technique. It was demonstrated that PEG reduced the melt viscosity of UHMWPE/HDPE blend significantly, thus improving the extrudability. The mechanical and bioactive properties were improved with incorporation of HA. Inclusion of HA from 10 to 50 phr resulted in a progressive increase in flexural strength and modulus of the composites. The strength increment is due to the improvement on surface contact between the irregular shape of HA and polymer matrix by formation of mechanical interlock. The HA particles were homogenously distributed even at higher percentage showed improvement in wetting ability between the polymer matrix and HA. The inclusion of HA enhanced the bioactivity properties of the composite by the formation of calcium phosphate (Ca-P precipitates on the composite surface as proven from SEM and XRD analysis.

  11. Sphingoid esters from the molecular distillation of squid oil: A preliminary bioactivity determination.

    Science.gov (United States)

    Saliu, Francesco; Longhin, Eleonora; Salanti, Anika; Degano, Ilaria; Della Pergola, Roberto

    2016-06-15

    A mixture of sphingoid esters was isolated (1.4% w/w) from the molecular distillation of crude squid visceral oil. A preliminary investigation on the bioactivity profile and toxic potential of this residue was carried out by in vitro experiments. No cytotoxicity and a moderate lipase inhibition activity were highlighted. PMID:26868543

  12. Molecular dynamics simulation study on zwitterionic structure to maintain the normal conformations of Glutathione

    Institute of Scientific and Technical Information of China (English)

    YAN; Han; ZHU; HaoMiao; SHEN; Jian

    2007-01-01

    Molecular dynamics simulations were applied to normal conformational Glutathione (GSH) and GSH over zwitterionic and hydrophobic surfaces respectively. Conformational analysis of GSH during the simulation time on RMSD, conformational flexibility and dihedral distribution were performed. The results showed that zwitterionic structure maintains the normal conformations of GSH to a better extent, which should be a first good proof of the hypothesis of "maintain of normal structure".

  13. Conformational analysis of methylphenidate: comparison of molecular orbital and molecular mechanics methods.

    Science.gov (United States)

    Gilbert, Kathleen M; Skawinski, William J; Misra, Milind; Paris, Kristina A; Naik, Neelam H; Buono, Ronald A; Deutsch, Howard M; Venanzi, Carol A

    2004-11-01

    Methylphenidate (MP) binds to the cocaine binding site on the dopamine transporter and inhibits reuptake of dopamine, but does not appear to have the same abuse potential as cocaine. This study, part of a comprehensive effort to identify a drug treatment for cocaine abuse, investigates the effect of choice of calculation technique and of solvent model on the conformational potential energy surface (PES) of MP and a rigid methylphenidate (RMP) analogue which exhibits the same dopamine transporter binding affinity as MP. Conformational analysis was carried out by the AM1 and AM1/SM5.4 semiempirical molecular orbital methods, a molecular mechanics method (Tripos force field with the dielectric set equal to that of vacuum or water) and the HF/6-31G* molecular orbital method in vacuum phase. Although all three methods differ somewhat in the local details of the PES, the general trends are the same for neutral and protonated MP. In vacuum phase, protonation has a distinctive effect in decreasing the regions of space available to the local conformational minima. Solvent has little effect on the PES of the neutral molecule and tends to stabilize the protonated species. The random search (RS) conformational analysis technique using the Tripos force field was found to be capable of locating the minima found by the molecular orbital methods using systematic grid search. This suggests that the RS/Tripos force field/vacuum phase protocol is a reasonable choice for locating the local minima of MP. However, the Tripos force field gave significantly larger phenyl ring rotational barriers than the molecular orbital methods for MP and RMP. For both the neutral and protonated cases, all three methods found the phenyl ring rotational barriers for the RMP conformers/invertamers (denoted as cte, tte, and cta) to be: cte, tte > MP > cta. Solvation has negligible effect on the phenyl ring rotational barrier of RMP. The B3LYP/6-31G* density functional method was used to calculate the

  14. Recognition of Conformational Changes in β-Lactoglobulin by Molecularly Imprinted Thin Films

    OpenAIRE

    Turner, Nicholas W.; Liu, Xiao; Piletsky, Sergey A.; Hlady, Vladimir; Britt, David W

    2007-01-01

    Pathogenesis in protein conformational diseases is initiated by changes in protein secondary structure. This molecular restructuring presents an opportunity for novel shape-based detection approaches, as protein molecular weight and chemistry are otherwise unaltered. Here we apply molecular imprinting to discriminate between distinct conformations of the model protein β-lactoglobulin (BLG). Thermal- and fluoro-alcohol-induced BLG isoforms were imprinted in thin films of 3-aminophenylboronic a...

  15. Conformational analysis of six- and twelve-membered ring compounds by molecular dynamics

    DEFF Research Database (Denmark)

    Christensen, I T; Jørgensen, Flemming Steen

    1997-01-01

    A molecular dynamics (MD)-based conformational analysis has been performed on a number of cycloalkanes in order to demonstrate the reliability and generality of MD as a tool for conformational analysis. MD simulations on cyclohexane and a series of methyl-substituted cyclohexanes were performed a...... provided 19 out of the 20 most stable conformations found in the MM2 force field. Finally, the general performance of the MD method for conformational analysis is discussed.......A molecular dynamics (MD)-based conformational analysis has been performed on a number of cycloalkanes in order to demonstrate the reliability and generality of MD as a tool for conformational analysis. MD simulations on cyclohexane and a series of methyl-substituted cyclohexanes were performed...

  16. Ligand induced conformational changes of the human serotonin transporter revealed by molecular dynamics simulations.

    Science.gov (United States)

    Koldsø, Heidi; Autzen, Henriette Elisabeth; Grouleff, Julie; Schiøtt, Birgit

    2013-01-01

    The competitive inhibitor cocaine and the non-competitive inhibitor ibogaine induce different conformational states of the human serotonin transporter. It has been shown from accessibility experiments that cocaine mainly induces an outward-facing conformation, while the non-competitive inhibitor ibogaine, and its active metabolite noribogaine, have been proposed to induce an inward-facing conformation of the human serotonin transporter similar to what has been observed for the endogenous substrate, serotonin. The ligand induced conformational changes within the human serotonin transporter caused by these three different types of ligands, substrate, non-competitive and competitive inhibitors, are studied from multiple atomistic molecular dynamics simulations initiated from a homology model of the human serotonin transporter. The results reveal that diverse conformations of the human serotonin transporter are captured from the molecular dynamics simulations depending on the type of the ligand bound. The inward-facing conformation of the human serotonin transporter is reached with noribogaine bound, and this state resembles a previously identified inward-facing conformation of the human serotonin transporter obtained from molecular dynamics simulation with bound substrate, but also a recently published inward-facing conformation of a bacterial homolog, the leucine transporter from Aquifex Aoelicus. The differences observed in ligand induced behavior are found to originate from different interaction patterns between the ligands and the protein. Such atomic-level understanding of how an inhibitor can dictate the conformational response of a transporter by ligand binding may be of great importance for future drug design. PMID:23776432

  17. Ligand induced conformational changes of the human serotonin transporter revealed by molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Heidi Koldsø

    Full Text Available The competitive inhibitor cocaine and the non-competitive inhibitor ibogaine induce different conformational states of the human serotonin transporter. It has been shown from accessibility experiments that cocaine mainly induces an outward-facing conformation, while the non-competitive inhibitor ibogaine, and its active metabolite noribogaine, have been proposed to induce an inward-facing conformation of the human serotonin transporter similar to what has been observed for the endogenous substrate, serotonin. The ligand induced conformational changes within the human serotonin transporter caused by these three different types of ligands, substrate, non-competitive and competitive inhibitors, are studied from multiple atomistic molecular dynamics simulations initiated from a homology model of the human serotonin transporter. The results reveal that diverse conformations of the human serotonin transporter are captured from the molecular dynamics simulations depending on the type of the ligand bound. The inward-facing conformation of the human serotonin transporter is reached with noribogaine bound, and this state resembles a previously identified inward-facing conformation of the human serotonin transporter obtained from molecular dynamics simulation with bound substrate, but also a recently published inward-facing conformation of a bacterial homolog, the leucine transporter from Aquifex Aoelicus. The differences observed in ligand induced behavior are found to originate from different interaction patterns between the ligands and the protein. Such atomic-level understanding of how an inhibitor can dictate the conformational response of a transporter by ligand binding may be of great importance for future drug design.

  18. Milk proteins-derived bioactive peptides in dairy products: molecular, biological and methodological aspects

    Directory of Open Access Journals (Sweden)

    Bartłomiej Dziuba

    2014-03-01

    Full Text Available Proteins are one of the primary components of the food, both in terms of nutrition and function. They are main source of amino acids, essential for synthesis of proteins, and also source of energy. Additionally, many proteins exhibit specifi c biological activities, which may have effect on functional or pro-health properties of food products. These proteins and their hydrolysis products, peptides, may infl uence the properties of food and human organism. The number of commercially available food products containing bioactive peptides is very low, apart from that milk proteins are their rich source. It could be supposed that number of available products with declared activity will rise in near future because of observed strong uptrend on interest in such products. Molecular and biological properties of milk proteins, as precursors of bioactive peptides was characterised in the work. Therefore, the strategy of research and obtaining of such peptides both in laboratory and industrial scale, as well as the range of their commercial application, was presented. Several examples of research efforts presenting high potential to develop new products containing bioactive peptides from milk proteins and predetermined as nutraceuticals was described.

  19. Milk proteins-derived bioactive peptides in dairy products: molecular, biological and methodological aspects.

    Science.gov (United States)

    Dziuba, Bartłomiej; Dziuba, Marta

    2014-01-01

    Proteins are one of the primary components of the food, both in terms of nutrition and function. They are main source of amino acids, essential for synthesis of proteins, and also source of energy. Additionally, many proteins exhibit specific biological activities, which may have effect on functional or pro-health properties of food products. These proteins and their hydrolysis products, peptides, may influence the properties of food and human organism. The number of commercially available food products containing bioactive peptides is very low, apart from that milk proteins are their rich source. It could be supposed that number of available products with declared activity will rise in near future because of observed strong uptrend on interest in such products. Molecular and biological properties of milk proteins, as precursors of bioactive peptides was characterised in the work. Therefore, the strategy of research and obtaining of such peptides both in laboratory and industrial scale, as well as the range of their commercial application, was presented. Several examples of research efforts presenting high potential to develop new products containing bioactive peptides from milk proteins and predetermined as nutraceuticals was described.

  20. Molecular, chemical and biological screening of soil actinomycete isolates in seeking bioactive peptide metabolites

    Directory of Open Access Journals (Sweden)

    Javad Hamedi

    2015-10-01

    Full Text Available Background and Objective: Due to the evolution of multidrug-resistant strains, screening of natural resources, especially actinomycetes, for new therapeutic agents discovery has become the interests of researchers. In this study, molecular, chemical and biological screening of soil actinomycetes was carried out in order to search for peptide-producing actinomycetes.Materials and Methods: 60 actinomycetes were isolated from soils of Iran. The isolates were subjected to molecular screening for detection NRPS (non-ribosomal peptide synthetases gene. Phylogenic identification of NRPS containing isolates was performed. Chemical screening of the crude extracts was performed using chlorine o-dianisidine as peptide detector reagent and bioactivity of peptide producing strains was determined by antimicrobial bioassay. High pressure liquid chromatography- mass spectrometry (HPLC-MS with UV-visible spectroscopy was performed for detection of the metabolite diversity in selected strain.Results: Amplified NRPS adenylation gene (700 bp was detected among 30 strains. Phylogenic identification of these isolates showed presence of rare actinomycetes genera among the isolates and 10 out of 30 strains were subjected to chemical screening. Nocardia sp. UTMC 751 showed antimicrobial activity against bacterial and fungal test pathogens. HPLC-MSand UV-visible spectroscopy results from the crude extract showed that this strain has probably the ability to produce new metabolites.Conclusion: By application of a combined approach, including molecular, chemical and bioactivity analysis, a promising strain of Nocardia sp. UTMC 751 was obtained. This strain had significant activity against Staphylococcus aureus and Pseudomonas aeruginosa. Strain Nocardia sp. UTMC 751 produce five unknown and most probably new metabolites with molecular weights of 274.2, 390.3, 415.3, 598.4 and 772.5. This strain had showed 99% similarity to Nocardia ignorata DSM 44496 T.

  1. Influence of Molecular Solvation on the Conformation of Star Polymers

    CERN Document Server

    Li, Xin; Sánchez-Diáz, Luis E; Do, Changwoo; Liu, Yun; Kim, Tae-Hwan; Smith, Gregory S; Hamilton, William A; Hong, Kunlun; Chen, Wei-Ren

    2014-01-01

    We have used neutron scattering to investigate the influence of concentration on the conformation of a star polymer. By varying the contrast between the solvent and isotopically labeled stars, we obtain the distributions of polymer and solvent within a star polymer from analysis of scattering data. A correlation between the local desolvation and the inward folding of star branches is discovered. From the perspective of thermodynamics, we find an analogy between the mechanism of polymer localization driven by solvent depletion and that of the hydrophobic collapse of polymers in solutions.

  2. Modeling and analysis of Schistosoma Argonaute protein molecular spatial conformation

    Institute of Scientific and Technical Information of China (English)

    Jianhua Zhang; Zhigang Shang; Xiaohui Zhang; Yuntao Zhang

    2011-01-01

    Objective: To analyze the amino acid sequence composition, secondary structure, the spatial conformation of its domain and other characteristics of Argonaute protein. Methods:Bioinformatics tools and the internet server were used. Firstly, the amino acid sequence composition features of the Argonaute protein were analyzed, and the phylogenetic tree was constructed. Secondly, Argonaute protein’s distribution of secondary structure and its physicochemical properties were predicted. Lastly, the protein functional expression form of the domain group was established through the Phyre-based analysis on the spatial conformation of Argonaute protein domains. Results: 593 amino acids were encoded by Argonaute protein, the phylogenetic tree was constructed, and Argonaute protein’s distribution of secondary structure and its physicochemical properties were obtained through analysis. In addition, the functional expression form which comprised the N-terminal PAZ domain and C-terminal Piwi domain for the Argonaute protein was obtained with Phyre. Conclusions: The information relationship between the structure and function of the Argonaute protein can be initially established with bioinformatics tools and the internet server, and this provides the theoretical basis for further clarifying the function of Schistosoma Argonaute protein.

  3. Extracting Conformational Ensembles of Small Molecules from Molecular Dynamics Simulations: Ampicillin as a Test Case

    Directory of Open Access Journals (Sweden)

    Giuliano Malloci

    2016-01-01

    Full Text Available The accurate and exhaustive description of the conformational ensemble sampled by small molecules in solution, possibly at different physiological conditions, is of primary interest in many fields of medicinal chemistry and computational biology. Recently, we have built an on-line database of compounds with antimicrobial properties, where we provide all-atom force-field parameters and a set of molecular properties, including representative structures extracted from cluster analysis over μs-long molecular dynamics (MD trajectories. In the present work, we used a medium-sized antibiotic from our sample, namely ampicillin, to assess the quality of the conformational ensemble. To this aim, we compared the conformational landscape extracted from previous unbiased MD simulations to those obtained by means of Replica Exchange MD (REMD and those originating from three freely-available conformer generation tools widely adopted in computer-aided drug-design. In addition, for different charge/protonation states of ampicillin, we made available force-field parameters and static/dynamic properties derived from both Density Functional Theory and MD calculations. For the specific system investigated here, we found that: (i the conformational statistics extracted from plain MD simulations is consistent with that obtained from REMD simulations; (ii overall, our MD-based approach performs slightly better than any of the conformer generator tools if one takes into account both the diversity of the generated conformational set and the ability to reproduce experimentally-determined structures.

  4. Molecular conformation and structural correlations of liquid D-1-propanol through neutron diffraction

    Indian Academy of Sciences (India)

    A Sahoo; S Sarkar; P S R Krishna; V Bhagat; R N Joarder

    2008-07-01

    An analysis of neutron diffraction data of liquid deuterated 1-propanol at room temperature to extract its molecular conformation is presented. Being a big molecule with twelve atomic sites, the analysis is tricky and needs careful consideration. The resulting molecular parameters are compared with electron diffraction (gas phase), X-ray diffraction (liquid phase) and MD simulation results. Information about the hydrogen-bonded intermolecular structure in liquid is extracted and nature of the probable molecular association suggested.

  5. Molecular dynamics simulations of conformation changes of HIV-1 regulatory protein on graphene

    Science.gov (United States)

    Zhao, Daohui; Li, Libo; He, Daohang; Zhou, Jian

    2016-07-01

    The fragment of viral protein R (Vpr), Vpr13-33, plays an important role in regulating nuclear importing of HIV genes through channel formation in which it adopts a leucine-zipper-like alpha-helical conformation. A recent experimental study reported that helical Vpr13-33 would transform to β-sheet or random coil structures and aggregate on the surface of graphene or graphene oxide through hydrophobic interactions. Due to experimental limitations, however, there is still a considerable lack of understanding on the adsorption dynamics at the early stage of the conformational transition at water-graphene interface and the underlying driving force at molecular level. In this study, atomistic molecular dynamics simulations were used to explore the conformation transition phenomena. Vpr13-33 kept α-helical structure in solution, but changed to β-sheet structure when strongly adsorbed onto graphene. Preferential adsorption of Vpr13-33 on graphene is dominated by hydrophobic interactions. The cluster analysis identified the most significant populated conformation and the early stage of structure conversion from α-helical to β-sheet was found, but the full β-sheet propagation was not observed. Free energy landscape analysis further complemented the transformation analysis of peptide conformations. These findings are consistent with experimental results, and give a molecular level interpretation for the reduced cytotoxicity of Vpr13-33 to some extent upon graphene exposure. Meanwhile, this study provides some significant insights into the detailed mechanism of graphene-induced protein conformation transition.

  6. Isolation and molecular characterization of bioactive secondary metabolites fromCallyspongia spp. associated fungi

    Institute of Scientific and Technical Information of China (English)

    Meenupriya J; Thangaraj M

    2010-01-01

    Objective:To isolate and characterize the bioactive secondary metabolite fromCallyspongia spp. associated fungi.Methods:In vitro antibacterial screening of fungi associated with Callyspongia species, collected from south east coast of India, against selected clinical isolates of bacteria were conducted in this study. The extracts showing good antimicrobial activity were subjected to further analysis to identify the active constituents sponge associated fungi (both biomass and filtrate) with five different solvents. The compound responsible for bioactivity was characterized using Fouvier-transform infrared (FT-IR) and gas chromatography-mass spectrometry(GC-MS) instrumental analysis to identify the functional group and compound. The molecular characterization of the elite fungal strains were done by isolating their genomicDNA and amplify the internal transcribed spacer(ITS) region of5.8srRNA using specific ITS primer. The novelty of the strain was proved by BlastN analysis against non-redundant(NR) database and hence was submitted to GenBank.Results: Active compound was Desmethylnomifensine confirmed byGC-MS and the potent fungi wasAspergillus flavusGU815344.Conclusions:The isolate exhibits a marked antagonistic activity against potential bacterial pathogens thus illuminating the advanced researches in this decade to focus on clinical pharmacology to identify novel therapeutic targets. The present study depicts a promising scenario to focus onAspergillus flavus derived compounds which can be easily scaled up for large biomass production and stable formulation as a drug.

  7. Conformational and functional analysis of molecular dynamics trajectories by Self-Organising Maps

    Directory of Open Access Journals (Sweden)

    Stella Fabio

    2011-05-01

    Full Text Available Abstract Background Molecular dynamics (MD simulations are powerful tools to investigate the conformational dynamics of proteins that is often a critical element of their function. Identification of functionally relevant conformations is generally done clustering the large ensemble of structures that are generated. Recently, Self-Organising Maps (SOMs were reported performing more accurately and providing more consistent results than traditional clustering algorithms in various data mining problems. We present a novel strategy to analyse and compare conformational ensembles of protein domains using a two-level approach that combines SOMs and hierarchical clustering. Results The conformational dynamics of the α-spectrin SH3 protein domain and six single mutants were analysed by MD simulations. The Cα's Cartesian coordinates of conformations sampled in the essential space were used as input data vectors for SOM training, then complete linkage clustering was performed on the SOM prototype vectors. A specific protocol to optimize a SOM for structural ensembles was proposed: the optimal SOM was selected by means of a Taguchi experimental design plan applied to different data sets, and the optimal sampling rate of the MD trajectory was selected. The proposed two-level approach was applied to single trajectories of the SH3 domain independently as well as to groups of them at the same time. The results demonstrated the potential of this approach in the analysis of large ensembles of molecular structures: the possibility of producing a topological mapping of the conformational space in a simple 2D visualisation, as well as of effectively highlighting differences in the conformational dynamics directly related to biological functions. Conclusions The use of a two-level approach combining SOMs and hierarchical clustering for conformational analysis of structural ensembles of proteins was proposed. It can easily be extended to other study cases and to

  8. Molecular Regulation of Adipogenesis and Potential Anti-Adipogenic Bioactive Molecules

    Directory of Open Access Journals (Sweden)

    Dorothy Moseti

    2016-01-01

    Full Text Available Adipogenesis is the process by which precursor stem cells differentiate into lipid laden adipocytes. Adipogenesis is regulated by a complex and highly orchestrated gene expression program. In mammalian cells, the peroxisome proliferator-activated receptor γ (PPARγ, and the CCAAT/enhancer binding proteins (C/EBPs such as C/EBPα, β and δ are considered the key early regulators of adipogenesis, while fatty acid binding protein 4 (FABP4, adiponectin, and fatty acid synthase (FAS are responsible for the formation of mature adipocytes. Excess accumulation of lipids in the adipose tissue leads to obesity, which is associated with cardiovascular diseases, type II diabetes and other pathologies. Thus, investigating adipose tissue development and the underlying molecular mechanisms is vital to develop therapeutic agents capable of curbing the increasing incidence of obesity and related pathologies. In this review, we address the process of adipogenic differentiation, key transcription factors and proteins involved, adipogenic regulators and potential anti-adipogenic bioactive molecules.

  9. Molecular conformation and liquid structure of 2-propanol through neutron diffraction

    Indian Academy of Sciences (India)

    A Sahoo; S Sarkar; P S R Krishna; R N Joarder

    2010-05-01

    The neutron diffraction data analysis of deuterated liquid 2-propanol at room temperature to define its molecular conformation is presented. 2-Propanol being a large molecule with twelve atomic sites, the conformation analysis is tricky and an improved method of data analysis is given. The intermolecular structural correlations, i.e., hydrogen-bonded liquid structure, can be modelled accurately to extract the nature of the average hydrogen-bonded molecular association in liquid state at room temperature. Like other alcohols these are mostly hexamer ring chain (HRC) clusters. The cluster analysis of recent X-ray data available in the literature also support the same liquid structure.

  10. Influence of sodium alginate pretreated by ultrasound on papain properties: Activity, structure, conformation and molecular weight and distribution.

    Science.gov (United States)

    Feng, Liping; Cao, Yanping; Xu, Duoxia; You, Sasa; Han, Fu

    2016-09-01

    The aim of the study was to investigate the impact of sodium alginate (ALG) pretreated by ultrasound on the enzyme activity, structure, conformation and molecular weight and distribution of papain. ALG solutions were pretreated with ultrasound at varying power (0.05, 0.15, 0.25, 0.35, 0.45W/cm(2)), 135kHz, 50°C for 20min. The maximum relative activity of papain increased by 10.53% when mixed with ALG pretreated by ultrasound at 0.25W/cm(2), compared with the untreated ALG. The influence of ultrasound pretreated ALG on the conformation and secondary structure of papain were assessed by fluorescence spectroscopy and circular dichroism spectroscopy. The fluorescence spectra revealed that ultrasound pretreated ALG increased the number of tryptophan on papain surface, especially at 0.25W/cm(2). It indicated that ultrasound pretreatment induced molecular unfolding, causing the exposure of more hydrophobic groups and regions from inside to the outside of the papain molecules. Furthermore, ultrasound pretreated ALG resulted in minor changes in the secondary structure of the papain. The content of α-helix was slightly increased after ultrasound pretreatment and no significant change was observed at different ultrasound powers. ALG pretreated by ultrasound enhanced the stability of the secondary structure of papain, especially at 0.25W/cm(2). The free sulfhydryl (SH) content of papain was slightly increased and then decreased with the increase of ultrasonic power. The maximum content of free SH was observed at 0.25W/cm(2), under which the content of the free SH increased by 6.36% compared with the untreated ALG. Dynamic light scattering showed that the effect of ultrasound treatment was mainly the homogenization of the ALG particles in the mixed dispersion. The gel permeation chromatography coupled with the multi-angle laser light scattering photometer analysis showed that the molecular weight (Mw) of papain/ALG was decreased and then increased with the ultrasonic

  11. Molecular dynamics simulations of poly (ethylene oxide) hydration and conformation in solutions

    Science.gov (United States)

    Dahal, Udaya; Dormidontova, Elena

    Polyethylene oxide (PEO) is one of the most actively used polymers, especially in biomedical applications due to its high hydrophilicity, biocompatibility and potency to inhibit protein adsorption. PEO solubility and conformation in water depends on its capability to form hydrogen bonds. Using atomistic molecular dynamics simulations we investigated the details of water packing around PEO chain and characterized the type and lifetime of hydrogen bonds in aqueous and mixed solvent solutions. The observed polymer chain conformation varies from an extended coil in pure water to collapsed globule in hexane and a helical-like conformation in pure isobutyric acid or isobutyric acid -water mixture in agreement with experimental observations. We'll discuss the implications of protic solvent arrangement and stability of hydrogen bonds on PEO chain conformation and mobility. This research is supported by NSF (DMR-1410928).

  12. Conformational analysis of 2,2'-arylmethylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one) by NMR and molecular modeling

    Energy Technology Data Exchange (ETDEWEB)

    Ferreira, Marcelle de S.; Figueroa-Villar, Jose D., E-mail: jdfv2009@gmail.com [Instituto Militar de Engenharia (IME), Rio de Janeiro, RJ (Brazil). Dept. de Quimica. Grupo de Medicina Quimica

    2014-05-15

    2,2'-arylmethylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-ones) with para and ortho-R groups on the benzene ring were prepared and studied by nuclear magnetic resonance (NMR) and molecular modeling to determine their conformational exchanges. Experimental and calculated results indicated conformational interconversions in these compounds by rotation of benzene ring and slow movement of dimedone rings, leading to intramolecular hydrogen bond length variation. The presence of one R group at the ortho position on the benzene ring modifies conformational exchange, leading to disappearance of one intramolecular hydrogen bond and superposition of diverse NMR signals. The correlation of σ{sub p} values with chemical shifts, angles and atomic charges confirms that para-R groups electronic properties are involved in conformational exchange and chemical shift variance. These results will be used to study the interaction of these compounds with bio-molecules and their use as starting materials for design and synthesis of new bioactive agents. (author)

  13. Conformational analysis of 2,2'-arylmethylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one) by NMR and molecular modeling

    International Nuclear Information System (INIS)

    2,2'-arylmethylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-ones) with para and ortho-R groups on the benzene ring were prepared and studied by nuclear magnetic resonance (NMR) and molecular modeling to determine their conformational exchanges. Experimental and calculated results indicated conformational interconversions in these compounds by rotation of benzene ring and slow movement of dimedone rings, leading to intramolecular hydrogen bond length variation. The presence of one R group at the ortho position on the benzene ring modifies conformational exchange, leading to disappearance of one intramolecular hydrogen bond and superposition of diverse NMR signals. The correlation of σp values with chemical shifts, angles and atomic charges confirms that para-R groups electronic properties are involved in conformational exchange and chemical shift variance. These results will be used to study the interaction of these compounds with bio-molecules and their use as starting materials for design and synthesis of new bioactive agents. (author)

  14. Methodologies for conformational studies of oligo- and poly-glucans: crystallography and molecular mechanics

    International Nuclear Information System (INIS)

    After some considerations on the conformational analysis of polysaccharides, this research thesis outlines the interest of molecular mechanics as a method to study these components. Technical aspects are presented. The author reports the prediction of the conformations of some specific cyclic oligomers (glucans, glucore), the use of X-ray diffraction to study glucides (and the limitations of this method). He reports the search for another investigation method: relationships between X rays and molecular mechanics, situation with respect to other crystallographic methods, presentation of principle of the 'Packing' method, and applications. He reports the study of regular conformations of polysaccharides, the study of the statistic configuration of polymer chains and the application to alpha-glucans

  15. Molecular mechanics work station for protein conformational studies

    Energy Technology Data Exchange (ETDEWEB)

    Fine, R.; Levinthal, C.; Schoenborn, B.; Dimmier, G.; Rankowitz, C.

    1984-01-01

    Interest in computational problems in Biology has intensified over the last few years, partly due to the development of techniques for the rapid cloning, sequencing, and mutagenesis of genes from organisims ranging from E. coli to Man. The central dogma of molecular biology; that DNA codes for mRNA which codes for protein, has been understood in a linear programming sense since the genetic code was cracked. But what is not understood at present is how a protein, once assembled as a long sequence of amino acids, folds back on itself to produce a three-dimensional structure which is unique to that protein and which dictates its chemical and biological activity. This folding process is purely physics, and involves the time evolution of a system of several thousand atoms which interact with each other and with atoms from the surrounding solvent. Molecular dynamics simulations on smaller molecules suggest that approaches which treat the protein as a classical ensemble of atoms interacting with each other via an empirical Hamiltonian can yield the kind of predictive results one would like when applied to proteins.

  16. Current-Driven Conformational Changes, Charging and Negative Differential Resistance in Molecular Wires

    OpenAIRE

    Emberly, Eldon; Kirczenow, George

    2001-01-01

    We introduce a theoretical approach based on scattering theory and total energy methods that treats transport non-linearities, conformational changes and charging effects in molecular wires in a unified way. We apply this approach to molecular wires consisting of chain molecules with different electronic and structural properties bonded to metal contacts. We show that non-linear transport in all of these systems can be understood in terms of a single physical mechanism and predict that negati...

  17. Molecular dynamics simulations of biological membranes and membrane proteins using enhanced conformational sampling algorithms.

    Science.gov (United States)

    Mori, Takaharu; Miyashita, Naoyuki; Im, Wonpil; Feig, Michael; Sugita, Yuji

    2016-07-01

    This paper reviews various enhanced conformational sampling methods and explicit/implicit solvent/membrane models, as well as their recent applications to the exploration of the structure and dynamics of membranes and membrane proteins. Molecular dynamics simulations have become an essential tool to investigate biological problems, and their success relies on proper molecular models together with efficient conformational sampling methods. The implicit representation of solvent/membrane environments is reasonable approximation to the explicit all-atom models, considering the balance between computational cost and simulation accuracy. Implicit models can be easily combined with replica-exchange molecular dynamics methods to explore a wider conformational space of a protein. Other molecular models and enhanced conformational sampling methods are also briefly discussed. As application examples, we introduce recent simulation studies of glycophorin A, phospholamban, amyloid precursor protein, and mixed lipid bilayers and discuss the accuracy and efficiency of each simulation model and method. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov.

  18. Conformation, molecular packing and field effect mobility of regioregular beta,beta'-dihexylsexithiophiophene

    DEFF Research Database (Denmark)

    Kiriy, N.; Kiriy, A.; Bocharova, V.;

    2004-01-01

    ) V-1 s(-1), which is considerably less than the FEM of alpha,omega-DH6T. To understand the reason for such poor macroscopic electrical properties, the conformation and the molecular packing of beta,beta'-DH6T were systematically studied by means of UV-vis spectroscopy, scanning electron microscopy...

  19. New approaches for molecular conformer force field analysis in combination with ab initio results

    Science.gov (United States)

    Kuramshina, G. M.; Pentin, Yu. A.; Yagola, A. G.

    1999-10-01

    Ab initio and DFT results on harmonic force constants for trans- and gauche-conformers of CH 3CH 2CH 2Cl, CF 3CH 2CH 2Cl and CCl 3CH 2CH 2Cl are used for formulating constraints in molecular force field models described compounds with hindered internal rotation around the C-C bond.

  20. Parallel Cascade Selection Molecular Dynamics (PaCS-MD) to generate conformational transition pathway.

    Science.gov (United States)

    Harada, Ryuhei; Kitao, Akio

    2013-07-21

    Parallel Cascade Selection Molecular Dynamics (PaCS-MD) is proposed as a molecular simulation method to generate conformational transition pathway under the condition that a set of "reactant" and "product" structures is known a priori. In PaCS-MD, the cycle of short multiple independent molecular dynamics simulations and selection of the structures close to the product structure for the next cycle are repeated until the simulated structures move sufficiently close to the product. Folding of 10-residue mini-protein chignolin from the extended to native structures and open-close conformational transition of T4 lysozyme were investigated by PaCS-MD. In both cases, tens of cycles of 100-ps MD were sufficient to reach the product structures, indicating the efficient generation of conformational transition pathway in PaCS-MD with a series of conventional MD without additional external biases. Using the snapshots along the pathway as the initial coordinates, free energy landscapes were calculated by the combination with multiple independent umbrella samplings to statistically elucidate the conformational transition pathways.

  1. DFT molecular modeling and NMR conformational analysis of a new longipinenetriolone diester

    Science.gov (United States)

    Cerda-García-Rojas, Carlos M.; Guerra-Ramírez, Diana; Román-Marín, Luisa U.; Hernández-Hernández, Juan D.; Joseph-Nathan, Pedro

    2006-05-01

    The structure and conformational behavior of the new natural compound (4 R,5 S,7 S,8 R,9 S,10 R,11 R)-longipin-2-en-7,8,9-triol-1-one 7-angelate-9-isovalerate (1) isolated from Stevia eupatoria, were studied by molecular modeling and NMR spectroscopy. A Monte Carlo search followed by DFT calculations at the B3LYP/6-31G* level provided the theoretical conformations of the sesquiterpene framework, which were in full agreement with results derived from the 1H- 1H coupling constant analysis.

  2. Theoretical studies on the molecular structure, conformational preferences, topological and vibrational analysis of allicin

    Science.gov (United States)

    Durlak, Piotr; Berski, Sławomir; Latajka, Zdzisław

    2016-01-01

    The molecular structure, conformational preferences, topological and vibrational analysis of allicin has been investigated at two different approaches. Calculations have been carried out on static (DFT and MP2) levels with an assortment of Dunning's basis sets and dynamic CPMD simulations. In this both case within the isolated molecule approximation. The results point out that at least twenty different conformers coexist on the PES as confirmed by the flexible character of this molecule. The topological analysis of ELF showed very similar nature of the Ssbnd S and Ssbnd O bonds. The infrared spectrum has been calculated, and a comparative vibrational analysis has been performed.

  3. S-Shaped Conformation of the Quaterthiophene Molecular Backbone in Two-Dimensional Bisterpyridine-Derivative Self-Assembled Nanoarchitecture.

    Science.gov (United States)

    Kervella, Yann; Shilova, Ekaterina; Latil, Sylvain; Jousselme, Bruno; Silly, Fabien

    2015-12-15

    The conformation and the two-dimensional self-assembly of 4'-(3',4″-dihexyloxy-5,2':5',2″:5″,2‴-quaterthien-2,5‴-diyl)-bis(2,2':6',2″-terpyridine) molecules are theoretically and experimentally investigated. This molecular building block forms a hydrogen-bonded chiral supramolecular nanoarchitecture on graphite at the solid/liquid interface. Scanning tunneling microscopy (STM) shows that the molecule adopts an S-shaped conformation in this structure. DFTB+ calculations reveal that this conformation is not the lowest-energy conformation. The molecular nanoarchitecture appears to be stabilized by hydrogen bonding as well as van der Waals interactions. I-, L-, and D-shaped molecular conformations are, however, locally observed at the domain boundary, but these conformations do not self-assemble into organized 2D structures. PMID:26624809

  4. Molecular modeling of the conformational dynamics of the cellular prion protein

    Science.gov (United States)

    Nguyen, Charles; Colling, Ian; Bartz, Jason; Soto, Patricia

    2014-03-01

    Prions are infectious agents responsible for transmissible spongiform encephalopathies (TSEs), a type of fatal neurodegenerative disease in mammals. Prions propagate biological information by conversion of the non-pathological version of the prion protein to the infectious conformation, PrPSc. A wealth of knowledge has shed light on the nature and mechanism of prion protein conversion. In spite of the significance of this problem, we are far from fully understanding the conformational dynamics of the cellular isoform. To remedy this situation we employ multiple biomolecular modeling techniques such as docking and molecular dynamics simulations to map the free energy landscape and determine what specific regions of the prion protein are most conductive to binding. The overall goal is to characterize the conformational dynamics of the cell form of the prion protein, PrPc, to gain insight into inhibition pathways against misfolding. NE EPSCoR FIRST Award to Patricia Soto.

  5. Study of Two Bioactive Peptides in Vacuum and Solvent by Molecular Modeling

    Science.gov (United States)

    Yaşar, F.; Demir, K.

    The thermodynamic and structural properties of Tyrosine-Glycine-Leusine-Phenylalanine (YGLF, in a one letter code) and Lysine-Valine-Leusine-Proline-Valine-Proline-Glutamine (KVLPVPQ) peptide sequences were studied by three-dimensional molecular modeling in vacuum and solution. All the three-dimensional conformations of each peptide sequences were obtained by multicanonical simulations with using ECEPP/2 force field and each simulation started from completely random initial conformation. Solvation contributions are included by a term that is proportional to solvent-accessible surface areas of peptides. In the present study, we calculated the average values of total energy, specific heat, fourth-order cumulant and end-to-end distance for two peptide sequences of milk protein as a function of temperature. With using major advantage of this simulation technique, Ramachandran plots were prepared and analysed to predict the relative occurrence probabilities of β-turn, γ-turn and helical structures. Although structural predictions of these sequences indicate both the presence of high level of γ-turns and low level of β-turns in vacuum and solvent, it was observed that these probabilities in vacuum were higher than the ones in solvent model.

  6. Impact of molecular weight on the formation of electrosprayed chitosan microcapsules as delivery vehicles for bioactive compounds.

    Science.gov (United States)

    Gómez-Mascaraque, Laura G; Sanchez, Gloria; López-Rubio, Amparo

    2016-10-01

    The molecular weight of chitosan is one of its most determinant characteristics, which affects its processability and its performance as a biomaterial. However, information about the effect of this parameter on the formation of electrosprayed chitosan microcapsules is scarce. In this work, the impact of chitosan molecular weight on its electrosprayability was studied and correlated with its effect on the viscosity, surface tension and electrical conductivity of solutions. A Discriminant Function Analysis revealed that the morphology of the electrosprayed chitosan materials could be correctly predicted using these three parameters for almost 85% of the samples. The suitability of using electrosprayed chitosan capsules as carriers for bioactive agents was also assessed by loading them with a model active compound, (-)-epigallocatechin gallate (EGCG). This encapsulation, with an estimated efficiency of around 80% in terms of preserved antioxidant activity, showed the potential to prolong the antiviral activity of EGCG against murine norovirus via gradual bioactive release combined with its protection against degradation in simulated physiological conditions.

  7. A molecular simulation study of the protection of insulin bioactive structure by trehalose.

    Science.gov (United States)

    Li, Daixi; Liu, Li; Yu, Huaxing; Zhai, Zhen; Zhang, Yan; Guo, Baisong; Yang, Chunsheng; Liu, Baolin

    2014-11-01

    Biopharmaceuticals are proteins with a crucial role in the treatment of many diseases. However, these protein medicines are often thermally labile and therefore unsuitable for long-term application and storage, as they tend to lose their activity under ambient conditions. Desiccation is one approach to improving protein stability, but the drying process itself can cause irreversible damage. In the current study, insulin was chosen as an example of a thermally sensitive biopharmaceutical to investigate whether the disaccharide, trehalose, can prevent loss of structural integrity due to drying. The experiment was performed using replica exchange molecular simulation and Gromacs software with a Gromos96 (53a6) force field. The results indicate that trehalose preserves the bioactive structure of insulin during drying, consistent with the use of trehalose as a protectant for thermally sensitive biopharmaceuticals. For instance, at the water content of 1.77%, insulin without any protectants yields the highest RMSD value as 0.451 nm, then the RMSD of insulin in presence of trehalose only ca. 0.100 nm.

  8. Molecular mechanics approach for design and conformational studies of macrocyclic ligands

    International Nuclear Information System (INIS)

    Computational Chemistry has revolutionized way of viewing molecules at the quantum mechanical scale by allowing simulating various chemical scenarios that are not possible to study in a laboratory. The remarkable applications of computational chemistry have promoted to design and test of the effectiveness of various methods for searching the conformational space of highly flexible molecules. In this context, we conducted a series of optimization and conformational searches on macrocyclic based ligands, 9N3Me5Ox, (1,4,7-tris(5-methyl-8-hydroxyquinoline)-1,4,7-triazacyclononane) and 12N3Me5Ox, (1,5,9-tris(5-methyl-8-hydroxyquinoline)-1,5,9-triazacyclododecane) and studied their selectivity and coordination behavior with some lanthanide metal ions in molecular mechanics and semiempirical methods. The methods include both systematic and random conformational searches for dihedral angles, torsion angles and Cartesian coordinates. Structural studies were carried out by using geometry optimization, coordination scans and electronic properties were evaluated. The results clearly show that chair-boat conformational isomer of 9N3Me5Ox ligand is more stable due to lower eclipsing ethane interaction and form stronger adduct complexes with lanthanide metal ion. This is because of the fact that, in a central unit of 9N3 of the ligand form six endo type bonds out of nine. The rest of bonds have trans conformation. In contrast, for the adduct of 12N3Me5Ox, two C-C bonds have on eclipsed conformation, and others have synclinal and antiperiplanar confirmations. The distortion of the two eclipsed conformations may affect the yields and the stability of the complexes

  9. Molecular mechanics approach for design and conformational studies of macrocyclic ligands

    Energy Technology Data Exchange (ETDEWEB)

    Rohini,; Akbar, Rifat; Kanungo, B. K., E-mail: b.kanungo@gmail.com [Department of Chemistry, Sant Longowal Institute of Engineering & Technology, Longowal-148106 (India)

    2015-08-28

    Computational Chemistry has revolutionized way of viewing molecules at the quantum mechanical scale by allowing simulating various chemical scenarios that are not possible to study in a laboratory. The remarkable applications of computational chemistry have promoted to design and test of the effectiveness of various methods for searching the conformational space of highly flexible molecules. In this context, we conducted a series of optimization and conformational searches on macrocyclic based ligands, 9N3Me5Ox, (1,4,7-tris(5-methyl-8-hydroxyquinoline)-1,4,7-triazacyclononane) and 12N3Me5Ox, (1,5,9-tris(5-methyl-8-hydroxyquinoline)-1,5,9-triazacyclododecane) and studied their selectivity and coordination behavior with some lanthanide metal ions in molecular mechanics and semiempirical methods. The methods include both systematic and random conformational searches for dihedral angles, torsion angles and Cartesian coordinates. Structural studies were carried out by using geometry optimization, coordination scans and electronic properties were evaluated. The results clearly show that chair-boat conformational isomer of 9N3Me5Ox ligand is more stable due to lower eclipsing ethane interaction and form stronger adduct complexes with lanthanide metal ion. This is because of the fact that, in a central unit of 9N3 of the ligand form six endo type bonds out of nine. The rest of bonds have trans conformation. In contrast, for the adduct of 12N3Me5Ox, two C-C bonds have on eclipsed conformation, and others have synclinal and antiperiplanar confirmations. The distortion of the two eclipsed conformations may affect the yields and the stability of the complexes.

  10. Physico-chemical characterization of chitosan-based edible films incorporating bioactive compounds of different molecular weight

    OpenAIRE

    Bourbon, A. I.; A.C. Pinheiro; Cerqueira, M. A.; Rocha, Cristina M. R.; Avides, Maria do Carmo; Quintas, Mafalda A. C.; Vicente, A.A.

    2011-01-01

    Chitosan packaging films containing different bioactive compounds (a peptide fraction from whey protein concentrate (WPC) hydrolysate, glycomacropeptide (GMP) and lactoferrin) were produced and their mechanical and barrier properties were evaluated. The molecular weight of protein-based compounds was determined using SDS–PAGE. The addition of GMP and lactoferrin to chitosan film caused a significant reduction of tensile strength and the elongation-at-break significantly increased ...

  11. Molecular Dynamics Simulations of Insulin: Elucidating the Conformational Changes that Enable Its Binding.

    Directory of Open Access Journals (Sweden)

    Anastasios Papaioannou

    Full Text Available A sequence of complex conformational changes is required for insulin to bind to the insulin receptor. Recent experimental evidence points to the B chain C-terminal (BC-CT as the location of these changes in insulin. Here, we present molecular dynamics simulations of insulin that reveal new insights into the structural changes occurring in the BC-CT. We find three key results: 1 The opening of the BC-CT is inherently stochastic and progresses through an open and then a "wide-open" conformation--the wide-open conformation is essential for receptor binding, but occurs only rarely. 2 The BC-CT opens with a zipper-like mechanism, with a hinge at the Phe24 residue, and is maintained in the dominant closed/inactive state by hydrophobic interactions of the neighboring Tyr26, the critical residue where opening of the BC-CT (activation of insulin is initiated. 3 The mutation Y26N is a potential candidate as a therapeutic insulin analogue. Overall, our results suggest that the binding of insulin to its receptor is a highly dynamic and stochastic process, where initial docking occurs in an open conformation and full binding is facilitated through interactions of insulin receptor residues with insulin in its wide-open conformation.

  12. Molecular structure and conformational preferences of gaseous 1-iodo-1-silacyclohexane

    Science.gov (United States)

    Belyakov, A. V.; Baskakov, A. A.; Berger, R. J. F.; Mitzel, N. W.; Oberhammer, H.; Arnason, I.; Wallevik, S. Ò.

    2012-03-01

    The molecular structure of the axial and equatorial conformers of 1-iodo-1-silacyclohexane, CH2(CH2CH2)2SiH-I, as well as thermodynamic equilibrium between these species were investigated by means of gas-phase electron diffraction (GED) and quantum chemical calculations up to MP2(full)/SDB-AUG-CC-pVTZ level of theory (MP2). According to electron diffraction data, the vapor of this compound comprises a mixture of conformers with chair conformation and Cs symmetry differing in the axial and equatorial position of the Si-I bond (axial = 73(7) mol%/equatorial = 27(7) mol%) at T = 352 K. This corresponds to a free energy difference of A = -0.59(22) kcal mol-1. The observed gas-phase electron diffraction parameters are in good agreement with those obtained from theory. NBO analysis revealed that axial conformer of 1-iodo-1-silacyclohexane is an example for electrostatic stabilization of a conformer which is unfavorable in terms of steric and conjugation interaction.

  13. Studies of (-)-pironetin binding to α-tubulin: conformation, docking, and molecular dynamics.

    Science.gov (United States)

    Bañuelos-Hernández, Angel E; Mendoza-Espinoza, José Alberto; Pereda-Miranda, Rogelio; Cerda-García-Rojas, Carlos M

    2014-05-01

    A comprehensive conformational analysis for the anticancer agent pironetin (1) was achieved by molecular modeling using density functional theory calculations at the B3PW91/DGTZVP level in combination with calculated and experimental (1)H-(1)H coupling constants comparison. Two solvent-dependent conformational families (L and M) were revealed for the optimum conformations. Docking studies of the pironetin-tubulin complex determined a quantitative model for the hydrogen-bond interactions of pironetin through the αAsn249, αAsn258, and αLys352 amino groups in α-tubulin, which supported the formation of a covalent adduct between the αLys352 and the β carbon atom of the α,β-unsaturated lactone. Saturation-transfer difference NMR spectroscopy confirmed that pironetin binds to tubulin, while molecular dynamics exposed a distortion of the tubulin secondary structure at the H8 and H10 α-helices as well as at the S9 β-sheet, where αLys352 is located. A large structural perturbation in the M-loop geometry between the αIle274 and αLeu285 residues, an essential region for molecular recognition between α-α and β-β units of protofilaments, was also identified and provided a rationale for the pironetin inhibitory activity. PMID:24761989

  14. Improved ligand binding energies derived from molecular dynamics: replicate sampling enhances the search of conformational space.

    Science.gov (United States)

    Adler, Marc; Beroza, Paul

    2013-08-26

    Does a single molecular trajectory provide an adequate sample conformational space? Our calculations indicate that for Molecular Mechanics--Poisson-Boltzmann Surface Area (MM-PBSA) measurement of protein ligand binding, a single molecular dynamics trajectory does not provide a representative sampling of phase space. For a single trajectory, the binding energy obtained by averaging over a number of molecular dynamics frames in an equilibrated system will converge after an adequate simulation time. A separate trajectory with nearly identical starting coordinates (1% randomly perturbed by 0.001 Å), however, can lead to a significantly different calculated binding energy. Thus, even though the calculated energy converges for a single molecular dynamics run, the variation across separate runs implies that a single run inadequately samples the system. The divergence in the trajectories is reflected in the individual energy components, such as the van der Waals and the electrostatics terms. These results indicate that the trajectories sample different conformations that are not in rapid exchange. Extending the length of the dynamics simulation does not resolve the energy differences observed between different trajectories. By averaging over multiple simulations, each with a nearly equivalent starting structure, we find the standard deviation in the calculated binding energy to be ∼1.3 kcal/mol. The work presented here indicates that combining MM-PBSA with multiple samples of the initial starting coordinates will produce more precise and accurate estimates of protein/ligand affinity. PMID:23845109

  15. Conformational polymorphism of the PrP106-126 peptide in different environments : A molecular dynamics study

    NARCIS (Netherlands)

    Villa, Alessandra; Mark, AE; Saracino, GAA; Cosentino, U; Pitea, D; Moro, G; Salmona, M

    2006-01-01

    Extensive molecular dynamic simulations (similar to 240 ns) have been used to investigate the conformational behavior of PrP106-126 prion peptide in four different environments (water, dimethyl sulfoxide, hexane, and trifluoroethanol) and under both neutral and acidic conditions. The conformational

  16. Ab initio computational studies on molecular conformation of N-methyl-glyphosate

    Science.gov (United States)

    Kaliannan, P.; Naseer Ali, M. Mohamed; Venuvanalingam, P.

    Conformational analysis of N-methyl-glyphosate has been carried out using an ab initio molecular orbital (MO) method at the HF/3-21G* levels of theory and the results are compared with the results of a previously studied compound, namely glyphosate. The potential energy surface of the molecule obtained by varying the central torsion angles (Φ, Ψ) was investigated in detail. Fourteen conformers with 5 kcal mol-1 energy cut-off have been selected from the potential energy surface for geometry optimization to locate the true minimum on the conformational space. The minimum has been found to be at (-62°, 110°) for the central torsion angles. This conformation is stabilized by hydrogen bond interactions (O-H···O and C-H···O) and the interactions due to protons nearer to each other. This cationic field leads to the formation of a hydrophobic patch in this structure, as well as in the structures closer to the global minimum. This patch may destabilize the favourable interaction of N-methyl-glyphosate with the surrounding amino acid residues in the binding cavity as they form the cationic field throughout the glyphosate binding region.

  17. Major Ampullate Spider Silk with Indistinguishable Spidroin Dope Conformations Leads to Different Fiber Molecular Structures

    Science.gov (United States)

    Dionne, Justine; Lefèvre, Thierry; Auger, Michèle

    2016-01-01

    To plentifully benefit from its properties (mechanical, optical, biological) and its potential to manufacture green materials, the structure of spider silk has to be known accurately. To this aim, the major ampullate (MA) silk of Araneus diadematus (AD) and Nephila clavipes (NC) has been compared quantitatively in the liquid and fiber states using Raman spectromicroscopy. The data show that the spidroin conformations of the two dopes are indistinguishable despite their specific amino acid composition. This result suggests that GlyGlyX and GlyProGlyXX amino acid motifs (X = Leu, Glu, Tyr, Ser, etc.) are conformationally equivalent due to the chain flexibility in the aqueous environment. Species-related sequence specificity is expressed more extensively in the fiber: the β-sheet content is lower and width of the orientation distribution of the carbonyl groups is broader for AD (29% and 58°, respectively) as compared to NC (37% and 51°, respectively). β-Sheet content values are close to the proportion of polyalanine segments, suggesting that β-sheet formation is mainly dictated by the spidroin sequence. The extent of molecular alignment seems to be related to the presence of proline (Pro) that may decrease conformational flexibility and inhibit chain extension and alignment upon drawing. It appears that besides the presence of Pro, secondary structure and molecular orientation contribute to the different mechanical properties of MA threads. PMID:27548146

  18. Imatinib (Gleevec@) conformations observed in single crystals, protein-Imatinib co-crystals and molecular dynamics: Implications for drug selectivity

    Science.gov (United States)

    Golzarroshan, B.; Siddegowda, M. S.; Li, Hong qi; Yathirajan, H. S.; Narayana, B.; Rathore, R. S.

    2012-06-01

    Structure and dynamics of the Leukemia drug, Imatinib, were examined using X-ray crystallography and molecular dynamics studies. Comparison of conformations observed in single crystals with several reported co-crystals of protein-drug complexes suggests existence of two conserved conformations of Imatinib, extended and compact (or folded), corresponding to two binding modes of interaction with the receptor. Furthermore, these conformations are conserved throughout a dynamics simulation. The present study attempts to draw a parallel on conformations and binding patterns of interactions, obtained from small-molecule single-crystal and macromolecule co-crystal studies, and provides structural insights for understanding the high selectivity of this drug molecule.

  19. Studies on the Conformational Features of Neomycin-B and its Molecular Recognition by RNA and Bacterial Defense Proteins

    Science.gov (United States)

    Asensio, Juan Luis; Bastida, Agatha; Jiménez-Barbero, Jesús

    According to NMR and molecular dynamics simulations, the conformational behavior of natural aminoglycosides is characterized by a remarkable flexibility, with different conformations, even non-exo-anomeric ones, in fast exchange. Very probably, this feature allows the adaptation of these ligands to the spatial and electronic requirements of different receptors. The large diversity of structures adopted by aminoglycosides in the binding pocket of the different RNA receptors and the distinct enzymes involved in bacterial resistance are consistent with this view. This conformational diversity can, in certain favorable cases, be exploited in the design of new antibiotic derivatives not susceptible to enzymatic inactivation, by designing tailor-made conformationally locked aminoglycosides.

  20. Designing molecular dynamics simulations to shift populations of the conformational states of calmodulin.

    Directory of Open Access Journals (Sweden)

    Ayse Ozlem Aykut

    Full Text Available We elucidate the mechanisms that lead to population shifts in the conformational states of calcium-loaded calmodulin (Ca(2+-CaM. We design extensive molecular dynamics simulations to classify the effects that are responsible for adopting occupied conformations available in the ensemble of NMR structures. Electrostatic interactions amongst the different regions of the protein and with its vicinal water are herein mediated by lowering the ionic strength or the pH. Amino acid E31, which is one of the few charged residues whose ionization state is highly sensitive to pH differences in the physiological range, proves to be distinctive in its control of population shifts. E31A mutation at low ionic strength results in a distinct change from an extended to a compact Ca(2+-CaM conformation within tens of nanoseconds, that otherwise occur on the time scales of microseconds. The kinked linker found in this particular compact form is observed in many of the target-bound forms of Ca(2+-CaM, increasing the binding affinity. This mutation is unique in controlling C-lobe dynamics by affecting the fluctuations between the EF-hand motif helices. We also monitor the effect of the ionic strength on the conformational multiplicity of Ca(2+-CaM. By lowering the ionic strength, the tendency of nonspecific anions in water to accumulate near the protein surface increases, especially in the vicinity of the linker. The change in the distribution of ions in the vicinal layer of water allows N- and C- lobes to span a wide variety of relative orientations that are otherwise not observed at physiological ionic strength. E31 protonation restores the conformations associated with physiological environmental conditions even at low ionic strength.

  1. DNA Conformational Variations Induced by Stretching 3'5'-Termini Studied by Molecular Dynamics Simulations

    Institute of Scientific and Technical Information of China (English)

    QI Wen-Peng; LEI Xiao-Ling

    2011-01-01

    @@ Investigating the interaction between protein and stretched DNA molecules has become a new way to study the protein DNA interaction.The conformations from different stretching methods give us a further understanding of the interaction between protein and DNA.We study the conformational variations of a 22-mer DNA caused by stretching both 3'-and 5'-termini by molecular dynamics simulations.It requires 250kJ/mol to stretch the DNA molecule by 3'5'-termini for 3.5 run and the force plateau is at 123.8 pN.The stretching 3'5'-termini leads to large values of the angle opening and the dihedral propeller between bases in one base pair, the double helix untwists from 34°to 20°and the successive base pairs rolls to the side of the DNA major groove.The distances between successive base pairs increases from 3.2.(A) to 5.6(A).%Investigating the interaction between protein and stretched DNA molecules has become a new way to study the protein DNA interaction. The conformations from different stretching methods give us a further understanding of the interaction between protein and DNA. We study the conformational variations of a 22-met DNA caused by stretching both 3'- and 5'-termini by molecular dynamics simulations. It requires 250k J/mol to stretch the DNA molecule by 3'5'-termini for 3.5nm and the force plateau is at 123.8pN. The stretching 3'5'-termini leads to large values of the angle opening and the dihedral propeller between bases in one base pair, the double helix untwists from 34° to 20° and the successive base pairs rolls to the side of the DNA major groove. The distances between successive base pairs increases from 3.2 (A) to 5.6 (A).

  2. Adsorption mechanisms of microcystin variant conformations at water-mineral interfaces: A molecular modeling investigation.

    Science.gov (United States)

    Pochodylo, Amy L; Aoki, Thalia G; Aristilde, Ludmilla

    2016-10-15

    Microcystins (MCs) are potent toxins released during cyanobacterial blooms. Clay minerals are implicated in trapping MCs within soil particles in surface waters and sediments. In the absence of molecular characterization, the relevance of previously proposed adsorption mechanisms is lacking. Towards obtaining this characterization, we conducted Monte Carlo simulations combined with molecular dynamics relaxation of two MC variants, MC-leucine-arginine (MC-LR) and MC-leucine-alanine (MC-LA), adsorbed on hydrated montmorillonite with different electrolytes. The resulting adsorbate structures revealed how MC conformations and aqueous conditions dictate binding interactions at the mineral surface. Electrostatic coupling between the arginine residue and a carboxylate in MC-LR excluded the participation of arginine in mediating adsorption on montmorillonite in a NaCl solution. However, in a CaCl2 solution, the complexation of Ca by two carboxylate moieties in MC-LR changed the MC conformation, which allowed arginine to mediate electrostatic interaction with the mineral. By contrast, due to the lack of arginine in MC-LA, complexation of Ca by only one carboxylate in MC-LA was required to favor Ca-bridging interaction with the mineral. Multiple water-bridged H-bonding interactions were also important in anchoring MCs at the mineral surface. Our modeling results offer molecular insights into the structural and chemical factors that can control the fate of MCs at water-mineral interfaces. PMID:27433998

  3. Adsorption mechanisms of microcystin variant conformations at water-mineral interfaces: A molecular modeling investigation.

    Science.gov (United States)

    Pochodylo, Amy L; Aoki, Thalia G; Aristilde, Ludmilla

    2016-10-15

    Microcystins (MCs) are potent toxins released during cyanobacterial blooms. Clay minerals are implicated in trapping MCs within soil particles in surface waters and sediments. In the absence of molecular characterization, the relevance of previously proposed adsorption mechanisms is lacking. Towards obtaining this characterization, we conducted Monte Carlo simulations combined with molecular dynamics relaxation of two MC variants, MC-leucine-arginine (MC-LR) and MC-leucine-alanine (MC-LA), adsorbed on hydrated montmorillonite with different electrolytes. The resulting adsorbate structures revealed how MC conformations and aqueous conditions dictate binding interactions at the mineral surface. Electrostatic coupling between the arginine residue and a carboxylate in MC-LR excluded the participation of arginine in mediating adsorption on montmorillonite in a NaCl solution. However, in a CaCl2 solution, the complexation of Ca by two carboxylate moieties in MC-LR changed the MC conformation, which allowed arginine to mediate electrostatic interaction with the mineral. By contrast, due to the lack of arginine in MC-LA, complexation of Ca by only one carboxylate in MC-LA was required to favor Ca-bridging interaction with the mineral. Multiple water-bridged H-bonding interactions were also important in anchoring MCs at the mineral surface. Our modeling results offer molecular insights into the structural and chemical factors that can control the fate of MCs at water-mineral interfaces.

  4. Probing the bioactivity-relevant chemical space of robust reactions and common molecular building blocks.

    Science.gov (United States)

    Hartenfeller, Markus; Eberle, Martin; Meier, Peter; Nieto-Oberhuber, Cristina; Altmann, Karl-Heinz; Schneider, Gisbert; Jacoby, Edgar; Renner, Steffen

    2012-05-25

    In the search for new bioactive compounds, there is a trend toward increasingly complex compound libraries aiming to target the demanding targets of the future. In contrast, medicinal chemistry and traditional library design rely mainly on a small set of highly established and robust reactions. Here, we probe a set of 58 such reactions for their ability to sample the chemical space of known bioactive molecules, and the potential to create new scaffolds. Combined with ~26,000 common available building blocks, the reactions retrieve around 9% of a scaffold-diverse set of compounds active on human target proteins covering all major pharmaceutical target classes. Almost 80% of generated scaffolds from virtual one-step synthesis products are not present in a large set of known bioactive molecules for human targets, indicating potential for new discoveries. The results suggest that established synthesis resources are well suited to cover the known bioactivity-relevant chemical space and that there are plenty of unexplored regions accessible by these reactions, possibly providing valuable "low-hanging fruit" for hit discovery. PMID:22512717

  5. New binding site conformations of the dengue virus NS3 protease accessed by molecular dynamics simulation.

    Directory of Open Access Journals (Sweden)

    Hugo de Almeida

    Full Text Available Dengue fever is caused by four distinct serotypes of the dengue virus (DENV1-4, and is estimated to affect over 500 million people every year. Presently, there are no vaccines or antiviral treatments for this disease. Among the possible targets to fight dengue fever is the viral NS3 protease (NS3PRO, which is in part responsible for viral processing and replication. It is now widely recognized that virtual screening campaigns should consider the flexibility of target protein by using multiple active conformational states. The flexibility of the DENV NS3PRO could explain the relatively low success of previous virtual screening studies. In this first work, we explore the DENV NS3PRO conformational states obtained from molecular dynamics (MD simulations to take into account protease flexibility during the virtual screening/docking process. To do so, we built a full NS3PRO model by multiple template homology modeling. The model comprised the NS2B cofactor (essential to the NS3PRO activation, a glycine flexible link and the proteolytic domain. MD simulations had the purpose to sample, as closely as possible, the ligand binding site conformational landscape prior to inhibitor binding. The obtained conformational MD sample was clustered into four families that, together with principal component analysis of the trajectory, demonstrated protein flexibility. These results allowed the description of multiple binding modes for the Bz-Nle-Lys-Arg-Arg-H inhibitor, as verified by binding plots and pair interaction analysis. This study allowed us to tackle protein flexibility in our virtual screening campaign against the dengue virus NS3 protease.

  6. Conformational flexibility of β-secretase:molecular dynamics simulation and essential dynamics analysis

    Institute of Scientific and Technical Information of China (English)

    Bing XIONG; Xiao-qin HUANG; Ling-ling SHEN; Jian-hua SHEN; Xiao-min LUO; Xu SHEN; Hua-liang JIANG; Kai-xian CHEN

    2004-01-01

    AIM: Based on the structural analysis to reveal the mechanism of ligand binding to β-secretase and the specificity of each binding sub-site. METHODS: Molecular dynamics was used to simulate on the ligand free β-secretase and ligand bound β-secretase. The trajectories were analyzed using the essential dynamics, and the significant conformational change was illustrated employing the DynDom program. RESULTS: The essential dynamics and DynDom analyses clearly showed that the β-secretase experienced a large conformational change upon the substrate or inhibitor binding. The flap structure adopted a swing motion, gradually covering the active site to facilitate the ligand binding process. Residues Ser86 and Ile87 served as the hinge point. Inhibitor-enzyme interaction analysis revealed that residues at P2, Pl, and P1' positions of the inhibitor were very important for the binding, and residues at P2' and P3' positions may be modified to improve the binding specificity. S3 subsite of the enzyme still had space to modify the inhibitors in increasing the binding affinity. CONCLUSION: The information presented here is valuable and could be used to identify small molecular inhibitors of β-secretase.

  7. Impact of molecular weight on the formation of electrosprayed chitosan microcapsules as delivery vehicles for bioactive compounds.

    Science.gov (United States)

    Gómez-Mascaraque, Laura G; Sanchez, Gloria; López-Rubio, Amparo

    2016-10-01

    The molecular weight of chitosan is one of its most determinant characteristics, which affects its processability and its performance as a biomaterial. However, information about the effect of this parameter on the formation of electrosprayed chitosan microcapsules is scarce. In this work, the impact of chitosan molecular weight on its electrosprayability was studied and correlated with its effect on the viscosity, surface tension and electrical conductivity of solutions. A Discriminant Function Analysis revealed that the morphology of the electrosprayed chitosan materials could be correctly predicted using these three parameters for almost 85% of the samples. The suitability of using electrosprayed chitosan capsules as carriers for bioactive agents was also assessed by loading them with a model active compound, (-)-epigallocatechin gallate (EGCG). This encapsulation, with an estimated efficiency of around 80% in terms of preserved antioxidant activity, showed the potential to prolong the antiviral activity of EGCG against murine norovirus via gradual bioactive release combined with its protection against degradation in simulated physiological conditions. PMID:27312621

  8. Earle K. Plyler Prize for Molecular Spectroscopy and Dynamics Lecture: 2D IR Spectroscopy of Peptide Conformation

    Science.gov (United States)

    Tokmakoff, Andrei

    2012-02-01

    Descriptions of protein and peptide conformation are colored by the methods we use to study them. Protein x-ray and NMR structures often lead to impressions of rigid or well-defined conformations, even though these are dynamic molecules. The conformational fluctuations and disorder of proteins and peptides is more difficult to quantify. This presentation will describe an approach toward characterizing and quantifying structural heterogeneity and disorder in peptides using 2D IR spectroscopy. Using amide I vibrational spectroscopy, isotope labeling strategies, and computational modeling based on molecular dynamics simulations and Markov state models allows us to characterize distinct peptide conformers and conformational variation. The examples illustrated include the beta-hairpin tripzip2 and elastin-like peptides.

  9. Folding simulations of gramicidin A into the β-helix conformations: Simulated annealing molecular dynamics study

    Science.gov (United States)

    Mori, Takaharu; Okamoto, Yuko

    2009-10-01

    Gramicidin A is a linear hydrophobic 15-residue peptide which consists of alternating D- and L-amino acids and forms a unique tertiary structure, called the β6.3-helix, to act as a cation-selective ion channel in the natural conditions. In order to investigate the intrinsic ability of the gramicidin A monomer to form secondary structures, we performed the folding simulation of gramicidin A using a simulated annealing molecular dynamics (MD) method in vacuum mimicking the low-dielectric, homogeneous membrane environment. The initial conformation was a fully extended one. From the 200 different MD runs, we obtained a right-handed β4.4-helix as the lowest-potential-energy structure, and left-handed β4.4-helix, right-handed and left-handed β6.3-helix as local-minimum energy states. These results are in accord with those of the experiments of gramicidin A in homogeneous organic solvent. Our simulations showed a slight right-hand sense in the lower-energy conformations and a quite β-sheet-forming tendency throughout almost the entire sequence. In order to examine the stability of the obtained right-handed β6.3-helix and β4.4-helix structures in more realistic membrane environment, we have also performed all-atom MD simulations in explicit water, ion, and lipid molecules, starting from these β-helix structures. The results suggested that β6.3-helix is more stable than β4.4-helix in the inhomogeneous, explicit membrane environment, where the pore water and the hydrogen bonds between Trp side-chains and lipid-head groups have a role to further stabilize the β6.3-helix conformation.

  10. Conformational Search on the Lewis X Structure by Molecular Dynamic: Study of Tri- and Pentasaccharide

    Directory of Open Access Journals (Sweden)

    N. Khebichat

    2012-01-01

    Full Text Available Carbohydrates play vital roles in many biological processes, such as recognition, adhesion, and signalling between cells. The Lewis X determinant is a trisaccharide fragment implicated as a specific differentiation antigen, tumor antigen, and key component of the ligand for the endothelial leukocyte adhesion molecule, so it is necessary or essential to determine and to know their conformational and structural properties. In this work, conformational analysis was performed using molecular dynamics (MD simulation with the AMBER10 program package in order to study the dynamic behavior of of the Lewis X trisaccharide (β-D-Gal-(1,4-[α-L-Fuc-(1,3]-β-D-GlcNAc-OMe and the Lewis X pentasaccharide (β-D-Gal-(1,4-[α-L-Fuc-(1,3]-β-D-GlcNAc-(1,3-β-D-Gal-(1,4-β-D-Glu-OMe in explicit water model at 300 K for 10 ns using the GLYCAM 06 force field.

  11. Molecular identification of Amazonian stingless bees using polymerase chain reaction single-strand conformation polymorphism.

    Science.gov (United States)

    Souza, M T; Carvalho-Zilse, G A

    2014-01-01

    In countries containing a mega diversity of wildlife, such as Brazil, identifying and characterizing biological diversity is a continuous process for the scientific community, even in face of technological and scientific advances. This activity demands initiatives for the taxonomic identification of highly diverse groups, such as stingless bees, including molecular analysis strategies. This type of bee is distributed in all of the Brazilian states, with the highest species diversity being found in the State of Amazônia. However, the estimated number of species diverges among taxonomists. These bees are considered the main pollinators in the Amazon rainforest, in which they obtain food and shelter; however, their persistence is constantly threatened by deforestation pressure. Hence, it is important to classify the number and abundance of bee specie, to measure their decline and implement meaningful, priority conservation strategies. This study aims to maximize the implementation of more direct, economic and successful techniques for the taxonomic identification of stingless bees. Specifically, the genes 16S rRNA and COI from mitochondrial DNA were used as molecular markers to differentiate 9 species of Amazonian stingless bees based on DNA polymorphism, using the polymerase chain reaction-single-strand conformation polymorphism technique. We registered different, exclusive SSCP haplotypes for both genes in all species analyzed. These results demonstrate that SSCP is a simple and cost-effective technique that is applicable to the molecular identification of stingless bee species. PMID:25117306

  12. Influence of Molecular Conformations and Microstructure on the Optoelectronic Properties of Conjugated Polymers

    Directory of Open Access Journals (Sweden)

    Ioan Botiz

    2014-03-01

    Full Text Available It is increasingly obvious that the molecular conformations and the long-range arrangement that conjugated polymers can adopt under various experimental conditions in bulk, solutions or thin films, significantly impact their resulting optoelectronic properties. As a consequence, the functionalities and efficiencies of resulting organic devices, such as field-effect transistors, light-emitting diodes, or photovoltaic cells, also dramatically change due to the close structure/property relationship. A range of structure/optoelectronic properties relationships have been investigated over the last few years using various experimental and theoretical methods, and, further, interesting correlations are continuously revealed by the scientific community. In this review, we discuss the latest findings related to the structure/optoelectronic properties interrelationships that exist in organic devices fabricated with conjugated polymers in terms of charge mobility, absorption, photoluminescence, as well as photovoltaic properties.

  13. Influence of Molecular Conformations and Microstructure on the Optoelectronic Properties of Conjugated Polymers

    KAUST Repository

    Botiz, Ioan

    2014-03-19

    It is increasingly obvious that the molecular conformations and the long-range arrangement that conjugated polymers can adopt under various experimental conditions in bulk, solutions or thin films, significantly impact their resulting optoelectronic properties. As a consequence, the functionalities and efficiencies of resulting organic devices, such as field-effect transistors, light-emitting diodes, or photovoltaic cells, also dramatically change due to the close structure/property relationship. A range of structure/optoelectronic properties relationships have been investigated over the last few years using various experimental and theoretical methods, and, further, interesting correlations are continuously revealed by the scientific community. In this review, we discuss the latest findings related to the structure/optoelectronic properties interrelationships that exist in organic devices fabricated with conjugated polymers in terms of charge mobility, absorption, photoluminescence, as well as photovoltaic properties. © 2014 by the authors.

  14. Conformational Melding Permits a Conserved Binding Geometry in TCR Recognition of Foreign and Self Molecular Mimics

    Energy Technology Data Exchange (ETDEWEB)

    Borbulevych, Oleg Y.; Piepenbrink, Kurt H.; Baker, Brian M. (Notre)

    2012-03-16

    Molecular mimicry between foreign and self Ags is a mechanism of TCR cross-reactivity and is thought to contribute to the development of autoimmunity. The {alpha}{beta} TCR A6 recognizes the foreign Ag Tax from the human T cell leukemia virus-1 when presented by the class I MHC HLA-A2. In a possible link with the autoimmune disease human T cell leukemia virus-1-associated myelopathy/tropical spastic paraparesis, A6 also recognizes a self peptide from the neuronal protein HuD in the context of HLA-A2. We found in our study that the complexes of the HuD and Tax epitopes with HLA-A2 are close but imperfect structural mimics and that in contrast with other recent structures of TCRs with self Ags, A6 engages the HuD Ag with the same traditional binding mode used to engage Tax. Although peptide and MHC conformational changes are needed for recognition of HuD but not Tax and the difference of a single hydroxyl triggers an altered TCR loop conformation, TCR affinity toward HuD is still within the range believed to result in negative selection. Probing further, we found that the HuD-HLA-A2 complex is only weakly stable. Overall, these findings help clarify how molecular mimicry can drive self/nonself cross-reactivity and illustrate how low peptide-MHC stability can permit the survival of T cells expressing self-reactive TCRs that nonetheless bind with a traditional binding mode.

  15. PubChem3D: Conformer generation

    Directory of Open Access Journals (Sweden)

    Bolton Evan E

    2011-01-01

    Full Text Available Abstract Background PubChem, an open archive for the biological activities of small molecules, provides search and analysis tools to assist users in locating desired information. Many of these tools focus on the notion of chemical structure similarity at some level. PubChem3D enables similarity of chemical structure 3-D conformers to augment the existing similarity of 2-D chemical structure graphs. It is also desirable to relate theoretical 3-D descriptions of chemical structures to experimental biological activity. As such, it is important to be assured that the theoretical conformer models can reproduce experimentally determined bioactive conformations. In the present study, we investigate the effects of three primary conformer generation parameters (the fragment sampling rate, the energy window size, and force field variant upon the accuracy of theoretical conformer models, and determined optimal settings for PubChem3D conformer model generation and conformer sampling. Results Using the software package OMEGA from OpenEye Scientific Software, Inc., theoretical 3-D conformer models were generated for 25,972 small-molecule ligands, whose 3-D structures were experimentally determined. Different values for primary conformer generation parameters were systematically tested to find optimal settings. Employing a greater fragment sampling rate than the default did not improve the accuracy of the theoretical conformer model ensembles. An ever increasing energy window did increase the overall average accuracy, with rapid convergence observed at 10 kcal/mol and 15 kcal/mol for model building and torsion search, respectively; however, subsequent study showed that an energy threshold of 25 kcal/mol for torsion search resulted in slightly improved results for larger and more flexible structures. Exclusion of coulomb terms from the 94s variant of the Merck molecular force field (MMFF94s in the torsion search stage gave more accurate conformer models at

  16. Molecular modeling methods in the study and design of bioactive compounds: An introduction [Métodos de Modelagem Molecular para estudo e planejamento de compostos bioativos: Uma introdução

    OpenAIRE

    Carlos Mauricio R. Sant´Anna

    2009-01-01

    This paper presents an introduction to the main methods used in molecular modeling calculations applied in the design of bioactive compounds. An introductory description of the two approaches methods predominantly used in molecular modeling studies is presented: the classical approach, which includes molecular mechanics and molecular dynamics; and the quantum mechanical approach, which includes ab initio and semi-empirical methods. We discuss how these methods can be applied to determine the ...

  17. Mechanism of Mcl-1 Conformational Regulation Upon Small Molecule Binding Revealed by Molecular Dynamic Simulation.

    Science.gov (United States)

    Wang, Anhui; Song, Ting; Wang, Ziqian; Liu, Yubo; Fan, Yudan; Zhang, Yahui; Zhang, Zhichao

    2016-04-01

    Inhibition of interactions between Mcl-1 and proapoptotic proteins is considered to be a therapeutic strategy to induce apoptosis in cancer cells. Here, we adopted molecular dynamics simulation with molecular mechanics-Poisson Boltzmann/surface area method (MM-PB/SA) to study the inhibition mechanism of three Mcl-1 inhibitors, compounds 1, 2 and 3. Analysis of energy components shows that the better binding free energy of compound 3 than compounds 1 and 2 is attributable to the van der Waals energy (ΔEvdw ) and non-polar solvation energy (ΔGnp ) upon binding. In addition to the excellent agreement with previous experimentally determined affinities, our simulation results further show a bend of helix 4 on Mcl-1 upon compound 3 binding, which is driven by hydrophobic interaction with residue Val(253) , leading to a narrowed BH3-binding groove to impede Puma(BH) (3) binding. The computational result is consistent with our competitive isothermal titration calorimetry (ITC) assays, which shows that the competitive ability of compound 3 toward Mcl-1/Puma(BH) (3) complex is improved beyond its direct binding affinity toward Mcl-1 itself, and compound 3 exhibits much more efficiency to compete with Puma(BH) (3) than compound 2. Our study provides a new strategy to improve inhibitory activity on Mcl-1 based on the conformational dynamic change. PMID:26518611

  18. Towards a Molecular Understanding of the Link between Imatinib Resistance and Kinase Conformational Dynamics.

    Directory of Open Access Journals (Sweden)

    Silvia Lovera

    2015-11-01

    Full Text Available Due to its inhibition of the Abl kinase domain in the BCR-ABL fusion protein, imatinib is strikingly effective in the initial stage of chronic myeloid leukemia with more than 90% of the patients showing complete remission. However, as in the case of most targeted anti-cancer therapies, the emergence of drug resistance is a serious concern. Several drug-resistant mutations affecting the catalytic domain of Abl and other tyrosine kinases are now known. But, despite their importance and the adverse effect that they have on the prognosis of the cancer patients harboring them, the molecular mechanism of these mutations is still debated. Here by using long molecular dynamics simulations and large-scale free energy calculations complemented by in vitro mutagenesis and microcalorimetry experiments, we model the effect of several widespread drug-resistant mutations of Abl. By comparing the conformational free energy landscape of the mutants with those of the wild-type tyrosine kinases we clarify their mode of action. It involves significant and complex changes in the inactive-to-active dynamics and entropy/enthalpy balance of two functional elements: the activation-loop and the conserved DFG motif. What is more the T315I gatekeeper mutant has a significant impact on the binding mechanism itself and on the binding kinetics.

  19. Towards a Molecular Understanding of the Link between Imatinib Resistance and Kinase Conformational Dynamics.

    Science.gov (United States)

    Lovera, Silvia; Morando, Maria; Pucheta-Martinez, Encarna; Martinez-Torrecuadrada, Jorge L; Saladino, Giorgio; Gervasio, Francesco L

    2015-11-01

    Due to its inhibition of the Abl kinase domain in the BCR-ABL fusion protein, imatinib is strikingly effective in the initial stage of chronic myeloid leukemia with more than 90% of the patients showing complete remission. However, as in the case of most targeted anti-cancer therapies, the emergence of drug resistance is a serious concern. Several drug-resistant mutations affecting the catalytic domain of Abl and other tyrosine kinases are now known. But, despite their importance and the adverse effect that they have on the prognosis of the cancer patients harboring them, the molecular mechanism of these mutations is still debated. Here by using long molecular dynamics simulations and large-scale free energy calculations complemented by in vitro mutagenesis and microcalorimetry experiments, we model the effect of several widespread drug-resistant mutations of Abl. By comparing the conformational free energy landscape of the mutants with those of the wild-type tyrosine kinases we clarify their mode of action. It involves significant and complex changes in the inactive-to-active dynamics and entropy/enthalpy balance of two functional elements: the activation-loop and the conserved DFG motif. What is more the T315I gatekeeper mutant has a significant impact on the binding mechanism itself and on the binding kinetics.

  20. Biophysical exploration of protein-flavonol recognition: effects of molecular properties and conformational flexibility.

    Science.gov (United States)

    Ding, Fei; Peng, Wei; Peng, Yu-Kui

    2016-04-28

    The current work explores the biomolecular recognition of a series of flavonols by a protein and then uncovers the influences of the structural features of flavonols and the protein's own characteristics, e.g. the dynamics and flexibility, on the bioavailability of flavonols by using the pivotal biomacromolecule hemoglobin as a model. The experimental results revealed that flavonol may lead to a notable decrease in the steady-state fluorescence intensity of the β-37 Trp residue, and in the meantime the R-T transition of the protein transpired. Such noncovalent recognition forms the ground-state adduct, with an association intensity of 3.991 × 10(4) M(-1) in the reaction process, which has already been authenticated by the detailed analysis of time-resolved fluorescence and UV/vis absorption spectra. Furthermore, flavonol can form hydrogen bonds and π-conjugation effects with several amino acid residues on the polypeptide chain, for example, Trp-37, Arg-40, Asp-99 and Asn-102, and this event would induce self-regulation of the compact, regular conformation of the protein to a certain extent, which explicitly corroborates the results of circular dichroism. According to the study of molecular docking and structure-activity relationships, we could see that the recognition capacities of the protein-flavonols are inversely interrelated with the C log P values of the flavonol molecules. Moreover, the properties of the substituents in the structural B-ring unit of flavonols, i.e. polarity, position and number, will also prominently affect the degree of affinity and bioavailability of the protein-flavonol complexes. The analytical results of molecular dynamics (MD) simulation testified that the discussions of the structure-activity relationships are entirely logical, and the conformations of the amino acid residues forming noncovalent interactions tend to be stable in the MD simulation, as further elucidated from the dynamics data. Plainly, molecular recognition of

  1. Molecular characteristics of humic acids isolated from vermicomposts and their relationship to bioactivity.

    Science.gov (United States)

    Martinez-Balmori, Dariellys; Spaccini, Riccardo; Aguiar, Natália Oliveira; Novotny, Etelvino Henrique; Olivares, Fábio Lopes; Canellas, Luciano Pasqualoto

    2014-11-26

    Vermitechnology is an effective composting method, which transforms biomass into nutrient-rich organic fertilizer. Mature vermicompost is a renewable organic product containing humic substances with high biological activity. The aim of this study was to assess the chemical characteristics and the bioactivity of humic acids isolated from different vermicomposts produced with either cattle manure, sugar cane bagasse, sunflower cake from seed oil extraction, or filter cake from a sugar cane factory. More than 200 different molecules were found, and it was possible to identify chemical markers on humic acids according to the nature of the organic source. The large hydrophobic character of humic extracts and the preservation of altered lignin derivatives confer to humic acids the ability to induce lateral root emergence in maize seedlings. Humic acid-like substances extracted from plant biomass residues represent an additional valuable product of vermicomposting that can be used as a plant growth promoter. PMID:25379603

  2. Molecular characteristics of humic acids isolated from vermicomposts and their relationship to bioactivity.

    Science.gov (United States)

    Martinez-Balmori, Dariellys; Spaccini, Riccardo; Aguiar, Natália Oliveira; Novotny, Etelvino Henrique; Olivares, Fábio Lopes; Canellas, Luciano Pasqualoto

    2014-11-26

    Vermitechnology is an effective composting method, which transforms biomass into nutrient-rich organic fertilizer. Mature vermicompost is a renewable organic product containing humic substances with high biological activity. The aim of this study was to assess the chemical characteristics and the bioactivity of humic acids isolated from different vermicomposts produced with either cattle manure, sugar cane bagasse, sunflower cake from seed oil extraction, or filter cake from a sugar cane factory. More than 200 different molecules were found, and it was possible to identify chemical markers on humic acids according to the nature of the organic source. The large hydrophobic character of humic extracts and the preservation of altered lignin derivatives confer to humic acids the ability to induce lateral root emergence in maize seedlings. Humic acid-like substances extracted from plant biomass residues represent an additional valuable product of vermicomposting that can be used as a plant growth promoter.

  3. Probing the conformation of FhaC with small-angle neutron scattering and molecular modeling.

    Science.gov (United States)

    Gabel, Frank; Lensink, Marc F; Clantin, Bernard; Jacob-Dubuisson, Françoise; Villeret, Vincent; Ebel, Christine

    2014-07-01

    Probing the solution structure of membrane proteins represents a formidable challenge, particularly when using small-angle scattering. Detergent molecules often present residual scattering contributions even at their match point in small-angle neutron scattering (SANS) measurements. Here, we studied the conformation of FhaC, the outer-membrane, β-barrel transporter of the Bordetella pertussis filamentous hemagglutinin adhesin. SANS measurements were performed on homogeneous solutions of FhaC solubilized in n-octyl-d17-βD-glucoside and on a variant devoid of the α helix H1, which critically obstructs the FhaC pore, in two solvent conditions corresponding to the match points of the protein and the detergent, respectively. Protein-bound detergent amounted to 142 ± 10 mol/mol as determined by analytical ultracentrifugation. By using molecular modeling and starting from three distinct conformations of FhaC and its variant embedded in lipid bilayers, we generated ensembles of protein-detergent arrangement models with 120-160 detergent molecules. The scattered curves were back-calculated for each model and compared with experimental data. Good fits were obtained for relatively compact, connected detergent belts, which occasionally displayed small detergent-free patches on the outer surface of the β barrel. The combination of SANS and modeling clearly enabled us to infer the solution structure of FhaC, with H1 inside the pore as in the crystal structure. We believe that our strategy of combining explicit atomic detergent modeling with SANS measurements has significant potential for structural studies of other detergent-solubilized membrane proteins. PMID:24988353

  4. Conformations of some lower-size large-ring cyclodextrins derived from conformational search with molecular dynamics and principal component analysis

    Science.gov (United States)

    Ivanov, Petko

    2012-02-01

    Computational studies were conducted on the conformations of some lower-size large-ring cyclodextrins, CDn (n = 11, 12, 13, 15, 16, 17). Principal component analysis (PCA) was applied for post-processing of trajectories from conformational search based on 100.0 ns molecular dynamics (MD) simulations. The dominant PCA modes for concerted motions of the macroring atoms were monitored in a lower-dimensions subspace. The first six lowest indexed principal components contribute more than 90% of the total atomic motions in all cases, with about 70% (CD12) to 90% (CD17) contribution coming from the three highest-eigenvalue principal components. Representative average geometries of the cyclodextrin macrorings were also obtained for the whole simulation and for the ten 10.0 ns time intervals of the simulation. We concluded that the whole set of structures could be sorted into two clearly distinguished groups, separated by the figure-eight conformation of CD14: (i) open bent boat-like macrorings (CD11 to CD13), and (ii) two winded single helical strands (an anti-parallel double helix with foldbacks at each end), CD15 to CD17, shaped as number eight for the odd-number-residues cases, CD15 and CD17. CD13 and CD14 mark the borderline between lower and higher flexibilities of the lower-size LR-CDs macrorings.

  5. Molecular effects of bioactive fraction of Curcuma mangga (DLBS4847) as a downregulator of 5α-reductase activity pathways in prostatic epithelial cells

    OpenAIRE

    TJANDRAWINATA, Raymond; Karsono, Agung Heru; Tandrasasmita,Olivia

    2014-01-01

    Agung Heru Karsono, Olivia Mayasari Tandrasasmita, Raymond R TjandrawinataSection of Molecular Pharmacology, Research Innovation and Invention, Dexa Laboratories of Biomolecular Sciences, Dexa Medica, Cikarang, IndonesiaAbstract: DLBS4847 is a standardized bioactive fraction of Curcuma mangga. In this study, we used prostate cancer (PC)-3 as the cell line to study the effects of DLBS4847 on prostatic cell viability, as well as related molecular changes associated with the decreased cell numbe...

  6. DG-AMMOS: A New tool to generate 3D conformation of small molecules using Distance Geometry and Automated Molecular Mechanics Optimization for in silico Screening

    Directory of Open Access Journals (Sweden)

    Villoutreix Bruno O

    2009-11-01

    Full Text Available Abstract Background Discovery of new bioactive molecules that could enter drug discovery programs or that could serve as chemical probes is a very complex and costly endeavor. Structure-based and ligand-based in silico screening approaches are nowadays extensively used to complement experimental screening approaches in order to increase the effectiveness of the process and facilitating the screening of thousands or millions of small molecules against a biomolecular target. Both in silico screening methods require as input a suitable chemical compound collection and most often the 3D structure of the small molecules has to be generated since compounds are usually delivered in 1D SMILES, CANSMILES or in 2D SDF formats. Results Here, we describe the new open source program DG-AMMOS which allows the generation of the 3D conformation of small molecules using Distance Geometry and their energy minimization via Automated Molecular Mechanics Optimization. The program is validated on the Astex dataset, the ChemBridge Diversity database and on a number of small molecules with known crystal structures extracted from the Cambridge Structural Database. A comparison with the free program Balloon and the well-known commercial program Omega generating the 3D of small molecules is carried out. The results show that the new free program DG-AMMOS is a very efficient 3D structure generator engine. Conclusion DG-AMMOS provides fast, automated and reliable access to the generation of 3D conformation of small molecules and facilitates the preparation of a compound collection prior to high-throughput virtual screening computations. The validation of DG-AMMOS on several different datasets proves that generated structures are generally of equal quality or sometimes better than structures obtained by other tested methods.

  7. Molecular dynamics analysis of conformational change of paramyxovirus F protein during the initial steps of membrane fusion

    Energy Technology Data Exchange (ETDEWEB)

    Martin-Garcia, Fernando; Mendieta-Moreno, Jesus Ignacio; Mendieta, Jesus [Centro de Biologia Molecular ' Severo Ochoa' (CSIC/UAM), C/ Nicolas Cabrera, 1, Cantoblanco, 28049 Madrid (Spain); Biomol-Informatics SL, Parque Cientifico de Madrid, C/ Faraday, 7, Cantoblanco, 28049 Madrid (Spain); Gomez-Puertas, Paulino, E-mail: pagomez@cbm.uam.es [Centro de Biologia Molecular ' Severo Ochoa' (CSIC/UAM), C/ Nicolas Cabrera, 1, Cantoblanco, 28049 Madrid (Spain)

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer Initial conformational change of paramyxovirus F protein is caused only by mechanical forces. Black-Right-Pointing-Pointer HRA region undergoes a structural change from a beta + alpha conformation to an extended coil and then to an all-alpha conformation. Black-Right-Pointing-Pointer HRS domains of F protein form three single {alpha}-helices prior to generation of the coiled coil. -- Abstract: The fusion of paramyxovirus to the cell membrane is mediated by fusion protein (F protein) present in the virus envelope, which undergoes a dramatic conformational change during the process. Unlike hemagglutinin in orthomyxovirus, this change is not mediated by an alteration of environmental pH, and its cause remains unknown. Steered molecular dynamics analysis leads us to suggest that the conformational modification is mediated only by stretching mechanical forces once the transmembrane fusion peptide of the protein is anchored to the cell membrane. Such elongating forces will generate major secondary structure rearrangement in the heptad repeat A region of the F protein; from {beta}-sheet conformation to an elongated coil and then spontaneously to an {alpha}-helix. In addition, it is proposed that the heptad repeat A region adopts a final three-helix coiled coil and that this structure appears after the formation of individual helices in each monomer.

  8. Quantitatively integrating molecular structure and bioactivity profile evidence into drug-target relationship analysis

    Directory of Open Access Journals (Sweden)

    Xu Tianlei

    2012-05-01

    Full Text Available Abstract Background Public resources of chemical compound are in a rapid growth both in quantity and the types of data-representation. To comprehensively understand the relationship between the intrinsic features of chemical compounds and protein targets is an essential task to evaluate potential protein-binding function for virtual drug screening. In previous studies, correlations were proposed between bioactivity profiles and target networks, especially when chemical structures were similar. With the lack of effective quantitative methods to uncover such correlation, it is demanding and necessary for us to integrate the information from multiple data sources to produce an comprehensive assessment of the similarity between small molecules, as well as quantitatively uncover the relationship between compounds and their targets by such integrated schema. Results In this study a multi-view based clustering algorithm was introduced to quantitatively integrate compound similarity from both bioactivity profiles and structural fingerprints. Firstly, a hierarchy clustering was performed with the fused similarity on 37 compounds curated from PubChem. Compared to clustering in a single view, the overall common target number within fused classes has been improved by using the integrated similarity, which indicated that the present multi-view based clustering is more efficient by successfully identifying clusters with its members sharing more number of common targets. Analysis in certain classes reveals that mutual complement of the two views for compound description helps to discover missing similar compound when only single view was applied. Then, a large-scale drug virtual screen was performed on 1267 compounds curated from Connectivity Map (CMap dataset based on the fused similarity, which obtained a better ranking result compared to that of single-view. These comprehensive tests indicated that by combining different data representations; an improved

  9. On the connection between nonmonotonic taste behavior and molecular conformation in solution: The case of rebaudioside-A

    International Nuclear Information System (INIS)

    The diterpene steviol glycoside, rebaudioside A, is a natural high potency non-caloric sweetener extracted from the leaves of Stevia rebaudiana. This compound shows a parabolic change in sweet taste intensity with temperature which contrasts with the general finding for other synthetic or natural sweeteners whose sweet taste increases with temperature. The nonmonotonic taste behavior was determined by sensory analysis using large taste panels. The conformational landscape of rebaudioside A was established at a range of temperatures by means of nuclear magnetic resonance and molecular dynamics simulation. The relationship between various conformations and the observed sweetness of rebaudioside A is described

  10. On the connection between nonmonotonic taste behavior and molecular conformation in solution: The case of rebaudioside-A

    Energy Technology Data Exchange (ETDEWEB)

    Chopade, Prashant D.; Sarma, Bipul; Santiso, Erik E.; Chen, Jie; Trout, Bernhardt L.; Myerson, Allan S., E-mail: myerson@mit.edu [Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 66-568, Cambridge, Massachusetts 02139 (United States); Simpson, Jeffrey [Department of Chemistry Instrumentation Facility, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 18-0090, Cambridge, Massachusetts 02139 (United States); Fry, John C.; Biermann, Kari L. [Connect Consulting, 6 Hollands Field, Horsham RH123HQ (United Kingdom); Yurttas, Nese [Cargill, Inc., Global Food Technology, 2301 Crosby Road, Wayzata, Minnesota 55391 (United States)

    2015-12-28

    The diterpene steviol glycoside, rebaudioside A, is a natural high potency non-caloric sweetener extracted from the leaves of Stevia rebaudiana. This compound shows a parabolic change in sweet taste intensity with temperature which contrasts with the general finding for other synthetic or natural sweeteners whose sweet taste increases with temperature. The nonmonotonic taste behavior was determined by sensory analysis using large taste panels. The conformational landscape of rebaudioside A was established at a range of temperatures by means of nuclear magnetic resonance and molecular dynamics simulation. The relationship between various conformations and the observed sweetness of rebaudioside A is described.

  11. On the connection between nonmonotonic taste behavior and molecular conformation in solution: The case of rebaudioside-A

    Science.gov (United States)

    Chopade, Prashant D.; Sarma, Bipul; Santiso, Erik E.; Simpson, Jeffrey; Fry, John C.; Yurttas, Nese; Biermann, Kari L.; Chen, Jie; Trout, Bernhardt L.; Myerson, Allan S.

    2015-12-01

    The diterpene steviol glycoside, rebaudioside A, is a natural high potency non-caloric sweetener extracted from the leaves of Stevia rebaudiana. This compound shows a parabolic change in sweet taste intensity with temperature which contrasts with the general finding for other synthetic or natural sweeteners whose sweet taste increases with temperature. The nonmonotonic taste behavior was determined by sensory analysis using large taste panels. The conformational landscape of rebaudioside A was established at a range of temperatures by means of nuclear magnetic resonance and molecular dynamics simulation. The relationship between various conformations and the observed sweetness of rebaudioside A is described.

  12. Molecular detection of plant pathogenic bacteria using polymerase chain reaction single-strand conformation polymorphism

    Institute of Scientific and Technical Information of China (English)

    Chandrashekar Srinivasa; Umesha Sharanaiah; Chandan Shivamallu

    2012-01-01

    The application of polymerase chain reaction (PCR) technology to molecular diagnostics holds great promise for the early identification of agriculturally important plant pathogens.Ralstonia solanacearum,Xanthomoans axonopodis pv.vesicatoria,and Xanthomonas oryzae pv.oryzae are phytopathogenic bacteria,which can infect vegetables,cause severe yield loss.PCR-single-strand conformation polymorphism (PCR-SSCP) is a simple and powerful technique for identifying sequence changes in amplified DNA.The technique of PCR-SSCP is being exploited so far,only to detect and diagnose human bacterial pathogens in addition to plant pathogenic fungi.Selective media and serology are the commonly used methods for the detection of plant pathogens in infected plant materials.In this study,we developed PCR-SSCP technique to identify phytopathogenic bacteria.The PCR product was denatured and separated on a non-denaturing polyacrylamide gel.SSCP banding patterns were detected by silver staining of nucleic acids.We tested over 56 isolates of R. solanacearum,44 isolates of X. axonopodis pv.vesicatoria,and 20 isolates of X.oryzae pv.oryzae.With the use of universal primer 16S rRNA,we could discriminate such species at the genus and species levels.Speciesspecific patterns were obtained for bacteria R.solanacearum,X.axonopodis pv.vesicatoria,and X.oryzae pv.oryzae.The potential use of PCR-SSCP technique for the detection and diagnosis of phytobacterial pathogens is discussed in the present paper.

  13. Charge-dependent conformations and dynamics of pamam dendrimers revealed by neutron scattering and molecular dynamics

    Science.gov (United States)

    Wu, Bin

    Neutron scattering and fully atomistic molecular dynamics (MD) are employed to investigate the structural and dynamical properties of polyamidoamine (PAMAM) dendrimers with ethylenediamine (EDA) core under various charge conditions. Regarding to the conformational characteristics, we focus on scrutinizing density profile evolution of PAMAM dendrimers as the molecular charge of dendrimer increases from neutral state to highly charged condition. It should be noted that within the context of small angle neutron scattering (SANS), the dendrimers are composed of hydrocarbon component (dry part) and the penetrating water molecules. Though there have been SANS experiments that studied the charge-dependent structural change of PAMAM dendrimers, their results were limited to the collective behavior of the aforementioned two parts. This study is devoted to deepen the understanding towards the structural responsiveness of intra-molecular polymeric and hydration parts separately through advanced contrast variation SANS data analysis scheme available recently and unravel the governing principles through coupling with MD simulations. Two kinds of acids, namely hydrochloric and sulfuric acids, are utilized to tune the pH condition and hence the molecular charge. As far as the dynamical properties, we target at understanding the underlying mechanism that leads to segmental dynamic enhancement observed from quasielstic neutron scattering (QENS) experiment previously. PAMAM dendrimers have a wealth of potential applications, such as drug delivery agency, energy harvesting medium, and light emitting diodes. More importantly, it is regarded as an ideal system to test many theoretical predictions since dendrimers conjugate both colloid-like globular shape and polymer-like flexible chains. This Ph.D. research addresses two main challenges in studying PAMAM dendrimers. Even though neutron scattering is an ideal tool to study this PAMAM dendrimer solution due to its matching temporal and

  14. Conformational analysis of phloroglucinols from hypericum Brasiliense by using x-ray diffraction and molecular modeling

    Energy Technology Data Exchange (ETDEWEB)

    Leal, Katia Z.; Lindgren, Eric B.; Correa, Arthur L., E-mail: kzleal@uol.com.b [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil). Inst. de Quimica. Dept. de Fisico-Quimica; Yoneda, Julliane D. [Universidade Federal Fluminense (UFF), Volta Redonda, RJ (Brazil). Polo Universitario de Volta Redonda; Pinheiro, Carlos B. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Fisica; Franca, Hildegardo S. [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil). Faculdade de Farmacia. Dept. de Tecnologia Farmaceutica

    2010-07-01

    In this work we intend to verify the applicability of a computational methodology to predict structural features of organic compounds with biological activity. We selected three phloroglucinols and compared their calculated conformational data with their X-ray crystallographic structure. The results showed that conformations obtained by conformational analysis with the AM1 method followed by geometry optimization by using the DFT B3LYP/6-31 G(d,p) basis set are in very good agreement with X-ray data, indicating that the methodology employed here seems to be a very useful tool in order to predict the conformational preference for this class of compounds. (author)

  15. Combined experimental powder X-ray diffraction and DFT data to obtain the lowest energy molecular conformation of friedelin

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Djalma Menezes de; Mussel, Wagner da Nova; Duarte, Lucienir Pains; Silva, Gracia Divina de Fatima; Duarte, Helio Anderson; Gomes, Elionai Cassiana de Lima [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Quimica; Guimaraes, Luciana [Universidade Federal de Sao Joao Del-Rei (UFSJ), MG (Brazil). Dept. de Ciencias Naturais; Vieira Filho, Sidney A., E-mail: bibo@ef.ufop.br [Universidade Federal de Ouro Preto (UFOP), MG (Brazil). Dept. de Farmacia

    2012-07-01

    Friedelin molecular conformers were obtained by Density Functional Theory (DFT) and by ab initio structure determination from powder X-ray diffraction. Their conformers with the five rings in chair-chair-chair-boat-boat, and with all rings in chair, are energy degenerated in gas-phase according to DFT results. The powder diffraction data reveals that rings A, B and C of friedelin are in chair, and rings D and E in boat-boat, conformation. The high correlation values among powder diffraction data, DFT and reported single crystal data indicate that the use of conventional X-ray diffractometer can be applied in routine laboratory analysis in the absence of a single-crystal diffractometer. (author)

  16. Combined experimental powder X-ray diffraction and DFT data to obtain the lowest energy molecular conformation of friedelin

    Directory of Open Access Journals (Sweden)

    Djalma Menezes de Oliveira

    2012-01-01

    Full Text Available Friedelin molecular conformers were obtained by Density Functional Theory (DFT and by ab initio structure determination from powder X-ray diffraction. Their conformers with the five rings in chair-chair-chair-boat-boat, and with all rings in chair, are energy degenerated in gas-phase according to DFT results. The powder diffraction data reveals that rings A, B and C of friedelin are in chair, and rings D and E in boat-boat, conformation. The high correlation values among powder diffraction data, DFT and reported single-crystal data indicate that the use of conventional X-ray diffractometer can be applied in routine laboratory analysis in the absence of a single-crystal diffractometer.

  17. Characteristics and bioactivities of different molecular weight polysaccharides from camellia seed cake.

    Science.gov (United States)

    Xu, Zhou; Li, Xu; Feng, Shiling; Liu, Jing; Zhou, Lijun; Yuan, Ming; Ding, Chunbang

    2016-10-01

    Four polysaccharides, namely COP-1, COP-2, COP-3 and COP-4, were ultrafiltrated from crud Camellia oleifera seed cake polysaccharides (COP-c), purified, and characterized, including the determination of antioxidant and antiproliferative activities. Their molecular weights were 7.9, 36, 83 and 225kDa, respectively. All COPs showed the similar FT-IR spectrums, but significant differentials in monosaccharide components. COP-2 exhibited the highest radical scavenging abilities. COP-1 has the strongest metal chelating capabilities. Although with higher molecular weight, COP-4 showed the poorest antioxidant abilities. These results suggested appreciate molecular weight COP possessed a better antioxidant activities. Additionally, all COPs had non-significant antiproliferative abilities in HaLa and HepG2 cells.

  18. Encapsulation of bioactive whey peptides in soy lecithin-derived nanoliposomes: Influence of peptide molecular weight.

    Science.gov (United States)

    Mohan, Aishwarya; McClements, David Julian; Udenigwe, Chibuike C

    2016-12-15

    Encapsulation of peptides can be used to enhance their stability, delivery and bioavailability. This study focused on the effect of the molecular weight range of whey peptides on their encapsulation within soy lecithin-derived nanoliposomes. Peptide molecular weight did not have a major impact on encapsulation efficiency or liposome size. However, it influenced peptide distribution amongst the surface, core, and bilayer regions of the liposomes, as determined by electrical charge (ζ-potential) and FTIR analysis. The liposome ζ-potential depended on peptide molecular weight, suggesting that the peptide charged groups were in different locations relative to the liposome surfaces. FTIR analysis indicated that the least hydrophobic peptide fractions interacted more strongly with choline on the liposome surfaces. The results suggested that the peptides were unequally distributed within the liposomes, even at the same encapsulation efficiency. These findings are important for designing delivery systems for commercial production of encapsulated peptides with improved functional attributes. PMID:27451165

  19. Characteristics and bioactivities of different molecular weight polysaccharides from camellia seed cake.

    Science.gov (United States)

    Xu, Zhou; Li, Xu; Feng, Shiling; Liu, Jing; Zhou, Lijun; Yuan, Ming; Ding, Chunbang

    2016-10-01

    Four polysaccharides, namely COP-1, COP-2, COP-3 and COP-4, were ultrafiltrated from crud Camellia oleifera seed cake polysaccharides (COP-c), purified, and characterized, including the determination of antioxidant and antiproliferative activities. Their molecular weights were 7.9, 36, 83 and 225kDa, respectively. All COPs showed the similar FT-IR spectrums, but significant differentials in monosaccharide components. COP-2 exhibited the highest radical scavenging abilities. COP-1 has the strongest metal chelating capabilities. Although with higher molecular weight, COP-4 showed the poorest antioxidant abilities. These results suggested appreciate molecular weight COP possessed a better antioxidant activities. Additionally, all COPs had non-significant antiproliferative abilities in HaLa and HepG2 cells. PMID:27341780

  20. Isatin based thiosemicarbazone derivatives as potential bioactive agents: Anti-oxidant and molecular docking studies

    Science.gov (United States)

    Haribabu, J.; Subhashree, G. R.; Saranya, S.; Gomathi, K.; Karvembu, R.; Gayathri, D.

    2016-04-01

    A new series of isatin based thiosemicarbazones has been synthesized from benzylisatin and unsubstituted/substituted thiosemicarbazides (1-5). The synthesized compounds were characterized by elemental analyses, and UV-Visible, FT-IR, 1H &13C NMR and mass spectroscopic techniques. Three dimensional molecular structure of three compounds (1, 3 and 4) was determined by single crystal X-ray crystallography. Anti-oxidant activity of the thiosemicarbazone derivatives showed their excellent scavenging effect against free radicals. In addition, all the compounds showed good anti-haemolytic activity. In silico molecular docking studies were performed to screen the anti-inflammatory and anti-tuberculosis properties of thiosemicarbazone derivatives.

  1. Lysozyme-magnesium aluminum silicate microparticles: Molecular interaction, bioactivity and release studies

    DEFF Research Database (Denmark)

    Kanjanakawinkul, Watchara; Medlicott, Natalie J.; Rades, Thomas;

    2015-01-01

    The objectives of this study were to investigate the adsorption behavior of lysozyme (LSZ) onto magnesium aluminum silicate (MAS) at various pHs and to characterize the LSZ–MAS microparticles obtained from the molecular interaction between LSZ and MAS. The results showed that LSZ could be bound...

  2. Molecular modeling and conformational IgG epitope mapping on bovine β-casein

    NARCIS (Netherlands)

    Liu, Fahui; Gao, Jinyan; Li, Xin; Chen, Hongbing

    2016-01-01

    Characterizing conformational B-cell epitopes is a key step for understanding the immunological basis of allergy contributed by β-casein. There is no resolved conformational structure of β-casein in protein data bank, and most of the previous research on epitope identification of β-casein focused

  3. Molecular modeling methods in the study and design of bioactive compounds: An introduction [Métodos de Modelagem Molecular para estudo e planejamento de compostos bioativos: Uma introdução

    Directory of Open Access Journals (Sweden)

    Carlos Mauricio R. Sant´Anna

    2009-01-01

    Full Text Available This paper presents an introduction to the main methods used in molecular modeling calculations applied in the design of bioactive compounds. An introductory description of the two approaches methods predominantly used in molecular modeling studies is presented: the classical approach, which includes molecular mechanics and molecular dynamics; and the quantum mechanical approach, which includes ab initio and semi-empirical methods. We discuss how these methods can be applied to determine the molecular structure and properties from these compounds and how to make the best choice according to the problem being addressed.

  4. Speed of conformational change: comparing explicit and implicit solvent molecular dynamics simulations.

    Science.gov (United States)

    Anandakrishnan, Ramu; Drozdetski, Aleksander; Walker, Ross C; Onufriev, Alexey V

    2015-03-10

    Adequate sampling of conformation space remains challenging in atomistic simulations, especially if the solvent is treated explicitly. Implicit-solvent simulations can speed up conformational sampling significantly. We compare the speed of conformational sampling between two commonly used methods of each class: the explicit-solvent particle mesh Ewald (PME) with TIP3P water model and a popular generalized Born (GB) implicit-solvent model, as implemented in the AMBER package. We systematically investigate small (dihedral angle flips in a protein), large (nucleosome tail collapse and DNA unwrapping), and mixed (folding of a miniprotein) conformational changes, with nominal simulation times ranging from nanoseconds to microseconds depending on system size. The speedups in conformational sampling for GB relative to PME simulations, are highly system- and problem-dependent. Where the simulation temperatures for PME and GB are the same, the corresponding speedups are approximately onefold (small conformational changes), between ∼1- and ∼100-fold (large changes), and approximately sevenfold (mixed case). The effects of temperature on speedup and free-energy landscapes, which may differ substantially between the solvent models, are discussed in detail for the case of miniprotein folding. In addition to speeding up conformational sampling, due to algorithmic differences, the implicit solvent model can be computationally faster for small systems or slower for large systems, depending on the number of solute and solvent atoms. For the conformational changes considered here, the combined speedups are approximately twofold, ∼1- to 60-fold, and ∼50-fold, respectively, in the low solvent viscosity regime afforded by the implicit solvent. For all the systems studied, 1) conformational sampling speedup increases as Langevin collision frequency (effective viscosity) decreases; and 2) conformational sampling speedup is mainly due to reduction in solvent viscosity rather than

  5. Bioactive substances

    Digital Repository Service at National Institute of Oceanography (India)

    Wahidullah, S.

    Chemistry related to certain bioactive molecules, from Indian Ocean Region, developed into drugs or which served as models for the synthesis of more effective bioactive substances or in use in fundamental studies of physiological and biochemical...

  6. Conformations of Carnosine in Aqueous Solutions by All-Atom Molecular Dynamics Simulations and 2D-NOSEY Spectrum

    Institute of Scientific and Technical Information of China (English)

    Rong Zhang; Dan Wang; Wen-juan Wu

    2013-01-01

    All-atom molecular simulations and two-dimensional nuclear overhauser effect spectrum have been used to study the conformations of carnosine in aqueous solution.Intramolecular distances,root-mean-square deviation,radius of gyration,and solvent-accessible surface are used to characterize the properties of the carnosine.Carnosine can shift between extended and folded states,but exists mostly in extended state in water.Its preference for extension in pure water has been proven by the 2D nuclear magnetic resonance (NMR) experiment.The NMR experimental results are consistent with the molecular dynamics simulations.

  7. MELTING AND CRYSTALLIZATION BEHAVIOR OF AN AROMATIC POLY (AZOMETHINE ETHER) WITH NON-LINEARLY SHAPED MOLECULAR CONFORMATIONS

    Institute of Scientific and Technical Information of China (English)

    HOU Jianan; XU Mao; LI Xiaofang; ZHANG Qizhen

    1995-01-01

    The melting and crystallization behavior have been investigated for an aromatic poly (azomethine ether)with non-linearly shaped molecular conformations.This polymer was found to undergo multiple melting processes and its phase transition behavior was influenced sensitively by the thermal history of sample. A significant difference between the polymer chain aggregation abilities of samples cooled from the different states was observed. The possible molecular morphology and aggregation models for describing the structures of this polymer were proposed and discussed. The crystallization behavior of the samples cooled from the partially isotropic state and the influence of cooling rate on it have also been examined with DSC.

  8. Molecular Dynamics Simulations of the STAS Domains of Rat Prestin and Human Pendrin Reveal Conformational Motions in Conserved Flexible Regions

    Directory of Open Access Journals (Sweden)

    Alok K. Sharma

    2014-02-01

    Full Text Available Background: Molecular dynamics (MD simulations provide valuable information on the conformational changes that accompany time-dependent motions in proteins. The reported crystal structure of rat prestin (PDB 3LLO is remarkable for an α1-α2 inter-helical angle that differs substantially from those observed in bacterial STAS domains of SulP anion transporters and anti-sigma factor antagonists. However, NMR data on the rat prestin STAS domain in solution suggests dynamic features at or near the α1-α2 helical region (Pasqualetto et al JMB, 2010. We therefore performed a 100 ns 300K MD simulation study comparing the STAS domains of rat prestin and (modeled human pendrin, to explore possible conformational flexibility in the region of the α1 and α2 helices. Methods: The conformation of the loop missing in the crystal structure of rat prestin STAS (11 amino acids between helix α1 and strand β3 was built using Modeller. MD simulations were performed with GROMACSv4.6 using GROMOS96 53a6 all-atom force field. Results: A subset of secondary structured elements of the STAS domains exhibits significant conformational changes during the simulation time course. The conformationally perturbed segments include the majority of loop regions, as well as the α1 and α2 helices. A significant decrease in the α1-α2 inter-helical angle observed across the simulation trajectory leads to closer helical packing at their C-termini. The end-simulation conformations of the prestin and pendrin STAS domains, including their decreased α1-α2 inter-helical angles, resemble more closely the packing of corresponding helices in the STAS structures of bacterial SulP transporters Rv1739c and ychM, as well as those of the anti-sigma factor antagonists. Several structural segments of the modeled human pendrin STAS domain exhibit larger atomic motions and greater conformational deviations than the corresponding regions of rat prestin, predicting that the human pendrin STAS

  9. Modeling signal propagation mechanisms and ligand-based conformational dynamics of the Hsp90 molecular chaperone full-length dimer.

    Directory of Open Access Journals (Sweden)

    Giulia Morra

    2009-03-01

    Full Text Available Hsp90 is a molecular chaperone essential for protein folding and activation in normal homeostasis and stress response. ATP binding and hydrolysis facilitate Hsp90 conformational changes required for client activation. Hsp90 plays an important role in disease states, particularly in cancer, where chaperoning of the mutated and overexpressed oncoproteins is important for function. Recent studies have illuminated mechanisms related to the chaperone function. However, an atomic resolution view of Hsp90 conformational dynamics, determined by the presence of different binding partners, is critical to define communication pathways between remote residues in different domains intimately affecting the chaperone cycle. Here, we present a computational analysis of signal propagation and long-range communication pathways in Hsp90. We carried out molecular dynamics simulations of the full-length Hsp90 dimer, combined with essential dynamics, correlation analysis, and a signal propagation model. All-atom MD simulations with timescales of 70 ns have been performed for complexes with the natural substrates ATP and ADP and for the unliganded dimer. We elucidate the mechanisms of signal propagation and determine "hot spots" involved in interdomain communication pathways from the nucleotide-binding site to the C-terminal domain interface. A comprehensive computational analysis of the Hsp90 communication pathways and dynamics at atomic resolution has revealed the role of the nucleotide in effecting conformational changes, elucidating the mechanisms of signal propagation. Functionally important residues and secondary structure elements emerge as effective mediators of communication between the nucleotide-binding site and the C-terminal interface. Furthermore, we show that specific interdomain signal propagation pathways may be activated as a function of the ligand. Our results support a "conformational selection model" of the Hsp90 mechanism, whereby the protein may

  10. From Chemistry to Behavior. Molecular Structure and Bioactivity of Repellents against Ixodes ricinus Ticks.

    Directory of Open Access Journals (Sweden)

    Simone Del Fabbro

    Full Text Available Tick-borne zoonoses are considered as emerging diseases. Tick repellents represent an effective tool for reducing the risk of tick bite and pathogens transmission. Previous work demonstrated the repellent activity of the phenylpropanoid eugenol against Ixodes ricinus; here we investigate the relationship between molecular structure and repellency in a group of substances related to that compound. We report the biological activity of 18 compounds varying for the presence/number of several moieties, including hydroxyl and methoxy groups and carbon side-chain. Each compound was tested at different doses with a bioassay designed to measure repellency against individual tick nymphs. Both vapor pressure and chemical features of the tested compounds appeared to be related to repellency. In particular, the hydroxyl and methoxy groups as well as the side-chain on the benzene ring seem to play a role. These results are discussed in light of available data on chemical perception in ticks. In the course of the study new repellent compounds were identified; the biological activity of some of them (at least as effective as the "gold standard" repellent DEET appears to be very promising from a practical point of view.

  11. Bioactive compounds from culinary herbs inhibit a molecular target for type 2 diabetes management, dipeptidyl peptidase IV

    Science.gov (United States)

    Greek oregano (Origanum vulgare), marjoram (Origanum majorana), rosemary (Rosmarinus officinalis) and Mexican oregano (Lippia graveolens) are concentrated sources of bioactive compounds. The aims of this study were to characterize extracts from greenhouse grown or commercially purchased herbs for th...

  12. Role of the Subunits Interactions in the Conformational Transitions in Adult Human Hemoglobin: an Explicit Solvent Molecular Dynamics Study

    CERN Document Server

    Yusuff, Olaniyi K; Bussi, Giovanni; Raugei, Simone

    2012-01-01

    Hemoglobin exhibits allosteric structural changes upon ligand binding due to the dynamic interactions between the ligand binding sites, the amino acids residues and some other solutes present under physiological conditions. In the present study, the dynamical and quaternary structural changes occurring in two unligated (deoxy-) T structures, and two fully ligated (oxy-) R, R2 structures of adult human hemoglobin were investigated with molecular dynamics. It is shown that, in the sub-microsecond time scale, there is no marked difference in the global dynamics of the amino acids residues in both the oxy- and the deoxy- forms of the individual structures. In addition, the R, R2 are relatively stable and do not present quaternary conformational changes within the time scale of our simulations while the T structure is dynamically more flexible and exhibited the T\\rightarrow R quaternary conformational transition, which is propagated by the relative rotation of the residues at the {\\alpha}1{\\beta}2 and {\\alpha}2{\\b...

  13. Molecular Fluorescence Lifetime Fluctuations: On the Possible Role of Conformational Effects

    NARCIS (Netherlands)

    Vallée, R.A.L.; Vancso, G.J.; Hulst, van N.F.; Calbert, J.-P.; Cornil, J.; Brédas, J.L.

    2003-01-01

    The radiative lifetime of single 1,1'-dioctadecyl-3,3,3',3'- etramethylindodicarbocyanine molecules, embedded in a polymer thin film, has been characterized. At room temperature the chemically identical molecules exhibit strong fluctuations in their fluorescence lifetime. The possible conformational

  14. The effect of gauche molecular conformations on the phase diagram of a Langmuir monolayer

    NARCIS (Netherlands)

    Zangi, R; Rice, SA

    2003-01-01

    Experimental and simulation studies have shown that the gauche conformational degrees of freedom of long-chain amphiphile molecules assembled in a dense Langmuir monolayer play an important role in determining the structures of the several phases that the monolayer supports. Nevertheless, for simpli

  15. From flexibility to function: Molecular dynamics simulations of conformational changes in chaperones and photoreceptors

    NARCIS (Netherlands)

    K. Singhal

    2016-01-01

    Proteins are uniquely-shaped macromolecules that function as biological machines, and regulate a living cell’s behavior. Crucial to protein function is the folding of the polypeptide chain into a unique well-defined three-dimensional conformation. In complex cell environments, the spontaneous unassi

  16. Relationship between Oversulfation and Conformation of Low and High Molecular Weight Fucoidans and Evaluation of Their in Vitro Anticancer Activity

    Directory of Open Access Journals (Sweden)

    Myoung Lae Cho

    2010-12-01

    Full Text Available Low and high molecular weight fucoidans (F5-30K and F>30K were chemically modified through the addition of sulfate groups, and the effect of oversulfation on the in vitro anticancer activity was investigated. After the addition of sulfate groups, a considerable increase of 35.5 to 56.8% was observed in the sulfate content of the F5-30K fraction, while the sulfate content of the F>30K fraction increased to a lesser extent (from 31.7 to 41.2%. Significant differences in anticancer activity were observed between the oversulfated F5–30K and F>30K fractions, with activities of 37.3–68.0% and 20.6–35.8%, respectively. This variation in the anticancer activity of oversulfated fucoidan derivatives was likely due to differences in their sulfate content. The results suggest that the molecular conformation of these molecules is closely related to the extent of sulfation in the fucan backbones and that the sulfates are preferably substituted when the fucoidan polymers are in a loose molecular conformation.

  17. Molecular Docking Study of Conformational Polymorph: Building Block of Crystal Chemistry

    Directory of Open Access Journals (Sweden)

    Rashmi Dubey

    2013-01-01

    Full Text Available Two conformational polymorphs of novel 2-[2-(3-cyano-4,6-dimethyl-2-oxo-2H-pyridin-1-yl-ethoxy]-4,6-dimethyl nicotinonitrile have been developed. The crystal structure of both polymorphs (1a and 1b seems to be stabilized by weak interactions. A difference was observed in the packing of both polymorphs. Polymorph 1b has a better binding affinity with the cyclooxygenase (COX-2 receptor than the standard (Nimesulide.

  18. Molecular Docking Study of Conformational Polymorph: Building Block of Crystal Chemistry

    Science.gov (United States)

    Dubey, Rashmi; Tewari, Ashish Kumar; Singh, Ved Prakash; Singh, Praveen; Dangi, Jawahar Singh; Puerta, Carmen; Valerga, Pedro; Kant, Rajni

    2013-01-01

    Two conformational polymorphs of novel 2-[2-(3-cyano-4,6-dimethyl-2-oxo-2H-pyridin-1-yl)-ethoxy]-4,6-dimethyl nicotinonitrile have been developed. The crystal structure of both polymorphs (1a and 1b) seems to be stabilized by weak interactions. A difference was observed in the packing of both polymorphs. Polymorph 1b has a better binding affinity with the cyclooxygenase (COX-2) receptor than the standard (Nimesulide). PMID:24250264

  19. Conformational Dynamics in FKBP Domains: Relevance to Molecular Signaling and Drug Design.

    Science.gov (United States)

    LeMaster, David M; Hernandez, Griselda

    2015-01-01

    Among the 22 FKBP domains in the human genome, FKBP12.6 and the first FKBP domains (FK1) of FKBP51 and FKBP52 are evolutionarily and structurally most similar to the archetypical FKBP12. As such, the development of inhibitors with selectivity among these four FKBP domains poses a significant challenge for structure-based design. The pleiotropic effects of these FKBP domains in a range of signaling processes such as the regulation of ryanodine receptor calcium channels by FKBP12 and FKBP12.6 and steroid receptor regulation by the FK1 domains of FKBP51 and FKBP52 amply justify the efforts to develop selective therapies. In contrast to their close structural similarities, these four FKBP domains exhibit a substantial diversity in their conformational flexibility. A number of distinct conformational transitions have been characterized for FKBP12 spanning timeframes from 20 s to 10 ns and in each case these dynamics have been shown to markedly differ from the conformational behavior for one or more of the other three FKBP domains. Protein flexibilitybased inhibitor design could draw upon the transitions that are significantly populated in only one of the targeted proteins. Both the similarities and differences among these four proteins valuably inform the understanding of how dynamical effects propagate across the FKBP domains as well as potentially how such intramolecular transitions might couple to the larger scale transitions that are central to the signaling complexes in which these FKBP domains function.

  20. Molecular and environmental factors governing non-covalent bonding interactions and conformations of phosphorous functionalized γ-cyclodextrin hydrate systems.

    Science.gov (United States)

    Ivanova, Bojidarka; Spiteller, Michael

    2016-06-01

    Recent strategies in molecular drugs-design shift efforts to nanomedicine. Large supra-molecular inclusion systems are implemented as therapeutics. The sophistication of design is based on major advances of cyclodextrins (CDs) as host molecules. They are friendly towards biological environment. CDs have good (bio)compatibility as well. CDs can form host-guest macromolecular systems incorporating small molecules with suitable shapes due to non-covalent interactions. Innovative strategies yield to polymeric nano-particles; micelles; linear polymers and/or CDs-functionalized dendrimeric nanostructures; nanofibers as well as hydrogels. Attractive are phosphorous containing (bio)matrerials, having high selectivity toward biological active molecules. The non-covalent interactions in aquatic CD-systems contribute to stability of host-guest systems under physiological conditions, determining conformational preferences of host-CD macromolecule and guest small molecular template. In this paper we have reported complementation application of mass spectrometric (MS) and quantum chemical analysis of phosphorous chemically substituted γ-cyclodextrin hydrates γ-CDPO/nH2O (n ∊ [0-14]), studying neutral and polynegatively charged molecules as an effort to describe realistic a representative scale of physiological conditions. The binding affinity and molecular conformations are discussed. The 250 neutral and charged systems (γ-CDPOHm/nH2O, n ∊ [10][0,14], m ∊ [0,15], γ-CDPOH-8/nH2O.8Na(+), and γ-CDPOH-16/nH2O.16Na(+)) in four main domains of non-covalent hydrogen bonding interactions are studied. PMID:26944657

  1. Molecular dynamics simulation of phosphorylation-induced conformational transitions in the mycobacterium tuberculosis response regulator PrrA

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Guo [Los Alamos National Laboratory; Mcmahon, Benjamin H [Los Alamos National Laboratory; Tung, Chang - Shung [Los Alamos National Laboratory

    2008-01-01

    Phosphorylation-activated modulation of response regulators (RR) is predominantly used by bacteria as a strategy in regulating their two-component signaling (TCS) systems, the underlying molecular mechanisms are however far from fully understood. In this work we have conducted a molecular dynamics (MD) simulation of the phosphorylation-induced conformational transitions of RRs with the Mycobacterium Tuberculosis PrrA as a particular example. Starting from the full-length inactive structure of PrrA we introduced a local disturbance by phosphorylating the conserved aspartic acid residue, Asp-58, in the regulatory domain. A Go-model-type algorithm packaged with AMBER force fields was then applied to simulate the dynamics upon phosphorylation. The MD simulation shows that the phosphorylation of Asp-58 facilitates PrrA, whose inactive state has a compact conformation with a closed interdomain interface, to open up with its interdomain separation being increased by an average of about 1.5 {angstrom} for a simulation of 20 ns. The trans-activation loop, which is completely buried within the interdomain interface in the inactive PrrA, is found to become more exposed with the phosphorylated structure as well. These results provide more structural details of how the phosphorylation of a local aspartate activates PrrA to undergo a global conformational rearrangement toward its extended active state. This work also indicates that MD simulations can serve as a fast tool to unravel the regulation mechanisms of all RRs, which is especially valuable when the structures of full-length active RRs are currently unavailable.

  2. Conformational transitions of single polymer adsorption in poor solvent: Wetting transition due to molecular confinement induced line tension

    Science.gov (United States)

    Wei, Hsien-Hung; Li, Yen-Ching

    2016-07-01

    We report a theory capable of describing conformational transitions for single polymer adsorption in a poor solvent. We show that an additional molecular confinement effect near the contact line can act exactly like line tension, playing a critical role in the behavior of an absorbed polymer chain. Using this theory, distinct conformational states: desorbed globule (DG), surface attached cap (SAC), and adsorbed lens (AL), can be vividly revealed, resembling the drying-wetting transition of a nanodroplet. But the transitions between these states can behave rather differently from those in the usual wetting transitions. The DG-SAC transition is discrete, occurring at the adsorption threshold when the globule size at the desorbed state is equal to the adsorption blob. The SAC-AL transition is smooth for finite chain lengths, but can change to discontinuous in the infinite chain limit, characterized by the different end-to-end exponent 3/8 and the unique crossover exponent 1/4. Distinctive critical exponents near this transition are also determined, indicating that it is an additional universality class of phase transitions. This work also sheds light on nanodrop spreading, wherein the important role played by line tension might simply be a manifestation of the local molecular confinement near the contact line.

  3. The effect of poly(trimethylene carbonate) molecular weight on macrophage behavior and enzyme adsorption and conformation.

    Science.gov (United States)

    Vyner, Moira C; Li, Anne; Amsden, Brian G

    2014-11-01

    Poly(trimethylene carbonate) (PTMC) with molecular weights greater than 100 kg/mol is known to degrade readily in vivo while PTMC of less than 70 kg/mol is resistant to degradation. The reason for the molecular weight dependent degradation rate of PTMC is unclear, and may be due to differences in macrophage behavior or enzyme adsorption or activity. Macrophage number and production of reactive oxygen species (ROS) and esterase were measured when cultured on 60 and 100 kg/mol PTMC. Cholesterol esterase and lipase were adsorbed to 60 and 100 kg/mol PTMC and mass and viscoelastic properties of the adsorbed enzyme layers were measured. No significant differences were observed in macrophage number or production of degradative species. Significant differences were measured in mass, shear modulus and viscosity of the adsorbed cholesterol esterase layer, suggesting that the cholesterol esterase is adsorbing in a different conformation on the 60 and 100 kg/mol PTMC. Despite similar bulk moduli, the surface modulus of 60 kg/mol PTMC was significantly lower than 100 kg/mol. It is proposed that the difference in surface stiffness and polymer chain flexibility affect the arrangement of water bound to and freed from the polymer chains during adsorption, thus affecting enzymatic adsorption, conformation, and activity. PMID:25109440

  4. Identification of a Novel Parallel beta-Strand Conformation within Molecular Monolayer of Amyloid Peptide

    DEFF Research Database (Denmark)

    Liu, Lei; Li, Qiang; Zhang, Shuai;

    2016-01-01

    technique with force controlled in pico-Newton range, combining with molecular dynamic simulation. The identified parallel beta-strand-like structure of molecular monolayer is distinct from the antiparallel beta-strand structure of A beta(33-42) amyloid fibril. This finding enriches the molecular structures....... In this work, the early A beta(33-42) aggregates forming the molecular monolayer at hydrophobic interface are investigated. The molecular monolayer of amyloid peptide A beta(33-42) consisting of novel parallel beta-strand-like structure is further revealed by means of a quantitative nanomechanical spectroscopy......The differentiation of protein properties and biological functions arises from the variation in the primary and secondary structure. Specifically, in abnormal assemblies of protein, such as amyloid peptide, the secondary structure is closely correlated with the stable ensemble and the cytotoxicity...

  5. Quantum/molecular mechanics study of firefly bioluminescence on luciferase oxidative conformation

    Science.gov (United States)

    Pinto da Silva, Luís; Esteves da Silva, Joaquim C. G.

    2014-07-01

    This is the first report of a computational study of the color tuning mechanism of firefly bioluminescence, using the oxidative conformation of luciferase. The results of these calculations demonstrated that the electrostatic field generated by luciferase is fundamental both for the emission shift and efficiency. Further calculations indicated that a shift in emission is achieved by modulating the energy, at different degrees, of the emissive and ground states. These differences in energy modulation will then lead to changes in the energy gap between the states.

  6. Steered molecular dynamics simulations of a type IV pilus probe initial stages of a force-induced conformational transition.

    Directory of Open Access Journals (Sweden)

    Joseph L Baker

    2013-04-01

    Full Text Available Type IV pili are long, protein filaments built from a repeating subunit that protrudes from the surface of a wide variety of infectious bacteria. They are implicated in a vast array of functions, ranging from bacterial motility to microcolony formation to infection. One of the most well-studied type IV filaments is the gonococcal type IV pilus (GC-T4P from Neisseria gonorrhoeae, the causative agent of gonorrhea. Cryo-electron microscopy has been used to construct a model of this filament, offering insights into the structure of type IV pili. In addition, experiments have demonstrated that GC-T4P can withstand very large tension forces, and transition to a force-induced conformation. However, the details of force-generation, and the atomic-level characteristics of the force-induced conformation, are unknown. Here, steered molecular dynamics (SMD simulation was used to exert a force in silico on an 18 subunit segment of GC-T4P to address questions regarding the nature of the interactions that lead to the extraordinary strength of bacterial pili. SMD simulations revealed that the buried pilin α1 domains maintain hydrophobic contacts with one another within the core of the filament, leading to GC-T4P's structural stability. At the filament surface, gaps between pilin globular head domains in both the native and pulled states provide water accessible routes between the external environment and the interior of the filament, allowing water to access the pilin α1 domains as reported for VC-T4P in deuterium exchange experiments. Results were also compared to the experimentally observed force-induced conformation. In particular, an exposed amino acid sequence in the experimentally stretched filament was also found to become exposed during the SMD simulations, suggesting that initial stages of the force induced transition are well captured. Furthermore, a second sequence was shown to be initially hidden in the native filament and became exposed upon

  7. Molecular architecture with carbohydrate functionalized β-peptides adopting 314-helical conformation

    Directory of Open Access Journals (Sweden)

    Nitin J. Pawar

    2014-04-01

    Full Text Available Carbohydrate recognition is essential in cellular interactions and biological processes. It is characterized by structural diversity, multivalency and cooperative effects. To evaluate carbohydrate interaction and recognition, the structurally defined attachment of sugar units to a rigid template is highly desired. β-Peptide helices offer conformationally stable templates for the linear presentation of sugar units in defined distances. The synthesis and β-peptide incorporation of sugar-β-amino acids are described providing the saccharide units as amino acid side chain. The respective sugar-β-amino acids are accessible by Michael addition of ammonia to sugar units derivatized as α,β-unsaturated esters. Three sugar units were incorporated in β-peptide oligomers varying the sugar (glucose, galactose, xylose and sugar protecting groups. The influence of sugar units and the configuration of sugar-β-amino acids on β-peptide secondary structure were investigated by CD spectroscopy.

  8. Raman spectroscopy study of rotational isomerism and molecular conformation of ethyl through hexadecyl acetates

    Science.gov (United States)

    Mido, Yoshiyuki; Shono, Tomofumi; Matsuura, Hiroatsu

    1991-06-01

    Raman spectra of ethyl through hexadecyl acetates have been recorded in the liquid and crystalline states. The spectra were analysed on the basis of the relations between the observed wavenumbers and the number of alkyl carbon atoms, comparisons of the wavenumbers of the accordion vibrations between the acetates and n-alkanes, and normal coordinate treatment. The results indicate that the acetate molecules in crystals, except for butyl and pentyl acetates, are in the alltrans conformation with the acetoxy-group part incorporated and that the molecules of butyl and pentyl homologues are in the TTGT and TTGTT forms (T, trans; G, gauche), respectively. The spectral analyses suggest that the crystal structure of several acetates is orthorhombic.

  9. Variety of molecular conformation of plasmid pUC18 DNA and solenoidally supercoiled DNA

    Institute of Scientific and Technical Information of China (English)

    黄熙泰; 王照清; 吴永文; 樊廷玉; 王树荣; 王勖焜

    1996-01-01

    The plasmid pUC18 DNA isolated from Escherichia coli HB101 were analyzed by two-dimensional agarose gel electrophoresis and hybridization. The results show that the DNA sample can be separated into six groups of different structural components. The plectonemically and solenoidally supercoiled pUC18 DNA coexist in it. These two different conformations of supercoiled DNA are interchangeable with the circumstances (ionic strength and type, etc.). The amount of solenoidally supercoiled pUC18 DNA in the samples can be changed by treatment of DNA topoisome rases. Under an electron microscope, the solenoidal supercoiling DNA has a round shape with an average diameter of 45 nm. The facts suggest that solenoidaUy supercoiled DNA be a structural entity independent of histones. The polymorphism of DNA structure may be important to packing of DNA in vivo.

  10. Optimized Solid Phase-Assisted Synthesis of Dendrons Applicable as Scaffolds for Radiolabeled Bioactive Multivalent Compounds Intended for Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Gabriel Fischer

    2014-05-01

    Full Text Available Dendritic structures, being highly homogeneous and symmetric, represent ideal scaffolds for the multimerization of bioactive molecules and thus enable the synthesis of compounds of high valency which are e.g., applicable in radiolabeled form as multivalent radiotracers for in vivo imaging. As the commonly applied solution phase synthesis of dendritic scaffolds is cumbersome and time-consuming, a synthesis strategy was developed that allows for the efficient assembly of acid amide bond-based highly modular dendrons on solid support via standard Fmoc solid phase peptide synthesis protocols. The obtained dendritic structures comprised up to 16 maleimide functionalities and were derivatized on solid support with the chelating agent DOTA. The functionalized dendrons furthermore could be efficiently reacted with structurally variable model thiol-bearing bioactive molecules via click chemistry and finally radiolabeled with 68Ga. Thus, this solid phase-assisted dendron synthesis approach enables the fast and straightforward assembly of bioactive multivalent constructs for example applicable as radiotracers for in vivo imaging with Positron Emission Tomography (PET.

  11. Effect of graphene oxide on the conformational transitions of amyloid beta peptide: A molecular dynamics simulation study.

    Science.gov (United States)

    Baweja, Lokesh; Balamurugan, Kanagasabai; Subramanian, Venkatesan; Dhawan, Alok

    2015-09-01

    The interactions between nanomaterials (NMs) and amyloid proteins are central to the nanotechnology-based diagnostics and therapy in neurodegenerative disorders such as Alzheimer's and Parkinson's. Graphene oxide (GO) and its derivatives have shown to modulate the aggregation pattern of disease causing amyloid beta (Aβ) peptide. However, the mechanism is still not well understood. Using molecular dynamics simulations, the effect of graphene oxide (GO) and reduced graphene oxide (rGO) having carbon:oxygen ratio of 4:1 and 10:1, respectively, on the conformational transitions (alpha-helix to beta-sheet) and the dynamics of the peptide was investigated. GO and rGO decreased the beta-strand propensity of amino acid residues in Aβ. The peptide displayed different modes of adsorption on GO and rGO. The adsorption on GO was dominated by electrostatic interactions, whereas on rGO, both van der Waals and electrostatic interactions contributed in the adsorption of the peptide. Our study revealed that the slight increase in the hydrophobic patches on rGO made it more effective inhibitor of conformational transitions in the peptide. Alpha helix-beta sheet transition in Aβ peptide could be one of the plausible mechanism by which graphene oxide may inhibit amyloid fibrillation.

  12. Low molecular weight oligomers of amyloid peptides display β-barrel conformations: A replica exchange molecular dynamics study in explicit solvent

    Science.gov (United States)

    De Simone, Alfonso; Derreumaux, Philippe

    2010-04-01

    The self-assembly of proteins and peptides into amyloid fibrils is connected to over 40 pathological conditions including neurodegenerative diseases and systemic amyloidosis. Diffusible, low molecular weight protein and peptide oligomers that form in the early steps of aggregation appear to be the harmful cytotoxic species in the molecular etiology of these diseases. So far, the structural characterization of these oligomers has remained elusive owing to their transient and dynamic features. We here address, by means of full atomistic replica exchange molecular dynamics simulations, the energy landscape of heptamers of the amyloidogenic peptide NHVTLSQ from the beta-2 microglobulin protein. The simulations totaling 5 μs show that low molecular weight oligomers in explicit solvent consist of β-barrels in equilibrium with amorphous states and fibril-like assemblies. The results, also accounting for the influence of the pH on the conformational properties, provide a strong evidence of the formation of transient β-barrel assemblies in the early aggregation steps of amyloid-forming systems. Our findings are discussed in terms of oligomers cytotoxicity.

  13. Molecular conformational analysis, vibrational spectra, NBO, NLO analysis and molecular docking study of bis[(E)-anthranyl-9-acrylic]anhydride based on density functional theory calculations.

    Science.gov (United States)

    Mary, Y Sheena; Panicker, C Yohannan; Thiemann, Thies; Al-Azani, Mariam; Al-Saadi, Abdulaziz A; Van Alsenoy, C; Raju, K; War, Javeed Ahmad; Srivastava, S K

    2015-01-01

    FT-IR and FT-Raman spectra of bis[(E)-anthranyl-9-acrylic]anhydride were recorded and analyzed. The conformational behavior is also investigated. The vibrational wave numbers were calculated using density functional theory (DFT) quantum chemical calculations. The data obtained from wave number calculations are used to assign vibrational bands obtained in Infrared and Raman spectra. Potential energy distribution was done using GAR2PED program. The geometrical parameters are compared with related structures. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using Natural Bonding Orbital (NBO) analysis. The Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) analysis are used to determine the charge transfer within the molecule. Molecular Electrostatic Potential (MEP) was performed by the DFT method. The calculated first hyperpolarizability of the title compound is comparable with the reported values of similar derivatives and is 4.23 times that of the standard nonlinear optical (NLO) material urea and the title compound and its derivatives are an attractive object for future studies of nonlinear optical properties. To evaluate the in silico antitumor activity of the title compound molecular docking studies were carried out against protein Bcl-xL. The (1)H-NMR spectrum is also reported. PMID:26143327

  14. Chemical structure-optical property understanding in bisphenyls and substituted polycarbonates by molecular simulations: Role of polarizabilities and conformations

    Science.gov (United States)

    Natarajan, Upendra; Sulatha, M. S.

    2005-03-01

    We present calculations of polarizability tensors, optical anisotropy of organic molecules, repeating units and polymer chains of several bisphenyls, bisphenol carbonates and polycarbonates with a variety of chemical substitutions.^1,2 Theoretical calculations of polarizabilities and optical birefringence of several newer structures having specific side-group substitutions which render low birefringence, not previously reported, is also shown here. Our method combines VOSRIS scheme^3, molecular geometry and conformations from force-field simulations and accurate anisotropic polarizability tensors. Aliphatic, aliphatic aromatic and cycloaliphatic substitutions reduce optical anisotropy in relation to bisphenol A polycarbonate. Calculated /x of these structurally modified polycarbonates^2 follows linear behavior with respect to experimentally observed melt stress-optical coefficient (Cm). *J. Phys. Chem. A, 107, 97 (2003) *Macromolecules, 36, 2944 (2003) *P.J. Flory, Statistical Mechanics of Chain Molecules, Wiley Interscience, New York (1969)

  15. Structural analysis of prolyl oligopeptidases using molecular docking and dynamics: insights into conformational changes and ligand binding.

    Directory of Open Access Journals (Sweden)

    Swati Kaushik

    Full Text Available Prolyl oligopeptidase (POP is considered as an important pharmaceutical target for the treatment of numerous diseases. Despite enormous studies on various aspects of POPs structure and function still some of the questions are intriguing like conformational dynamics of the protein and interplay between ligand entry/egress. Here, we have used molecular modeling and docking based approaches to unravel questions like differences in ligand binding affinities in three POP species (porcine, human and A. thaliana. Despite high sequence and structural similarity, they possess different affinities for the ligands. Interestingly, human POP was found to be more specific, selective and incapable of binding to a few planar ligands which showed extrapolation of porcine POP in human context is more complicated. Possible routes for substrate entry and product egress were also investigated by detailed analyses of molecular dynamics (MD simulations for the three proteins. Trajectory analysis of bound and unbound forms of three species showed differences in conformational dynamics, especially variations in β-propeller pore size, which was found to be hidden by five lysine residues present on blades one and seven. During simulation, β-propeller pore size was increased by ∼2 Å in porcine ligand-bound form which might act as a passage for smaller product movement as free energy barrier was reduced, while there were no significant changes in human and A. thaliana POPs. We also suggest that these differences in pore size could lead to fundamental differences in mode of product egress among three species. This analysis also showed some functionally important residues which can be used further for in vitro mutagenesis and inhibitor design. This study can help us in better understanding of the etiology of POPs in several neurodegenerative diseases.

  16. Using attenuated total reflection Fourier transform infrared spectroscopy (ATR FT-IR) to study the molecular conformation of parchment artifacts in different macroscopic states.

    Science.gov (United States)

    Gonzalez, Lee; Wade, Matthew; Bell, Nancy; Thomas, Kate; Wess, Tim

    2013-02-01

    Maintaining appropriate temperatures and relative humidity is considered essential to extending the useful life of parchment artifacts. Although the relationship between environmental factors and changes to the physical state of artifacts is reasonably understood, an improved understanding of the relationship between the molecular conformation and changes to the macroscopic condition of parchment is needed to optimize environmental conditions. Using Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR FT-IR) analysis, the conformation of the molecular structure in selected parchment samples with specific macroscopic conditions, typically discoloration and planar deformations (e.g., cockling and tearing), have been made. The results of this investigation showed that the Fourier transform infrared signal differs for parchment samples exhibiting different macroscopic conditions. In areas exhibiting planar deformation, a change in the Fourier Transform Infrared signal was observed that indicates unfolding of the molecular conformation. In comparison, the discolored samples showed a change in molecular conformation that indicates a chemical change within the collagen molecular structure. This paper discusses the possible causal associations and implications of these findings for the conservation and preservation of parchment artifacts.

  17. Co-conformational Exchange Triggered by Molecular Recognition in a Di(acylamino)pyridine-Based Molecular Shuttle Containing Two Pyridine Rings at the Macrocycle.

    Science.gov (United States)

    Martinez-Cuezva, Alberto; Carro-Guillen, Fernando; Pastor, Aurelia; Marin-Luna, Marta; Orenes, Raul-Angel; Alajarin, Mateo; Berna, Jose

    2016-06-17

    We describe the incorporation of endo-pyridine units into the tetralactam ring of di(acylamino)pyridine-based rotaxanes. This macrocycle strongly associates with the linear interlocked component as confirmed by X-ray diffraction studies of rotaxane 2 b. Dynamic NMR studies of 2 b in solution revealed a rotational energy barrier that was higher than that of the related rotaxane 2 a, which lacks of pyridine rings in the macrocycle. The macrocycle distribution of the molecular shuttle 4 b, containing two endo-pyridine rings, shows that the major co-conformer is that with the cyclic component sitting over the di(acylamino)pyridine station. DFT calculations also support the marked preference of the ring for occupying the heterocyclic binding site. The association of N-hexylthymine with the di(acylamino)pyridine binding site of 4 b led to the formation of a rare 'S'-shaped co-conformer in which the tetralactam ring interacts simultaneously with both stations of the thread. PMID:26698891

  18. The role of conformational selection in the molecular recognition of the wild type and mutants XPA67-80 peptides by ERCC1.

    Science.gov (United States)

    Fadda, Elisa

    2015-07-01

    Molecular recognition is a fundamental step in the coordination of biomolecular pathways. Understanding how recognition and binding occur between highly flexible protein domains is a complex task. The conformational selection theory provides an elegant rationalization of the recognition mechanism, especially valid in cases when unstructured protein regions are involved. The recognition of a poorly structured peptide, namely XPA67-80 , by its target receptor ERCC1, falls in this challenging study category. The microsecond molecular dynamics (MD) simulations, discussed in this work, show that the conformational propensity of the wild type XPA67-80 peptide in solution supports conformational selection as the key mechanism driving its molecular recognition by ERCC1. Moreover, all the mutations of the XPA67-80 peptide studied here cause a significant increase of its conformational disorder, relative to the wild type. Comparison to experimental data suggests that the loss of the recognized structural motifs at the microscopic time scale can contribute to the critical decrease in binding observed for one of the mutants, further substantiating the key role of conformational selection in recognition. Ultimately, because of the high sequence identity and analogy in binding, it is conceivable that the conclusions of this study on the XPA67-80 peptide also apply to the ERCC1-binding domain of the XPA protein. PMID:25973722

  19. An in silico study of the molecular basis of B-RAF activation and conformational stability

    DEFF Research Database (Denmark)

    Fratev, Filip Filipov; Jonsdottir, Svava Osk

    2009-01-01

    B-RAF kinase plays an important role both in tumour induction and maintenance in several cancers and it is an attractive new drug target. However, the structural basis of the B-RAF activation is still not well understood. RESULTS: In this study we suggest a novel molecular basis of B-RAF activation...... the A-loop and the alphaC-helix in the activating mutants, which presumably contribute to the flipping of the activation segment to an active form. Conversely, in the B-RAFD594V mutant that has impaired kinase activity, and in B-RAFWT these interactions were strong and stabilized the kinase inactive...

  20. Spectroscopy of the conformational disorder in molecular films: Tetracosane and squalane on Pt(111)

    Science.gov (United States)

    Fuhrmann, D.; Graham, A. P.

    2004-02-01

    The spectroscopic investigation of the molecular vibrations of adsorbed branched and unbranched alkane molecules using helium atom scattering (HAS) provides evidence for the thermal formation of gauche defects in tetracosane (C24H50) monolayers above 200 K. HAS results for the vibration of tetracosane molecules perpendicular to the Pt(111) surface reveal a strong frequency decrease and peak broadening above the transition temperature which can be related to a reduction of the force holding the molecules to the surface. This reduction of the force is interpreted as being due to the thermal formation of gauche defects within the tetracosane molecules.

  1. Viscoelasticity Enhancement of Surfactant Solutions Depends on Molecular Conformation: Influence of Surfactant Headgroup Structure and Its Counterion.

    Science.gov (United States)

    Lutz-Bueno, Viviane; Pasquino, Rossana; Liebi, Marianne; Kohlbrecher, Joachim; Fischer, Peter

    2016-05-01

    During the anisotropic growth from globular to wormlike micelles, the basic interactions among distinct parts of the surfactant monomer, its counterion, and additives are fundamental to tune molecular self-assembly. We investigate the addition of sodium salicylate (NaSal) to hexadecyltrimethylammonium chloride and bromide (CTAC and CTAB), 1-hexadecylpyridinium chloride and bromide (CPyCl and CPyBr), and benzyldimethylhexadecylammonium chloride (BDMC), which have the same hydrophobic tail. Their potential to enhance viscoelasticity by anisotropic micellar growth upon salt addition was compared in terms of (i) the influence of the headgroup structure, and (ii) the influence of surfactant counterion type. Employing proton nuclear magnetic resonance ((1)H NMR), we focused on the molecular conformation of surfactant monomers in the core and polar shell regions of the micelles and their interactions with increasing concentration of NaSal. The viscoelastic response was investigated by rotational and oscillatory rheology. We show that micellar growth rates can be tuned by varying the flexibility and size of the surfactant headgroup as well as the dissociation degree of the surfactant counterion, which directly influences the strength of headgroup-counterion pairing. As a consequence, the morphological transitions depend directly on charge neutralization by electrostatic screening. For example, the amount of salt necessary to start the rodlike-to-wormlike micelle growth depends directly on the number of dissociated counterions in the polar shell. PMID:27081871

  2. Assignment of Side-Chain Conformation Using Adiabatic Energy Mapping, Free Energy Perturbation, and Molecular Dynamic Simulations

    DEFF Research Database (Denmark)

    Frimurer, Thomas M.; Günther, Peter H.; Sørensen, Morten Dahl;

    1999-01-01

    adiabatic mapping, conformational change, essentialdynamics, free energy simulations, Kunitz type inhibitor *ga3(VI)......adiabatic mapping, conformational change, essentialdynamics, free energy simulations, Kunitz type inhibitor *ga3(VI)...

  3. [Which molecular biology techniques must conform to the armamentarium for basic research in uro-oncology?].

    Science.gov (United States)

    Oriola, Josep

    2013-06-01

    Molecular biology has been one of the scientific disciplines in which there has been more advances in the last years. The first impulse in the study of genetic alterations came from the discovery of DNA structure, followed by elucidation of the genetic code, the discovery of restriction enzymes and subsequently the invention of PCR, not forgetting the exponential development of computer science. All of them have allowed us to know much more about our genome and its regulation than we could imagine. The impulse in proteomics has been especially in tune up of soft methods of ionization coupled with mass spectrometry. Nevertheless, this seems to be only the beginning since today there are continuous methodological advances that will increase more, without doubt, the knowledge and applications in this discipline. PMID:23793758

  4. Nuclear magnetic resonance studies of conformations and molecular interactions in lyotropic mesophases - Applications to solubilization problems

    International Nuclear Information System (INIS)

    After having determined the structural properties of smectic liquid crystals made from double chain surfactants/water binary systems, residual anisotropic interactions and relaxation times measurements were used to investigate the molecular ordering. Phosphorus, deuterium and nitrogen NMR of the surfactant molecules evidenced their high degree of order and the strong anisotropy of their motions. Quantitative results depended on the surfactant polar head -phosphate or ammonium-, while they displayed little variations with the hydrocarbon tail size. The marked dependence of the order and dynamics of small solutes in a lamellar phase on their hydrophilic or hydrophobic behaviour was shown using the same methods. By means of para-magnetically induced relaxation, it was proved that the non-polar solute benzene is located in the organic domain of the liquid crystalline matrix. (author)

  5. Conformational and Molecular Structures of α,β-Unsaturated Acrylonitrile Derivatives: Photophysical Properties and Their Frontier Orbitals

    Directory of Open Access Journals (Sweden)

    María Judith Percino

    2016-03-01

    Full Text Available We report single crystal X-ray diffraction (hereafter, SCXRD analyses of derivatives featuring the electron-donor N-ethylcarbazole or the (4-diphenylaminophenyl moieties associated with a -CN group attached to a double bond. The compounds are (2Z-3-(4-(diphenylamino-phenyl-2-(pyridin-3-ylprop-2-enenitrile (I, (2Z-3-(4-(diphenylaminophenyl-2-(pyridin-4-yl-prop-2-enenitrile (II and (2Z-3-(9-ethyl-9H-carbazol-3-yl-2-(pyridin-2-ylenenitrile (III. SCXRD analyses reveal that I and III crystallize in the monoclinic space groups P2/c with Z’ = 2 and C2/c with Z’ = 1, respectively. Compound II crystallized in the orthorhombic space group Pbcn with Z’ = 1. The molecular packing analysis was conducted to examine the pyridine core effect, depending on the ortho, meta- and para-positions of the nitrogen atom, with respect to the optical properties and number of independent molecules (Z’. It is found that the double bond bearing a diphenylamino moiety introduced properties to exhibit a strong π-π-interaction in the solid state. The compounds were examined to evaluate the effects of solvent polarity, the role of the molecular structure, and the molecular interactions on their self-assembly behaviors. Compound I crystallized with a cell with two conformers, anti and syn, due to interaction with solvent. DFT calculations indicated the anti and syn structures of I are energetically stable (less than 1 eV. Also electrochemical and photophysical properties of the compounds were investigated, as well as the determination of optimization calculations in gas and different solvent (chloroform, cyclohexane, methanol, ethanol, tetrahydrofuran, dichloromethane and dimethyl sulfoxide in the Gaussian09 program. The effect of solvent by PCM method was also investigated. The frontier HOMO and LUMO energies and gap energies are reported.

  6. Conformational sampling enhancement of replica exchange molecular dynamics simulations using swarm particle intelligence

    International Nuclear Information System (INIS)

    In this paper, we present a new method based on swarm particle social intelligence for use in replica exchange molecular dynamics simulations. In this method, the replicas (representing the different system configurations) are allowed communicating with each other through the individual and social knowledge, in additional to considering them as a collection of real particles interacting through the Newtonian forces. The new method is based on the modification of the equations of motion in such way that the replicas are driven towards the global energy minimum. The method was tested for the Lennard-Jones clusters of N = 4,  5, and 6 atoms. Our results showed that the new method is more efficient than the conventional replica exchange method under the same practical conditions. In particular, the new method performed better on optimizing the distribution of the replicas among the thermostats with time and, in addition, ergodic convergence is observed to be faster. We also introduce a weighted histogram analysis method allowing analyzing the data from simulations by combining data from all of the replicas and rigorously removing the inserted bias

  7. Conformational sampling enhancement of replica exchange molecular dynamics simulations using swarm particle intelligence

    Science.gov (United States)

    Kamberaj, Hiqmet

    2015-09-01

    In this paper, we present a new method based on swarm particle social intelligence for use in replica exchange molecular dynamics simulations. In this method, the replicas (representing the different system configurations) are allowed communicating with each other through the individual and social knowledge, in additional to considering them as a collection of real particles interacting through the Newtonian forces. The new method is based on the modification of the equations of motion in such way that the replicas are driven towards the global energy minimum. The method was tested for the Lennard-Jones clusters of N = 4, 5, and 6 atoms. Our results showed that the new method is more efficient than the conventional replica exchange method under the same practical conditions. In particular, the new method performed better on optimizing the distribution of the replicas among the thermostats with time and, in addition, ergodic convergence is observed to be faster. We also introduce a weighted histogram analysis method allowing analyzing the data from simulations by combining data from all of the replicas and rigorously removing the inserted bias.

  8. Hamming distance geometry of a protein conformational space. Application to the clustering of a 4 ns molecular dynamics trajectory of the HIV-1 integrase catalytic core

    CERN Document Server

    Laboulais, C; Le Bret, M; Gabarro-Arpa, J; Laboulais, Cyril; Ouali, Mohammed; Bret, Marc Le; Gabarro-Arpa, Jacques

    2001-01-01

    Protein structures can be encoded into binary sequences, these are used to define a Hamming distance in conformational space: the distance between two different molecular conformations is the number of different bits in their sequences. Each bit in the sequence arises from a partition of conformational space in two halves. Thus, the information encoded in the binary sequences is also used to characterize the regions of conformational space visited by the system. We apply this distance and their associated geometric structures, to the clustering and analysis of conformations sampled during a 4 ns molecular dynamics simulation of the HIV-1 integrase catalytic core. The cluster analysis of the simulation shows a division of the trajectory into two segments of 2.6 and 1.4 ns length, which are qualitatively different: the data points to the fact that equilibration is only reached at the end of the first segment. Some length of the paper is devoted to compare the Hamming distance to the r.m.s. deviation measure. Th...

  9. Hydrocarbons depending on the chain length and head group adopt different conformations within a water-soluble nanocapsule: 1H NMR and molecular dynamics studies.

    Science.gov (United States)

    Choudhury, Rajib; Barman, Arghya; Prabhakar, Rajeev; Ramamurthy, V

    2013-01-10

    In this study we have examined the conformational preference of phenyl-substituted hydrocarbons (alkanes, alkenes, and alkynes) of different chain lengths included within a confined space provided by a molecular capsule made of two host cavitands known by the trivial name "octa acid" (OA). One- and two-dimensional (1)H NMR experiments and molecular dynamics (MD) simulations were employed to probe the location and conformation of hydrocarbons within the OA capsule. In general, small hydrocarbons adopted a linear conformation while longer ones preferred a folded conformation. In addition, the extent of folding and the location of the end groups (methyl and phenyl) were dependent on the group (H(2)C-CH(2), HC═CH, and C≡C) adjacent to the phenyl group. In addition, the rotational mobility of the hydrocarbons within the capsule varied; for example, while phenylated alkanes tumbled freely, phenylated alkenes and alkynes resisted such a motion at room temperature. Combined NMR and MD simulation studies have confirmed that molecules could adopt conformations within confined spaces different from that in solution, opening opportunities to modulate chemical behavior of guest molecules.

  10. Conformational Ensemble of hIAPP Dimer: Insight into the Molecular Mechanism by which a Green Tea Extract inhibits hIAPP Aggregation.

    Science.gov (United States)

    Mo, Yuxiang; Lei, Jiangtao; Sun, Yunxiang; Zhang, Qingwen; Wei, Guanghong

    2016-01-01

    Small oligomers formed early along human islet amyloid polypeptide (hIAPP) aggregation is responsible for the cell death in Type II diabetes. The epigallocatechin gallate (EGCG), a green tea extract, was found to inhibit hIAPP fibrillation. However, the inhibition mechanism and the conformational distribution of the smallest hIAPP oligomer - dimer are mostly unknown. Herein, we performed extensive replica exchange molecular dynamic simulations on hIAPP dimer with and without EGCG molecules. Extended hIAPP dimer conformations, with a collision cross section value similar to that observed by ion mobility-mass spectrometry, were observed in our simulations. Notably, these dimers adopt a three-stranded antiparallel β-sheet and contain the previously reported β-hairpin amyloidogenic precursor. We find that EGCG binding strongly blocks both the inter-peptide hydrophobic and aromatic-stacking interactions responsible for inter-peptide β-sheet formation and intra-peptide interaction crucial for β-hairpin formation, thus abolishes the three-stranded β-sheet structures and leads to the formation of coil-rich conformations. Hydrophobic, aromatic-stacking, cation-π and hydrogen-bonding interactions jointly contribute to the EGCG-induced conformational shift. This study provides, on atomic level, the conformational ensemble of hIAPP dimer and the molecular mechanism by which EGCG inhibits hIAPP aggregation. PMID:27620620

  11. High-Molecular-Weight Proanthocyanidins in Foods: Overcoming Analytical Challenges in Pursuit of Novel Dietary Bioactive Components.

    Science.gov (United States)

    Neilson, Andrew P; O'Keefe, Sean F; Bolling, Bradley W

    2016-01-01

    Proanthocyanidins (PACs) are an abundant but complex class of polyphenols found in foods and botanicals. PACs are polymeric flavanols with a variety of linkages and subunits. Connectivity and degree of polymerization (DP) determine PAC bioavailability and bioactivity. Current quantitative and qualitative methods may ignore a large percentage of dietary PACs. Subsequent correlations between intake and activity are hindered by a lack of understanding of the true PAC complexity in many foods. Additionally, estimates of dietary intakes are likely inaccurate, as nutrient databank values are largely based on standards from cocoa (monomers to decamers) and blueberries (mean DP of 36). Improved analytical methodologies are needed to increase our understanding of the biological roles of these complex compounds. PMID:26735794

  12. Probing the ATP-induced conformational flexibility of the PcrA helicase protein using molecular dynamics simulation.

    Science.gov (United States)

    Mhashal, Anil R; Choudhury, Chandan Kumar; Roy, Sudip

    2016-03-01

    Helicases are enzymes that unwind double-stranded DNA (dsDNA) into its single-stranded components. It is important to understand the binding and unbinding of ATP from the active sites of helicases, as this knowledge can be used to elucidate the functionality of helicases during the unwinding of dsDNA. In this work, we investigated the unbinding of ATP and its effect on the active-site residues of the helicase PcrA using molecular dynamic simulations. To mimic the unbinding process of ATP from the active site of the helicase, we simulated the application of an external force that pulls ATP from the active site and computed the free-energy change during this process. We estimated an energy cost of ~85 kJ/mol for the transformation of the helicase from the ATP-bound state (1QHH) to the ATP-free state (1PJR). Unbinding led to conformational changes in the residues of the protein at the active site. Some of the residues at the ATP-binding site were significantly reoriented when the ATP was pulled. We observed a clear competition between reorientation of the residues and energy stabilization by hydrogen bonds between the ATP and active-site residues. We also checked the flexibility of the PcrA protein using a principal component analysis of domain motion. We found that the ATP-free state of the helicase is more flexible than the ATP-bound state. PMID:26860503

  13. Molecular effects of bioactive fraction of Curcuma mangga (DLBS4847 as a downregulator of 5α-reductase activity pathways in prostatic epithelial cells

    Directory of Open Access Journals (Sweden)

    Karsono AH

    2014-06-01

    Full Text Available Agung Heru Karsono, Olivia Mayasari Tandrasasmita, Raymond R TjandrawinataSection of Molecular Pharmacology, Research Innovation and Invention, Dexa Laboratories of Biomolecular Sciences, Dexa Medica, Cikarang, IndonesiaAbstract: DLBS4847 is a standardized bioactive fraction of Curcuma mangga. In this study, we used prostate cancer (PC-3 as the cell line to study the effects of DLBS4847 on prostatic cell viability, as well as related molecular changes associated with the decreased cell number. The observation revealed that DLBS4847 inhibited the growth of PC3 cells through downregulation of the 5α-reductase (5AR pathway. At the transcription level, 5AR1 and androgen-receptor gene expressions were downregulated in a dose-dependent manner. Furthermore, 5AR-1 and dihydrotestosterone expression were also downregulated at the protein level. A microarray study was also performed to see the effects of DLBS4847 on differential gene expressions in prostate cancer 3 cells. Among others, DLBS4847 downregulated genes related to prostate growth and hypertrophy. Our results suggested that DLBS4847 could potentially become an alternative treatment for prostate disorders, such as benign prostatic hyperplasia. In this regard, DLBS4847 exerts its growth inhibition partially through downregulation of the 5AR pathway.Keywords: DLBS4847, Curcuma mangga, 5α-reductase inhibitor, benign prostatic hyperplasia (BPH, prostate cancer

  14. Backbone conformational flexibility of the lipid modified membrane anchor of the human N-Ras protein investigated by solid-state NMR and molecular dynamics simulation.

    Science.gov (United States)

    Vogel, Alexander; Reuther, Guido; Roark, Matthew B; Tan, Kui-Thong; Waldmann, Herbert; Feller, Scott E; Huster, Daniel

    2010-02-01

    The lipid modified human N-Ras protein, implicated in human cancer development, is of particular interest due to its membrane anchor that determines the activity and subcellular location of the protein. Previous solid-state NMR investigations indicated that this membrane anchor is highly dynamic, which may be indicative of backbone conformational flexibility. This article aims to address if a dynamic exchange between three structural models exist that had been determined previously. We applied a combination of solid-state nuclear magnetic resonance (NMR) methods and replica exchange molecular dynamics (MD) simulations using a Ras peptide that represents the terminal seven amino acids of the human N-Ras protein. Analysis of correlations between the conformations of individual amino acids revealed that Cys 181 and Met 182 undergo collective conformational exchange. Two major structures constituting about 60% of all conformations could be identified. The two conformations found in the simulation are in rapid exchange, which gives rise to low backbone order parameters and nuclear spin relaxation as measured by experimental NMR methods. These parameters were also determined from two 300 ns conventional MD simulations, providing very good agreement with the experimental data. PMID:19819220

  15. Bioactive compounds from culinary herbs inhibit a molecular target for type 2 diabetes management, dipeptidyl peptidase IV.

    Science.gov (United States)

    Bower, Allyson M; Real Hernandez, Luis M; Berhow, Mark A; de Mejia, Elvira Gonzalez

    2014-07-01

    Greek oregano (Origanum vulgare), marjoram (Origanum majorana), rosemary (Rosmarinus officinalis), and Mexican oregano (Lippia graveolens) are concentrated sources of bioactive compounds. The aims were to characterize and examine extracts from greenhouse-grown or commercially purchased herbs for their ability to inhibit dipeptidyl peptidase IV (DPP-IV) and protein tyrosine phosphatase 1B (PTP1B), enzymes that play a role in insulin secretion and insulin signaling, respectively. Greenhouse herbs contained more polyphenols (302.7-430.1 μg of gallic acid equivalents/mg of dry weight of extract (DWE)) and flavonoids (370.1-661.4 μg of rutin equivalents/mg of DWE) compared to the equivalent commercial herbs. Greenhouse rosemary, Mexican oregano, and marjoram extracts were the best inhibitors of DPP-IV (IC₅₀=16, 29, and 59 μM, respectively). Commercial rosemary, Mexican oregano, and marjoram were the best inhibitors of PTP1B (32.4-40.9% at 500 μM). The phytochemicals eriodictyol, naringenin, hispidulin, cirsimaritin, and carnosol were identified by LC-ESI-MS as being present in greenhouse-grown Mexican oregano and rosemary. Computational modeling indicated that hispidulin, carnosol, and eriodictyol would have the best binding affinities for DPP-IV. Biochemically, the best inhibitors of DPP-IV were cirsimaritin (IC₅₀=0.43±0.07 μM), hispidulin (IC₅₀=0.49±0.06 μM), and naringenin (IC₅₀=2.5±0.29 μM). Overall, herbs contain several flavonoids that inhibit DPP-IV and should be investigated further regarding their potential in diabetes management. PMID:24881464

  16. Rescuing compound bioactivity in a secondary cell-based screening by using γ-cyclodextrin as a molecular carrier

    Science.gov (United States)

    Claveria-Gimeno, Rafael; Vega, Sonia; Grazu, Valeria; de la Fuente, Jesús M; Lanas, Angel; Velazquez-Campoy, Adrian; Abian, Olga

    2015-01-01

    In vitro primary screening for identifying bioactive compounds (inhibitors, activators or pharmacological chaperones) against a protein target results in the discovery of lead compounds that must be tested in cell-based efficacy secondary screenings. Very often lead compounds do not succeed because of an apparent low potency in cell assays, despite an excellent performance in primary screening. Primary and secondary screenings differ significantly according to the conditions and challenges the compounds must overcome in order to interact with their intended target. Cellular internalization and intracellular metabolism are some of the difficulties the compounds must confront and different strategies can be envisaged for minimizing that problem. Using a novel screening procedure we have identified 15 compounds inhibiting the hepatitis C NS3 protease in an allosteric fashion. After characterizing biophysically the interaction with the target, some of the compounds were not able to inhibit viral replication in cell assays. In order to overcome this obstacle and potentially improve cellular internalization three of these compounds were complexed with γ-cyclodextrin. Two of them showed a five- and 16-fold activity increase, compared to their activity when delivered as free compounds in solution (while γ-cyclodextrin did not show antiviral activity by itself). The most remarkable result came from a third compound that showed no antiviral activity in cell assays when delivered free in solution, but its γ-cyclodextrin complex exhibited a 50% effective concentration of 5 μM. Thus, the antiviral activity of these compounds can be significantly improved, even completely rescued, using γ-cyclodextrin as carrier molecule. PMID:25834436

  17. Shape: automatic conformation prediction of carbohydrates using a genetic algorithm

    Directory of Open Access Journals (Sweden)

    Rosen Jimmy

    2009-09-01

    Full Text Available Abstract Background Detailed experimental three dimensional structures of carbohydrates are often difficult to acquire. Molecular modelling and computational conformation prediction are therefore commonly used tools for three dimensional structure studies. Modelling procedures generally require significant training and computing resources, which is often impractical for most experimental chemists and biologists. Shape has been developed to improve the availability of modelling in this field. Results The Shape software package has been developed for simplicity of use and conformation prediction performance. A trivial user interface coupled to an efficient genetic algorithm conformation search makes it a powerful tool for automated modelling. Carbohydrates up to a few hundred atoms in size can be investigated on common computer hardware. It has been shown to perform well for the prediction of over four hundred bioactive oligosaccharides, as well as compare favourably with previously published studies on carbohydrate conformation prediction. Conclusion The Shape fully automated conformation prediction can be used by scientists who lack significant modelling training, and performs well on computing hardware such as laptops and desktops. It can also be deployed on computer clusters for increased capacity. The prediction accuracy under the default settings is good, as it agrees well with experimental data and previously published conformation prediction studies. This software is available both as open source and under commercial licenses.

  18. Characterization of molecular determinants of the conformational stability of macrophage migration inhibitory factor: leucine 46 hydrophobic pocket.

    Directory of Open Access Journals (Sweden)

    Farah El-Turk

    Full Text Available Macrophage Migration Inhibitory Factor (MIF is a key mediator of inflammatory responses and innate immunity and has been implicated in the pathogenesis of several inflammatory and autoimmune diseases. The oligomerization of MIF, more specifically trimer formation, is essential for its keto-enol tautomerase activity and probably mediates several of its interactions and biological activities, including its binding to its receptor CD74 and activation of certain signaling pathways. Therefore, understanding the molecular factors governing the oligomerization of MIF and the role of quaternary structure in modulating its structural stability and multifunctional properties is crucial for understanding the function of MIF in health and disease. Herein, we describe highly conserved intersubunit interactions involving the hydrophobic packing of the side chain of Leu46 onto the β-strand β3 of one monomer within a hydrophobic pocket from the adjacent monomer constituted by residues Arg11, Val14, Phe18, Leu19, Val39, His40, Val41, Val42, and Pro43. To elucidate the structural significance of these intersubunit interactions and their relative contribution to MIF's trimerization, structural stability and catalytic activity, we generated three point mutations where Leu46 was replaced by glycine (L46G, alanine (L46A and phenylalanine (L46F, and their structural properties, stability, oligomerization state, and catalytic activity were characterized using a battery of biophysical methods and X-ray crystallography. Our findings provide new insights into the role of the Leu46 hydrophobic pocket in stabilizing the conformational state of MIF in solution. Disrupting the Leu46 hydrophobic interaction perturbs the secondary and tertiary structure of the protein but has no effect on its oligomerization state.

  19. Molecular Simulations of Dodecyl-β-maltoside Micelles in Water: Influence of the Headgroup Conformation and Force field Parameters

    Science.gov (United States)

    Abel, Stéphane; Dupradeau, François-Yves; Raman, E. Prabhu; MacKerell, Alexander D.; Marchi, Massimo

    2011-01-01

    This paper deals with the development and validation of new potential parameter sets, based on the CHARMM36 and GLYCAM06 force fields, to simulate micelles of the two anomeric forms (α and β) of N-Dodecyl-ß-maltoside (C12G2), a surfactant widely used in the extraction and purification of membrane proteins. In this context, properties such as size, shape, internal structure and hydration of the C12G2 anomer micelles were thoroughly investigated by molecular dynamics simulations and the results compared with experiments. Additional simulations were also performed with the older CHARMM22 force field for carbohydrates (Kuttel, M. et al. J. Comp. Chem. 2002, 23, 1236-1243). We find that our CHARMM and GLYCAM parameter sets yields similar results in case of properties related to the micelle structure, but differ for other properties such as the headgroup conformation or the micelle hydration. In agreement with experiments, our results show that for all model potentials the β-C12G2 micelles have a more pronounced ellipsoidal shape than those containing α anomers. The computed radius of gyration is 20.2 Å and 25.4 Å for the α- and β-anomer micelles, respectively. Finally, we show that depending on the potential the water translational diffusion of the interfacial water is 7 - 11.5 times slower than that of bulk water due to the entrapment of the water in the micelle crevices. This retardation is independent of the headgroup in α- or β- anomers. PMID:21192681

  20. Bioactivity of chemically transformed humic matter from vermicompost on plant root growth.

    Science.gov (United States)

    Dobbss, Leonardo Barros; Pasqualoto Canellas, Luciano; Lopes Olivares, Fábio; Oliveira Aguiar, Natália; Peres, Lázaro Eustáquio Pereira; Azevedo, Mariana; Spaccini, Riccardo; Piccolo, Alessandro; Façanha, Arnoldo R

    2010-03-24

    Chemical reactions (hydrolysis, oxidation, reduction, methylation, alkyl compounds detachment) were applied to modify the structure of humic substances (HS) isolated from vermicompost. Structural and conformational changes of these humic derivatives were assessed by elemental analyses, size exclusion chromatography (HPSEC), solid-state nuclear magnetic resonance ((13)C CPMAS-NMR), and diffusion ordered spectroscopy (DOSY-NMR), whereas their bioactivity was evaluated by changes in root architecture and proton pump activation of tomato and maize. All humic derivatives exhibited a large bioactivity compared to original HS, both KMnO(4)-oxidized and methylated materials being the most effective. Whereas no general relationship was found between bioactivity and humic molecular sizes, the hydrophobicity index was significantly related with proton pump stimulation. It is suggested that the hydrophobic domain can preserve bioactive molecules such as auxins in the humic matter. In contact with root-exuded organic acids the hydrophobic weak forces could be disrupted, releasing bioactive compounds from humic aggregates. These findings were further supported by the fact that HS and all derivatives used in this study activated the auxin synthetic reporter DR5::GUS. PMID:20232906

  1. Reproducing the conformations of protein-bound ligands: a critical evaluation of several popular conformational searching tools.

    Science.gov (United States)

    Boström, J

    2001-12-01

    Several programs (Catalyst, Confort, Flo99, MacroModel, and Omega) that are commonly used to generate conformational ensembles have been tested for their ability to reproduce bioactive conformations. The ligands from thirty-two different ligand-protein complexes determined by high-resolution (Confort) performed least well. For the seven ligands in the set having eight or more rotatable bonds, none of the bioactive conformations were ever found, save for one exception (Flo99). These ligands do not bind in a local minimum conformation according to AMBER*\\GB/SA. Taking these last two observations together, it is clear that geometrically similar structures should be collected in order to increase the probability of finding the bioactive conformation among the generated ensembles. Factors influencing bioactive conformational retrieval have been identified and are discussed. PMID:12160095

  2. Reproducing the conformations of protein-bound ligands: a critical evaluation of several popular conformational searching tools.

    Science.gov (United States)

    Boström, J

    2001-12-01

    Several programs (Catalyst, Confort, Flo99, MacroModel, and Omega) that are commonly used to generate conformational ensembles have been tested for their ability to reproduce bioactive conformations. The ligands from thirty-two different ligand-protein complexes determined by high-resolution (Confort) performed least well. For the seven ligands in the set having eight or more rotatable bonds, none of the bioactive conformations were ever found, save for one exception (Flo99). These ligands do not bind in a local minimum conformation according to AMBER*\\GB/SA. Taking these last two observations together, it is clear that geometrically similar structures should be collected in order to increase the probability of finding the bioactive conformation among the generated ensembles. Factors influencing bioactive conformational retrieval have been identified and are discussed.

  3. Non-destructive analysis of the conformational differences among feedstock sources and their corresponding co-products from bioethanol production with molecular spectroscopy

    Science.gov (United States)

    Gamage, I. H.; Jonker, A.; Zhang, X.; Yu, P.

    2014-01-01

    The objective of this study was to determine the possibility of using molecular spectroscopy with multivariate technique as a fast method to detect the source effects among original feedstock sources of wheat and their corresponding co-products, wheat DDGS, from bioethanol production. Different sources of the bioethanol feedstock and their corresponding bioethanol co-products, three samples per source, were collected from the same newly-built bioethanol plant with current bioethanol processing technology. Multivariate molecular spectral analyses were carried out using agglomerative hierarchical cluster analysis (AHCA) and principal component analysis (PCA). The molecular spectral data of different feedstock sources and their corresponding co-products were compared at four different regions of ca. 1800-1725 cm-1 (carbonyl Cdbnd O ester, mainly related to lipid structure conformation), ca. 1725-1482 cm-1 (amide I and amide II region mainly related to protein structure conformation), ca. 1482-1180 cm-1 (mainly associated with structural carbohydrate) and ca. 1180-800 cm-1 (mainly related to carbohydrates) in complex plant-based system. The results showed that the molecular spectroscopy with multivariate technique could reveal the structural differences among the bioethanol feedstock sources and among their corresponding co-products. The AHCA and PCA analyses were able to distinguish the molecular structure differences associated with chemical functional groups among the different sources of the feedstock and their corresponding co-products. The molecular spectral differences indicated the differences in functional, biomolecular and biopolymer groups which were confirmed by wet chemical analysis. These biomolecular and biopolymer structural differences were associated with chemical and nutrient profiles and nutrient utilization and availability. Molecular spectral analyses had the potential to identify molecular structure difference among bioethanol feedstock sources

  4. Molecular effects of bioactive fraction of Curcuma mangga (DLBS4847) as a downregulator of 5α-reductase activity pathways in prostatic epithelial cells.

    Science.gov (United States)

    Karsono, Agung Heru; Tandrasasmita, Olivia Mayasari; Tjandrawinata, Raymond R

    2014-01-01

    DLBS4847 is a standardized bioactive fraction of Curcuma mangga. In this study, we used prostate cancer (PC)-3 as the cell line to study the effects of DLBS4847 on prostatic cell viability, as well as related molecular changes associated with the decreased cell number. The observation revealed that DLBS4847 inhibited the growth of PC3 cells through downregulation of the 5α-reductase (5AR) pathway. At the transcription level, 5AR1 and androgen-receptor gene expressions were downregulated in a dose-dependent manner. Furthermore, 5AR-1 and dihydrotestosterone expression were also downregulated at the protein level. A microarray study was also performed to see the effects of DLBS4847 on differential gene expressions in prostate cancer 3 cells. Among others, DLBS4847 downregulated genes related to prostate growth and hypertrophy. Our results suggested that DLBS4847 could potentially become an alternative treatment for prostate disorders, such as benign prostatic hyperplasia. In this regard, DLBS4847 exerts its growth inhibition partially through downregulation of the 5AR pathway.

  5. The SRAP based molecular diversity related to antifungal and antioxidant bioactive constituents for biocontrol potentials of Trichoderma against Sclerotium rolfsii Scc.

    Science.gov (United States)

    Hirpara, Darshna G; Gajera, H P; Bhimani, R D; Golakiya, B A

    2016-08-01

    The study was performed to examine 11 isolates of Trichoderma for their bio-control potentials against Sclerotium rolfsii Sacc. causing stem rot in groundnut. The antagonists Trichoderma were subjected to sequence related amplified polymorphism (SRAP) based molecular diversity analysis and compared with their hardness to S. rolfsii with respect to secretary antifungal and antioxidant profile. T. virens NBAII Tvs 12 evident highest (87.91 %) growth inhibition of test pathogen followed by T. koningii MTCC 796 (67.03 %) at 7 days after inoculation (DAI). Microscopic study confirmed biocontrol mechanism as mycoparasitism for Tvs 12 and antibiosis for MTCC 796. The growth inhibition of test pathogen was significantly negatively correlated with sclerotia formation and lipid peroxidation during antagonism due to release of secretary bioactive antioxidants by antagonists to terminate oxidative burst generated by S. rolfsii and causing inhibition of sclerotium formation. The GC-MS profile identified antifungal and antioxidant constituents hexadecane, 1,2-benzenedicarboxylic acid, mono (2-ethylhexyl) ester, 1-hexadecanesulfonyl chloride, and octadecane in potent antagonists Tvs 12; and nonacosane and octadecane in MTCC 796 along with two novel compounds 1-pentadecene and 1-heneicosyl formate for biocontrol activity. Molecular diversity of Trichoderma isolates associated with antagonistic activity was assessed by SRAP markers. The 115 primer combinations generate total 1328 amplified products of which, 1095 are shared polymorphic and 199 are unique polymorphic. The 15 SRAP combinations produced 18 bands to diagnose best antagonist Tvs 12 and 13 SRAP combinations generated 19 unique bands for identification of MTCC 796. The mycoparasitic antagonist Tvs 12 would be the best antagonist and released unique antifungal and antioxidant constituents to combat pathogen infection. The SRAP based genetic diversity indicates Tvs12 strain clustered with T. viride NBAII Tv23 and shared

  6. {sup 13}CHD{sub 2}–CEST NMR spectroscopy provides an avenue for studies of conformational exchange in high molecular weight proteins

    Energy Technology Data Exchange (ETDEWEB)

    Rennella, Enrico; Huang, Rui; Velyvis, Algirdas; Kay, Lewis E., E-mail: kay@pound.med.utoronto.ca [The University of Toronto, Departments of Molecular Genetics, Biochemistry and Chemistry (Canada)

    2015-10-15

    An NMR experiment for quantifying slow (millisecond) time-scale exchange processes involving the interconversion between visible ground state and invisible, conformationally excited state conformers is presented. The approach exploits chemical exchange saturation transfer (CEST) and makes use of {sup 13}CHD{sub 2} methyl group probes that can be readily incorporated into otherwise highly deuterated proteins. The methodology is validated with an application to a G48A Fyn SH3 domain that exchanges between a folded conformation and a sparsely populated and transiently formed unfolded ensemble. Experiments on a number of different protein systems, including a 360 kDa half-proteasome, establish that the sensitivity of this {sup 13}CHD{sub 2}{sup 13}C–CEST technique can be upwards of a factor of 5 times higher than for a previously published {sup 13}CH{sub 3}{sup 13}C–CEST approach (Bouvignies and Kay in J Biomol NMR 53:303–310, 2012), suggesting that the methodology will be powerful for studies of conformational exchange in high molecular weight proteins.

  7. Structural, conformational, and theoretical binding studies of antitumor antibiotic porfiromycin (N-methylmitomycin C), a covalent binder of DNA, by X-ray, NMR, and molecular mechanics.

    Science.gov (United States)

    Arora, S K; Cox, M B; Arjunan, P

    1990-11-01

    X-ray, NMR, and molecular mechanics studies on antitumor antibiotic porfiromycin (C16H20N4O5), a covalent binder of DNA, have been carried out to study the structure, conformation, and theoretical interactions with DNA. The crystal structure was solved by direct methods and refined to an R value of 0.052. The configurations at C(9), C(9a), C(1), and C(2) are S, R, S, and S, except for the orientation of the aziridine ring and (carbamoyloxy)methyl side chain. The five-membered ring attached to the aziridine ring adopts an envelope conformation. The solution conformation is similar to that observed in the solid state except for the (carbamoyloxy)methyl side chain. Monovalent and cross-linked models of the drug bound to DNA have been energetically refined by using molecular mechanics. The results indicate that, in the case of monocovalent binding, the drug clearly prefers a d(CpG) sequence rather than a d(GpC) sequence. In the case of the cross-linked model there is no clear-cut preference of d(CpG) over d(GpC), indicating that the binding preference of the drug may be kinetic rather than thermodynamic. PMID:2231597

  8. Conformational analysis, spectroscopic study (FT-IR, FT-Raman, UV, 1H and 13C NMR), molecular orbital energy and NLO properties of 5-iodosalicylic acid

    Science.gov (United States)

    Karaca, Caglar; Atac, Ahmet; Karabacak, Mehmet

    2015-02-01

    In this study, 5-iodosalicylic acid (5-ISA, C7H5IO3) is structurally characterized by FT-IR, FT-Raman, NMR and UV spectroscopies. There are eight conformers, Cn, n = 1-8 for this molecule therefore the molecular geometry for these eight conformers in the ground state are calculated by using the ab-initio density functional theory (DFT) B3LYP method approach with the aug-cc-pVDZ-PP basis set for iodine and the aug-cc-pVDZ basis set for the other elements. The computational results identified that the most stable conformer of 5-ISA is the C1 form. The vibrational spectra are calculated DFT method invoking the same basis sets and fundamental vibrations are assigned on the basis of the total energy distribution (TED) of the vibrational modes, calculated with scaled quantum mechanics (SQM) method with PQS program. Total density of state (TDOS) and partial density of state (PDOS) and also overlap population density of state (COOP or OPDOS) diagrams analysis for C1 conformer were calculated using the same method. The energy and oscillator strength are calculated by time-dependent density functional theory (TD-DFT) results complement with the experimental findings. Besides, charge transfer occurring in the molecule between HOMO and LUMO energies, frontier energy gap, molecular electrostatic potential (MEP) are calculated and presented. The NMR chemical shifts (1H and 13C) spectra are recorded and calculated using the gauge independent atomic orbital (GIAO) method. Mulliken atomic charges of the title molecule are also calculated, interpreted and compared with salicylic acid. The optimized bond lengths, bond angles and calculated NMR and UV, vibrational wavenumbers showed the best agreement with the experimental results.

  9. Conformational sensitivity of conjugated poly(ethylene oxide)-poly(amidoamine) molecules to cations adducted upon electrospray ionization – A mass spectrometry, ion mobility and molecular modeling study

    Energy Technology Data Exchange (ETDEWEB)

    Tintaru, Aura [Aix-Marseille Université – CNRS, UMR 7273, Institut de Chimie Radicalaire, Marseille (France); Chendo, Christophe [Aix-Marseille Université – CNRS, FR 1739, Fédération des Sciences Chimiques de Marseille, Spectropole, Marseille (France); Wang, Qi [Aix-Marseille Université – CNRS, UMR 6114, Centre Interdisciplinaire de Nanosciences de Marseille, Marseille (France); Viel, Stéphane [Aix-Marseille Université – CNRS, UMR 7273, Institut de Chimie Radicalaire, Marseille (France); Quéléver, Gilles; Peng, Ling [Aix-Marseille Université – CNRS, UMR 6114, Centre Interdisciplinaire de Nanosciences de Marseille, Marseille (France); Posocco, Paola [University of Trieste, Molecular Simulation Engineering (MOSE) Laboratory, Department of Engineering and Architecture (DEA), Trieste (Italy); National Interuniversity Consortium for Material Science and Technology (INSTM), Research Unit MOSE-DEA, University of Trieste, Trieste (Italy); Pricl, Sabrina, E-mail: sabrina.pricl@di3.units.it [University of Trieste, Molecular Simulation Engineering (MOSE) Laboratory, Department of Engineering and Architecture (DEA), Trieste (Italy); National Interuniversity Consortium for Material Science and Technology (INSTM), Research Unit MOSE-DEA, University of Trieste, Trieste (Italy); Charles, Laurence, E-mail: laurence.charles@univ-amu.fr [Aix-Marseille Université – CNRS, UMR 7273, Institut de Chimie Radicalaire, Marseille (France)

    2014-01-15

    Graphical abstract: -- Highlights: •ESI-MS/MS, IMS and molecular modeling were combined to study PEO-PAMAM conformation. •Protonated and lithiated molecules were studied, with charge states from 2 to 4. •Protonation mostly occurred on PAMAM, with PEO units enclosing the protonated group. •Lithium adduction on PEO units lead to more expanded conformations. •Charge location strongly influenced PEO-PAMAM dissociation behavior. -- Abstract: Tandem mass spectrometry and ion mobility spectrometry experiments were performed on multiply charged molecules formed upon conjugation of a poly(amidoamine) (PAMAM) dendrimer with a poly(ethylene oxide) (PEO) linear polymer to evidence any conformational modification as a function of their charge state (2+ to 4+) and of the adducted cation (H{sup +}vs Li{sup +}). Experimental findings were rationalized by molecular dynamics simulations. The G0 PAMAM head-group could accommodate up to three protons, with protonated terminal amine group enclosed in a pseudo 18-crown-6 ring formed by the PEO segment. This particular conformation enabled a hydrogen bond network which allowed long-range proton transfer to occur during collisionally activated dissociation. In contrast, lithium adduction was found to mainly occur onto oxygen atoms of the polyether, each Li{sup +} cation being coordinated by a 12-crown-4 pseudo structure. As a result, for the studied polymeric segment (M{sub n} = 1500 g mol{sup −1}), PEO-PAMAM hybrid molecules exhibited a more expanded shape when adducted to lithium as compared to proton.

  10. New Insights into Active Site Conformation Dynamics of E. coli PNP Revealed by Combined H/D Exchange Approach and Molecular Dynamics Simulations

    Science.gov (United States)

    Kazazić, Saša; Bertoša, Branimir; Luić, Marija; Mikleušević, Goran; Tarnowski, Krzysztof; Dadlez, Michal; Narczyk, Marta; Bzowska, Agnieszka

    2016-01-01

    The biologically active form of purine nucleoside phosphorylase (PNP) from Escherichia coli (EC 2.4.2.1) is a homohexamer unit, assembled as a trimer of dimers. Upon binding of phosphate, neighboring monomers adopt different active site conformations, described as open and closed. To get insight into the functions of the two distinctive active site conformations, virtually inactive Arg24Ala mutant is complexed with phosphate; all active sites are found to be in the open conformation. To understand how the sites of neighboring monomers communicate with each other, we have combined H/D exchange (H/DX) experiments with molecular dynamics (MD) simulations. Both methods point to the mobility of the enzyme, associated with a few flexible regions situated at the surface and within the dimer interface. Although H/DX provides an average extent of deuterium uptake for all six hexamer active sites, it was able to indicate the dynamic mechanism of cross-talk between monomers, allostery. Using this technique, it was found that phosphate binding to the wild type (WT) causes arrest of the molecular motion in backbone fragments that are flexible in a ligand-free state. This was not the case for the Arg24Ala mutant. Upon nucleoside substrate/inhibitor binding, some release of the phosphate-induced arrest is observed for the WT, whereas the opposite effects occur for the Arg24Ala mutant. MD simulations confirmed that phosphate is bound tightly in the closed active sites of the WT; conversely, in the open conformation of the active site of the WT phosphate is bound loosely moving towards the exit of the active site. In Arg24Ala mutant binary complex Pi is bound loosely, too.

  11. Is conformation a fundamental descriptor in QSAR? A case for halogenated anesthetics

    Science.gov (United States)

    Guimarães, Maria C; Duarte, Mariene H; Silla, Josué M

    2016-01-01

    Summary An intriguing question in 3D-QSAR lies on which conformation(s) to use when generating molecular descriptors (MD) for correlation with bioactivity values. This is not a simple task because the bioactive conformation in molecule data sets is usually unknown and, therefore, optimized structures in a receptor-free environment are often used to generate the MD´s. In this case, a wrong conformational choice can cause misinterpretation of the QSAR model. The present computational work reports the conformational analysis of the volatile anesthetic isoflurane (2-chloro-2-(difluoromethoxy)-1,1,1-trifluoroethane) in the gas phase and also in polar and nonpolar implicit and explicit solvents to show that stable minima (ruled by intramolecular interactions) do not necessarily coincide with the bioconformation (ruled by enzyme induced fit). Consequently, a QSAR model based on two-dimensional chemical structures was built and exhibited satisfactory modeling/prediction capability and interpretability, then suggesting that these 2D MD´s can be advantageous over some three-dimensional descriptors. PMID:27340468

  12. Enzymatic induction of supramolecular order and bioactivity

    Science.gov (United States)

    Yang, Chengbiao; Ren, Xinrui; Ding, Dan; Wang, Ling; Yang, Zhimou

    2016-05-01

    We showed in this study that enzymatic triggering is a totally different pathway for the preparation of self-assembling nanomaterials to the heating-cooling process. Because the molecules were under lower energy levels and the molecular conformation was more ordered during the enzymatic triggeration under mild conditions, nanomaterials with higher supramolecular order could be obtained through biocatalytic control. In this study, nanoparticles were obtained by an enzymatic reaction and nanofibers were observed through the heating-cooling process. We observed a distinct trough at 318 nm from the CD spectrum of a particle sample but not a fiber sample, suggesting the long range arrangement of molecules and helicity in the nanoparticles. The nanoparticles with higher supramolecular order possessed much better potency as a protein vaccine adjuvant because it accelerated the DC maturation and elicited stronger T-cells cytokine production than the nanofibers. Our study demonstrated that biocatalytic triggering is a useful method for preparing supramolecular nanomaterials with higher supramolecular order and probably better bioactivity.We showed in this study that enzymatic triggering is a totally different pathway for the preparation of self-assembling nanomaterials to the heating-cooling process. Because the molecules were under lower energy levels and the molecular conformation was more ordered during the enzymatic triggeration under mild conditions, nanomaterials with higher supramolecular order could be obtained through biocatalytic control. In this study, nanoparticles were obtained by an enzymatic reaction and nanofibers were observed through the heating-cooling process. We observed a distinct trough at 318 nm from the CD spectrum of a particle sample but not a fiber sample, suggesting the long range arrangement of molecules and helicity in the nanoparticles. The nanoparticles with higher supramolecular order possessed much better potency as a protein vaccine

  13. The future of bioactive ceramics.

    Science.gov (United States)

    Hench, Larry L

    2015-02-01

    Two important worldwide needs must be satisfied in the future; (1) treatment of the deteriorating health of an aging population and, (2) decreasing healthcare costs to meet the needs of an increased population. The ethical and economic dilemma is how to achieve equality in quality of care while at the same time decreasing cost of care for an ever-expanding number of people. The limited lifetime of prosthetic devices made from first-generation nearly inert biomaterials requires new approaches to meet these two large needs. This paper advises an expanded emphasis on: (1) regeneration of tissues and (2) prevention of tissue deterioration to meet this growing need. Innovative use of bioactive ceramics with genetic control of in situ tissue responses offers the potential to achieve both tissue regeneration and prevention. Clinical success of use of bioactive glass for bone regeneration is evidence that this concept works. Likewise the use of micron sized bioactive glass powders in a dentifrice for re-mineralization of teeth provides evidence that prevention of tissue deterioration is also possible. This opinion paper outlines clinical needs that could be met by innovative use of bioactive glasses and ceramics in the near future; including: regeneration of skeletal tissues that is patient specific and genetic based, load-bearing bioactive glass-ceramics for skeletal and ligament and tendon repair, repair and regeneration of soft tissues, and rapid low-cost analysis of human cell-biomaterial interactions leading to patient specific diagnoses and treatments using molecularly tailored bioceramics.

  14. Grazing incidence X-ray diffraction study of the tilted phases of Langmuir films: Determination of molecular conformations using simulated annealing

    International Nuclear Information System (INIS)

    We have analyzed grazing incidence X-ray diffraction (GIXD) data from condensed phases of Langmuir films of long-chain fatty acids at the air-water using a new method consisting in a careful extraction of the structure factors followed by fitting of molecular parameters using simulated annealing. We show that the information contained in GIXD spectra is enough to obtain near-atomic structural information. In particular, we directly determine the orientation of the chain backbone planes and of the carboxylic headgroups, and we evaluate chain conformation defects

  15. Conformal house

    DEFF Research Database (Denmark)

    Ryttov, Thomas Aaby; Sannino, Francesco

    2010-01-01

    fixed point. As a consistency check we recover the previously investigated bounds of the conformal windows when restricting to a single matter representation. The earlier conformal windows can be imagined to be part now of the new conformal house. We predict the nonperturbative anomalous dimensions...... at the infrared fixed points. We further investigate the effects of adding mass terms to the condensates on the conformal house chiral dynamics and construct the simplest instanton induced effective Lagrangian terms...

  16. Molecular modeling on the recognition of DNA sequence and conformational repair of sheared DNA by novel chiral metal complex D, L-[Co(phen)2hpip]3+

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    A study on the recognition of DNA sequence and conformational repair of sheared DNA by Novel Chiral Metal complex D,L-[Co(phen)2hpip]3+ (phen=1,10 phenanthroline, hpip=2-[2-hydroxyphenyl] imidazole [4,5-f][1,10] phenanthroline) is carried out with molecular simulations. The results reveal that two isomers of the complex could both recognize the normal DNA in the minor groove orientation, while recognize the sheared DNA in the major groove orientation and both isomers could convert the conformation of mismatched bases from sheared form to parallel form. Further analysis shows that the steric details of complex's intercalation to base stack determine the results of recognition, which is induced by the steric collision among ancillary ligand phen, bases and DNA backbone, and by the steric crowding occurring in the process of structural expansion of bases and DNA backbone. Detailed analysis reveals that the conformational repair of mismatched bases relates not only to the steric interactions, but also to the π-π stack among normal bases, mismatched bases and hpip ligand.

  17. Conformational Analysis, Molecular Structure and Solid State Simulation of the Antiviral Drug Acyclovir (Zovirax Using Density Functional Theory Methods

    Directory of Open Access Journals (Sweden)

    Margarita Clara Alvarez-Ros

    2014-06-01

    Full Text Available The five tautomers of the drug acyclovir (ACV were determined and optimised at the MP2 and B3LYP quantum chemical levels of theory. The stability of the tautomers was correlated with different parameters. On the most stable tautomer N1 was carried out a comprehensive conformational analysis, and the whole conformational parameters (R, β, Φ, φ1, φ2, φ3, φ4, φ5 were studied as well as the NBO Natural atomic charges. The calculations were carried out with full relaxation of all geometrical parameters. The search located at least 78 stable structures within 8.5 kcal/mol electronic energy range of the global minimum, and classified in two groups according to the positive or negative value of the torsional angle j1. In the nitrogen atoms and in the O2' and O5' oxygen atoms of the most stable conformer appear a higher reactivity than in the natural nucleoside deoxyguanosine. The solid state was simulated through a dimer and tetramer forms and the structural parameters were compared with the X-ray crystal data available. Several general conclusions were emphasized.

  18. Molecular dynamics characterization of the conformational landscape of small peptides: A series of hands-on collaborative practical sessions for undergraduate students.

    Science.gov (United States)

    Rodrigues, João P G L M; Melquiond, Adrien S J; Bonvin, Alexandre M J J

    2016-01-01

    Molecular modelling and simulations are nowadays an integral part of research in areas ranging from physics to chemistry to structural biology, as well as pharmaceutical drug design. This popularity is due to the development of high-performance hardware and of accurate and efficient molecular mechanics algorithms by the scientific community. These improvements are also benefitting scientific education. Molecular simulations, their underlying theory, and their applications are particularly difficult to grasp for undergraduate students. Having hands-on experience with the methods contributes to a better understanding and solidification of the concepts taught during the lectures. To this end, we have created a computer practical class, which has been running for the past five years, composed of several sessions where students characterize the conformational landscape of small peptides using molecular dynamics simulations in order to gain insights on their binding to protein receptors. In this report, we detail the ingredients and recipe necessary to establish and carry out this practical, as well as some of the questions posed to the students and their expected results. Further, we cite some examples of the students' written reports, provide statistics, and share their feedbacks on the structure and execution of the sessions. These sessions were implemented alongside a theoretical molecular modelling course but have also been used successfully as a standalone tutorial during specialized workshops. The availability of the material on our web page also facilitates this integration and dissemination and lends strength to the thesis of open-source science and education. PMID:26751257

  19. Development of Bioactive Edible Coatings and Biodegradable Packaging Using Gamma Irradiation

    International Nuclear Information System (INIS)

    Gamma irradiation was used to cross-link milk proteins in order to enhance the physico-chemical properties of edible films made of calcium caseinate, whey protein isolate and glycerol. Fourier Transform Infrared analysis was used to characterize the conformation of proteins adopted after irradiation. The molecular weight of cross-linked proteins was measured by Size-Exclusion Chromatography. Furthermore, the effect of the addition of methylcellulose to the irradiated protein matrix on the rheological properties (puncture strength, puncture deformation and water vapor permeability) of films was also studied. Moreover, cross-linking of polysaccharides under paste-like state was investigated and the cross-linking degree of the gel products was determined by gel fraction measurements and solubility percentage. In order to prepare bioactive coatings, several antifungal compounds were evaluated as bioactive compounds in order to select one of them to prepare an antimicrobial solution to spray onto strawberries or to encapsulate them in film formulations composed of milk proteins and methylcellulose based films. In addition, the bioactive coatings containing the antifungals were used to increase the radiosensitivity under air of moulds and total flora in strawberries and the relative sensitivity of selected formulations was calculated from their D10 value. The film formulation selected was used as a bioactive edible coating in order to determine their efficiency to increase the shelf life of fresh strawberries and to preserve their quality during storage. (author)

  20. Chain conformational and physicochemical properties of fucoidans from sea cucumber.

    Science.gov (United States)

    Xu, Xiaoqi; Xue, Changhu; Chang, Yaoguang; Wang, Jun; Jiang, Kunhao

    2016-11-01

    Although fucoidans from sea cucumber (SC-FUCs) have been proven as potential bioactive polysaccharides and functional food ingridents, their chain conformation and physicochemical properties were still poorly understood. This study investigated the chain conformation of fucoidans from sea cucumber Acaudina molpadioides (Am-FUC), Isostichopus badionotus (Ib-FUC) and Apostichopus japonicus (Aj-FUC), of which primary structure has been recently clarified. Chain conformation parameters demonstrated that studied SC-FUCs adopted random coil conformation in 150mM NaCl solution (pH 7.4). Based on the worm-like cylinder model and atomic force microscopy, the chain stiffness of SC-FUCs was further evaluated as Am-FUC≈Ib-FUC>Aj-FUC. It was suggested that the existence of branch structure increased the chain flexibility, while sulfated pattern exerted limited influence. SC-FUCs demonstrated shear-thinning rheological behavior and negative charge. Am-FUC possessed a higher thermostability than Ib-FUC and Aj-FUC. These results have important implications for understanding the molecular characteristics of SC-FUCs, which could facilitate their further application. PMID:27516290

  1. Observation and modeling of conformational molecular structures driving the self-assembly of tri-adamantyl benzene on Ag(111).

    Science.gov (United States)

    Calmettes, Bastien; Estrampes, Nicolas; Coudret, Christophe; Roussel, Thomas J; Faraudo, Jordi; Coratger, Roland

    2016-07-27

    The self-organization of tri-adamantyl (TAB) benzene molecules has been investigated using low temperature scanning tunneling microscopy (LT-STM). The molecular structures have also been studied using molecular modeling. In particular, these calculations have been performed on large areas (1000 nm(2)) from the atomic structure of the molecular building block, combining molecular dynamics (MD) and Monte-Carlo (MC) approaches. These investigations show that the structure of the molecule and its flexibility allow for the formation of different networks as a function of surface coverage. The calculations demonstrate that the stability of the largest structures is obtained through the increase of the interfacial energy induced by the rotation of the adamantyl groups, a behavior whose consequences explain the subtle contrasts observed in the experimental STM images. PMID:26667964

  2. Planctomycetes as novel source of bioactive molecules

    Directory of Open Access Journals (Sweden)

    Ana Patrícia Graça

    2016-08-01

    Full Text Available Marine environments are a fruitful source of bioactive compounds some of which are the newest leading drugs in medicinal therapeutics. Of particular importance are organisms like sponges and macroalgae and their associated microbiome. Planctomycetes, abundant in macroalgae biofilms, are promising producers of bioactive compounds since they share characteristics, like large genomes and complex life cycles, with the most bioactive bacteria, the Actinobacteria. Furthermore, genome mining revealed the presence of secondary metabolite pathway genes or clusters in 13 analyzed Planctomycetes genomes.In order to assess the antimicrobial production of a large and diverse collection of Planctomycetes isolated from macroalgae from the Portuguese coast, molecular and bioactivity assays were performed in 40 bacteria from several taxa. Two genes commonly associated with the production of bioactive compounds, nonribosomal peptide synthetases (NRPS and polyketide synthases (PKS genes were screened. Molecular analysis revealed that 95 % of the planctomycetes potentially have one or both secondary bioactive genes; 85 % amplified with PKS-I primers and 55 % with NRPS primers. Some of the amplified genes were confirmed to be involved in secondary metabolite pathways. Using bioinformatic tools their biosynthetic pathways were predicted. The secondary metabolite genomic potential of strains LF1, UC8 and FC18 was assessed using in silico analysis of their genomes. Aqueous and organic extracts of the Planctomycetes were evaluated for their antimicrobial activity against an environmental Escherichia coli, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923, Bacillus subtilis ATCC 6633 and a clinical isolate of Candida albicans. The screening assays showed a high number of planctomycetes with bioactive extracts revealing antifungal (43 % and antibacterial (54 % activity against C. albicans and B. subtilis, respectively

  3. Planctomycetes as Novel Source of Bioactive Molecules.

    Science.gov (United States)

    Graça, Ana P; Calisto, Rita; Lage, Olga M

    2016-01-01

    Marine environments are a fruitful source of bioactive compounds some of which are the newest leading drugs in medicinal therapeutics. Of particular importance are organisms like sponges and macroalgae and their associated microbiome. Planctomycetes, abundant in macroalgae biofilms, are promising producers of bioactive compounds since they share characteristics, like large genomes and complex life cycles, with the most bioactive bacteria, the Actinobacteria. Furthermore, genome mining revealed the presence of secondary metabolite pathway genes or clusters in 13 analyzed Planctomycetes genomes. In order to assess the antimicrobial production of a large and diverse collection of Planctomycetes isolated from macroalgae from the Portuguese coast, molecular, and bioactivity assays were performed in 40 bacteria from several taxa. Two genes commonly associated with the production of bioactive compounds, nonribosomal peptide synthetases (NRPS), and polyketide synthases (PKS) genes were screened. Molecular analysis revealed that 95% of the planctomycetes potentially have one or both secondary bioactive genes; 85% amplified with PKS-I primers and 55% with NRPS primers. Some of the amplified genes were confirmed to be involved in secondary metabolite pathways. Using bioinformatic tools their biosynthetic pathways were predicted. The secondary metabolite genomic potential of strains LF1, UC8, and FC18 was assessed using in silico analysis of their genomes. Aqueous and organic extracts of the Planctomycetes were evaluated for their antimicrobial activity against an environmental Escherichia coli, E. coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923, Bacillus subtilis ATCC 6633, and a clinical isolate of Candida albicans. The screening assays showed a high number of planctomycetes with bioactive extracts revealing antifungal (43%) and antibacterial (54%) activity against C. albicans and B. subtilis, respectively. Bioactivity was observed in

  4. Planctomycetes as Novel Source of Bioactive Molecules

    Science.gov (United States)

    Graça, Ana P.; Calisto, Rita; Lage, Olga M.

    2016-01-01

    Marine environments are a fruitful source of bioactive compounds some of which are the newest leading drugs in medicinal therapeutics. Of particular importance are organisms like sponges and macroalgae and their associated microbiome. Planctomycetes, abundant in macroalgae biofilms, are promising producers of bioactive compounds since they share characteristics, like large genomes and complex life cycles, with the most bioactive bacteria, the Actinobacteria. Furthermore, genome mining revealed the presence of secondary metabolite pathway genes or clusters in 13 analyzed Planctomycetes genomes. In order to assess the antimicrobial production of a large and diverse collection of Planctomycetes isolated from macroalgae from the Portuguese coast, molecular, and bioactivity assays were performed in 40 bacteria from several taxa. Two genes commonly associated with the production of bioactive compounds, nonribosomal peptide synthetases (NRPS), and polyketide synthases (PKS) genes were screened. Molecular analysis revealed that 95% of the planctomycetes potentially have one or both secondary bioactive genes; 85% amplified with PKS-I primers and 55% with NRPS primers. Some of the amplified genes were confirmed to be involved in secondary metabolite pathways. Using bioinformatic tools their biosynthetic pathways were predicted. The secondary metabolite genomic potential of strains LF1, UC8, and FC18 was assessed using in silico analysis of their genomes. Aqueous and organic extracts of the Planctomycetes were evaluated for their antimicrobial activity against an environmental Escherichia coli, E. coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923, Bacillus subtilis ATCC 6633, and a clinical isolate of Candida albicans. The screening assays showed a high number of planctomycetes with bioactive extracts revealing antifungal (43%) and antibacterial (54%) activity against C. albicans and B. subtilis, respectively. Bioactivity was observed in

  5. Molecular Motion and Conformational Interconversion of Ir(I)·COD Included in Rebek's Self-Folding Octaamide Cavitand.

    Science.gov (United States)

    Korom, Saša; Martin, Eddy; Serapian, Stefano A; Bo, Carles; Ballester, Pablo

    2016-02-24

    We report experimental and theoretical evidence of restrained axial rotation for heteroleptic L2·Ir(I)·1,5-cyclooctadiene (COD) complexes included in the aromatic cavity of Rebek's self-folding octaamide cavitand. At 298 K, the axial spinning motion of the included organometallic guests was slow on the (1)H NMR time scale and produced a proton spectrum for the bound host indicative of C2 symmetry. Signals corresponding to aromatic protons of the bound host coalesced at 323 K, indicating that the spinning process of the included guest became fast on the (1)H NMR time scale and that the complex approached C4 symmetry. Surprisingly, lowering the temperature of the solution to 193 K induced an additional splitting of the proton signals observed at room temperature for both the bound host and the included guest. We propose the emergence of a new element of chirality in the complexes, which was associated with a slow interconversion, on the (1)H NMR time scale between the two chiral twisted-boat conformers of the chelated COD included in the already chiral cavity of the container. This leads to the inclusion complexes existing in solution as pairs of two racemic diastereomers. We estimated that the racemization barrier for the two cyclochiral conformers of the Ir(I) chelated COD was 5 kcal mol(-1) higher as an included organometallic complex than as free in solution. Furthermore, we performed a van't Hoff plot and determined that the inclusion of the organometallic complex in the cavitand was endothermic and exclusively driven by entropy (ΔH = 5.9 kcal mol(-1) and ΔS = 33.9 cal mol(-1) K(-1)). PMID:26812619

  6. Rubipodanin A, the First Natural N-Desmonomethyl Rubiaceae-Type Cyclopeptide from Rubia podantha, Indicating an Important Role of the N 9-Methyl Group in the Conformation and Bioactivity

    OpenAIRE

    Zhe Wang; Si-Meng Zhao; Li-Mei Zhao; Xiao-Qiang Chen; Guang-Zhi Zeng; Ning-Hua Tan

    2015-01-01

    One new cyclic hexapeptide named rubipodanin A (1), which is the first identified natural N-desmonomethyl Rubiaceae-type cyclopeptide, together with six known Rubiaceae-type cyclopeptides (2–7) were obtained using the TLC cyclopeptide protosite detection method with ninhydrin from the roots and rhizomes of Rubia podantha. The cyclopeptide structures were elucidated by extensive spectroscopic analysis, including 1D-NMR, 2D-NMR, IR, UV and MS. The solution conformation and biological activities...

  7. Workers’ Conformism

    Directory of Open Access Journals (Sweden)

    Nikolay Ivantchev

    2013-10-01

    Full Text Available Conformism was studied among 46 workers with different kinds of occupations by means of two modified scales measuring conformity by Santor, Messervey, and Kusumakar (2000 – scale for perceived peer pressure and scale for conformism in antisocial situations. The hypothesis of the study that workers’ conformism is expressed in a medium degree was confirmed partly. More than a half of the workers conform in a medium degree for taking risk, and for the use of alcohol and drugs, and for sexual relationships. More than a half of the respondents conform in a small degree for anti-social activities (like a theft. The workers were more inclined to conform for risk taking (10.9%, then – for the use of alcohol, drugs and for sexual relationships (8.7%, and in the lowest degree – for anti-social activities (6.5%. The workers who were inclined for the use of alcohol and drugs tended also to conform for anti-social activities.

  8. Characterization of the conformational space of a triple-stranded beta-sheet forming peptide with molecular dynamics simulations

    NARCIS (Netherlands)

    Soto, P; Colombo, G

    2004-01-01

    Molecular dynamics (MD) simulations have been performed on a series of mutants of the 20 amino acid peptide Betanova in order to critically assess the ability of MD simulations to reproduce the folding and stability of small beta-sheet-forming peptides on currently accessible timescales. Simulations

  9. Synthesis, Molecular and Crystal Structure Analysis of 1-(4-Methylbenzenesulfonylindole-3-carbaldehyde and DFT Investigation of Its Rotational Conformers

    Directory of Open Access Journals (Sweden)

    Julio Zukerman-Schpector

    2014-02-01

    Full Text Available Two independent molecules that differ in terms of rotation about the central S-N bond comprise the asymmetric unit of the title compound 1. The molecules have a V-shape with the dihedral angles between the fused ring system and benzene ring being 79.08(6° and 72.83(5°, respectively. The packing is mostly driven by p···p interactions occurring between the tolyl ring of one molecule and the C6 ring of the indole fused ring system of the other. DFT and IRC calculations for these and related 1-(arylsulfonylindole molecules showed that the rotational barrier about the S-N bond between conformers is within the 2.5–5.5 kcal/mol range. Crystal data for C16H13NO3S (1: Mr = 299.33, space group Pna21, a = 19.6152(4 Å, b = 11.2736(4 Å, c = 12.6334(3 Å, V = 2793.67(13 Å3, Z = 8, Z' = 2, R = 0.034.

  10. A conformational analysis of mouse Nalp3 domain structures by molecular dynamics simulations, and binding site analysis.

    Science.gov (United States)

    Sahoo, Bikash R; Maharana, Jitendra; Bhoi, Gopal K; Lenka, Santosh K; Patra, Mahesh C; Dikhit, Manas R; Dubey, Praveen K; Pradhan, Sukanta K; Behera, Bijay K

    2014-05-01

    Scrutinizing various nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) genes in higher eukaryotes is very important for understanding the intriguing mechanism of the host defense against pathogens. The nucleotide-binding domain (NACHT), leucine-rich repeat (LRR), and pyrin domains (PYD)-containing protein 3 (Nalp3), is an intracellular innate immune receptor and is associated with several immune system related disorders. Despite Nalp3's protective role during a pathogenic invasion, the molecular features and structural organization of this crucial protein is poorly understood. Using comparative modeling and molecular dynamics simulations, we have studied the structural architecture of Nalp3 domains, and characterized the dynamic and energetic parameters of adenosine triphosphate (ATP) binding in NACHT, and pathogen-derived ligands muramyl dipeptide (MDP) and imidazoquinoline with LRR domains. The results suggested that walker A, B and extended walker B motifs were the key ATP binding regions in NACHT that mediate self-oligomerization. The analysis of the binding sites of MDP and imidazoquinoline revealed LRR 7-9 to be the most energetically favored site for imidazoquinoline interaction. However, the binding free energy calculations using the Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) method indicated that MDP is incompatible for activating the Nalp3 molecule in its monomeric form, and suggest its complex interaction with NOD2 or other NLRs accounts for MDP recognition. The high binding affinity of ATP with NACHT was correlated to the experimental data for human NLRs. Our binding site prediction for imidazoquinoline in LRR warrants further investigation via in vivo models. This is the first study that provides ligand recognition in mouse Nalp3 and its spatial structural arrangements. PMID:24595807

  11. Conformal Infinity

    Directory of Open Access Journals (Sweden)

    Frauendiener Jörg

    2000-08-01

    Full Text Available The notion of conformal infinity has a long history within the research in Einstein's theory of gravity. Today, ``conformal infinity'' is related with almost all other branches of research in general relativity, from quantisation procedures to abstract mathematical issues to numerical applications. This review article attempts to show how this concept gradually and inevitably evolved out of physical issues, namely the need to understand gravitational radiation and isolated systems within the theory of gravitation and how it lends itself very naturally to solve radiation problems in numerical relativity. The fundamental concept of null-infinity is introduced. Friedrich's regular conformal field equations are presented and various initial value problems for them are discussed. Finally, it is shown that the conformal field equations provide a very powerful method within numerical relativity to study global problems such as gravitational wave propagation and detection.

  12. Conformal Infinity

    Directory of Open Access Journals (Sweden)

    Frauendiener Jörg

    2004-01-01

    Full Text Available The notion of conformal infinity has a long history within the research in Einstein's theory of gravity. Today, 'conformal infinity' is related to almost all other branches of research in general relativity, from quantisation procedures to abstract mathematical issues to numerical applications. This review article attempts to show how this concept gradually and inevitably evolved from physical issues, namely the need to understand gravitational radiation and isolated systems within the theory of gravitation, and how it lends itself very naturally to the solution of radiation problems in numerical relativity. The fundamental concept of null-infinity is introduced. Friedrich's regular conformal field equations are presented and various initial value problems for them are discussed. Finally, it is shown that the conformal field equations provide a very powerful method within numerical relativity to study global problems such as gravitational wave propagation and detection.

  13. Cyclic Zinc(II) Bisporphyrin-Based Molecular Switches: Supramolecular Control of Complexation-Mediated Conformational Switching and Photoinduced Electron Transfer.

    Science.gov (United States)

    Mondal, Pritam; Rath, Sankar Prasad

    2016-04-11

    A cyclic zinc(II) bisporphyrin with flexible linker was employed as a dynamic molecular switch under the regulation of π-acceptors (tetracyanoquinodimethane, trinitrofluorenone, 9-dicyanomethylenefluorene) and bidentate N-donor ligands (1,4-diazabicyclo[2.2.2]octane, pyrazine, 4,4'-bipyridine). The cyclic bisporphyrin host can efficiently encapsulate the π-acceptor guests through the strong π-π interaction, which can be replaced again by using a bidentate N-donor ligand, which coordinates strongly with the metal centers. The open conformation of the bisporphyrin can be efficiently recovered by removing the bidentate ligands using Cu(+) ion. During the process, two porphyrin rings also reversibly change their relative orientation between perpendicular and parallel. The behavior of the cyclic bisporphyrin was followed by using UV/Vis, (1) H NMR, fluorescence, and electrochemical analyses along with X-ray structure determination of the complexes. Moreover, control of photoinduced electron transfer (PET "ON-OFF") is also achieved by the use of guest exchange. Association constants for the host-guest binding were very high, which further explains the robust nature of such assemblies in solution. The experimental evidence is supported by DFT calculations. Such controllable dynamic features can constitute a new step towards "smart" adaptive molecular devices and the emergence of such systems is of significant interest in supramolecular chemistry. PMID:27062017

  14. Representation of target-bound drugs by computed conformers: implications for conformational libraries

    Directory of Open Access Journals (Sweden)

    Goede Andrean

    2006-06-01

    Full Text Available Abstract Background The increasing number of known protein structures provides valuable information about pharmaceutical targets. Drug binding sites are identifiable and suitable lead compounds can be proposed. The flexibility of ligands is a critical point for the selection of potential drugs. Since computed 3D structures of millions of compounds are available, the knowledge of their binding conformations would be a great benefit for the development of efficient screening methods. Results Integration of two public databases allowed superposition of conformers for 193 approved drugs with 5507 crystallised target-bound counterparts. The generation of 9600 drug conformers using an atomic force field was carried out to obtain an optimal coverage of the conformational space. Bioactive conformations are best described by a conformational ensemble: half of all drugs exhibit multiple active states, distributed over the entire range of the reachable energy and conformational space. A number of up to 100 conformers per drug enabled us to reproduce the bound states within a similarity threshold of 1.0 Å in 70% of all cases. This fraction rises to about 90% for smaller or average sized drugs. Conclusion Single drugs adopt multiple bioactive conformations if they interact with different target proteins. Due to the structural diversity of binding sites they adopt conformations that are distributed over a broad conformational space and wide energy range. Since the majority of drugs is well represented by a predefined low number of conformers (up to 100 this procedure is a valuable method to compare compounds by three-dimensional features or for fast similarity searches starting with pharmacophores. The underlying 9600 generated drug conformers are downloadable from the Super Drug Web site 1. All superpositions are visualised at the same source. Additional conformers (110,000 of 2400 classified WHO-drugs are also available.

  15. Conformational changes and slow dynamics through microsecond polarized atomistic molecular simulation of an integral Kv1.2 ion channel

    DEFF Research Database (Denmark)

    Bjelkmar, Pär; Niemelä, Perttu S; Vattulainen, Ilpo;

    2009-01-01

    Structure and dynamics of voltage-gated ion channels, in particular the motion of the S4 helix, is a highly interesting and hotly debated topic in current membrane protein research. It has critical implications for insertion and stabilization of membrane proteins as well as for finding how...... transitions occur in membrane proteins-not to mention numerous applications in drug design. Here, we present a full 1 micros atomic-detail molecular dynamics simulation of an integral Kv1.2 ion channel, comprising 120,000 atoms. By applying 0.052 V/nm of hyperpolarization, we observe structural rearrangements...... process. The coordinates of the transmembrane part of the simulated channel actually stay closer to the recently determined higher-resolution Kv1.2 chimera channel than the starting structure for the entire second half of the simulation (0.5-1 micros). Together with lipids binding in matching positions...

  16. A wrench in the works of human acetylcholinesterase: soman induced conformational changes revealed by molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Brian J Bennion

    Full Text Available Irreversible inactivation of human acetylcholinesterase (hAChE by organophosphorous pesticides (OPs and chemical weapon agents (CWA has severe morbidity and mortality consequences. We present data from quantum mechanics/molecular mechanics (QM/MM and 80 classical molecular dynamics (MD simulations of the apo and soman-adducted forms of hAChE to investigate the effects on the dynamics and protein structure when the catalytic Serine 203 is phosphonylated. We find that the soman phosphonylation of the active site Ser203 follows a water assisted addition-elimination mechanism with the elimination of the fluoride ion being the highest energy barrier at 6.5 kcal/mole. We observe soman-dependent changes in backbone and sidechain motions compared to the apo form of the protein. These alterations restrict the soman-adducted hAChE to a structural state that is primed for the soman adduct to be cleaved and removed from the active site. The altered motions and resulting structures provide alternative pathways into and out of the hAChE active site. In the soman-adducted protein both side and back door pathways are viable for soman adduct access. Correlation analysis of the apo and soman adducted MD trajectories shows that the correlation of gorge entrance and back door motion is disrupted when hAChE is adducted. This supports the hypothesis that substrate and product can use two different pathways as entry and exit sites in the apo form of the protein. These alternative pathways have important implications for the rational design of medical countermeasures.

  17. Understanding the Differences in Molecular Conformation of Carbohydrate and Protein in Endosperm Tissues of Grains with Different Biodegradation Kinetics Using Advanced Synchrotron Technology

    International Nuclear Information System (INIS)

    Conventional 'wet' chemical analyses rely heavily on the use of harsh chemicals and derivatization, thereby altering native seed structures leaving them unable to detect any original inherent structures within an intact tissue sample. A synchrotron is a giant particle accelerator that turns electrons into light (million times brighter than sunlight) which can be used to study the structure of materials at the molecular level. Synchrotron radiation-based Fourier transform IR microspectroscopy (SR-FTIRM) has been developed as a rapid, direct, non-destructive and bioanalytical technique. This technique, taking advantage of the brightness of synchrotron light and a small effective source size, is capable of exploring the molecular chemistry within the microstructures of a biological tissue without the destruction of inherent structures at ultraspatial resolutions within cellular dimensions. This is in contrast to traditional 'wet' chemical methods, which, during processing for analysis, often result in the destruction of the intrinsic structures of feeds. To date there has been very little application of this technique to the study of plant seed tissue in relation to nutrient utilization. The objective of this study was to use novel synchrotron radiation-based technology (SR-FTIRM) to identify the differences in the molecular chemistry and conformation of carbohydrate and protein in various plant seed endosperms within intact tissues at cellular and subcellular level from grains with different biodegradation kinetics. Barley grain (cv. Harrington) with a high rate (31.3%/h) and extent (78%), corn grain (cv. Pioneer) with a low rate (9.6%/h) and extent of (57%), and wheat grain (cv. AC Barrie) with an intermediate rate (23%/h) and extent (72%) of ruminal DM degradation were selected for evaluation. SR-FTIRM evaluations were performed at the National Synchrotron Light Source at the Brookhaven National Laboratory (Brookhaven, NY). These results suggest that SR-FTIRM plus

  18. Molecular structures and conformations of 1-benzenesulphonyl-2-oxo-5-alkoxypyrrolidines with anti-amnesic activity. X-ray, 1H-NMR and quantum mechanical (PM3) studies

    Science.gov (United States)

    Amato, Maria E.; Bandoli, Giuliano; Dolmella, Alessandro; Grassi, Antonio; Pappalardo, Giuseppe C.; Toja, Emilio

    1991-04-01

    The crystal and molecular structures of the nootropic agents RU-47001 ((±) 1-(4-nitrobenzenesulphonyl)-2-oxo-5-ethoxypyrrolidine) and RU-47064 ((±) 1-(4-nitrobenzenesulphonyl)-2-oxo-5-isopropyloxypyrrolidine) have been determined by X-ray analysis and their solution conformation has been investigated using 1H NMR spectroscopy. The conformations of these molecules together with those of their analogues RU-35929 ((±) 1-benzenesulphonyl-2-oxo-5-ethoxypyrrolidine), RU-47010 ((±) 1-(3-pyridinylsulphonyl)-2-oxo-5-ethoxypyrrolidine) and RU-35965 ((±) 1-benzenesulphonyl-2-oxo-5-isopropyloxypyrrolidine) have been deduced from semi-quantitative PM3 type theoretical calculations. The main feature of all compounds consists of a common envelope conformation with C (4) at the flap of the pyrrolidinone ring in the solid, that in solution changes into the analogous, but opposite, possible puckered conformational isomer. The 5-alkoxy groups were found rather flexible in solution. Theoretical preferred conformations about NS and SC bonds were in acceptable agreement with those of the solid state. The calculated torsional energetics suggested that 1- 5 do not undergo conformational interconversion.

  19. A Molecular Dynamics Investigation of Mycobacterium tuberculosis Prenyl Synthases: Conformational Flexibility and Implications for Computer-aided Drug Discovery.

    Science.gov (United States)

    Kim, Meekyum Olivia; Feng, Xinxin; Feixas, Ferran; Zhu, Wei; Lindert, Steffen; Bogue, Shannon; Sinko, William; de Oliveira, César; Rao, Guodong; Oldfield, Eric; McCammon, James Andrew

    2015-06-01

    With the rise in antibiotic resistance, there is interest in discovering new drugs active against new targets. Here, we investigate the dynamic structures of three isoprenoid synthases from Mycobacterium tuberculosis using molecular dynamics (MD) methods with a view to discovering new drug leads. Two of the enzymes, cis-farnesyl diphosphate synthase (cis-FPPS) and cis-decaprenyl diphosphate synthase (cis-DPPS), are involved in bacterial cell wall biosynthesis, while the third, tuberculosinyl adenosine synthase (Rv3378c), is involved in virulence factor formation. The MD results for these three enzymes were then compared with previous results on undecaprenyl diphosphate synthase (UPPS) by means of active site volume fluctuation and principal component analyses. In addition, an analysis of the binding of prenyl diphosphates to cis-FPPS, cis-DPPS, and UPPS utilizing the new MD results is reported. We also screened libraries of inhibitors against cis-DPPS, finding ~1 μm inhibitors, and used the receiver operating characteristic-area under the curve (ROC-AUC) method to test the predictive power of X-ray and MD-derived cis-DPPS receptors. We found that one compound with potent M. tuberculosis cell growth inhibition activity was an IC(50) ~0.5- to 20-μm inhibitor (depending on substrate) of cis-DPPS, a ~660-nm inhibitor of Rv3378c as well as a 4.8-μm inhibitor of cis-FPPS, opening up the possibility of multitarget inhibition involving both cell wall biosynthesis and virulence factor formation. PMID:25352216

  20. Conformational alterations induced by novel green 16-E2-16 gemini surfactant in xanthine oxidase: Biophysical insights from tensiometry, spectroscopy, microscopy and molecular modeling.

    Science.gov (United States)

    Akram, Mohd; Bhat, Imtiyaz Ahmad; Bhat, Waseem Feeroze; Kabir-ud-Din

    2015-11-01

    Herein we report the interaction of a biodegradable gemini surfactant, ethane-1,2-diyl bis(N,N-dimethyl-N-hexadecylammoniumacetoxy) dichloride (16-E2-16) with bovine milk xanthine oxidase (XO), employing tensiometry, fluorescence spectroscopy, UV spectroscopy, far-UV circular dichroism spectroscopy (CD), Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and computational molecular modeling. Surface tension results depict substantial changes in the micellar as well as interfacial parameters (CMC, ΠCMC, γCMC, Γmax, Amin, ΔGmic° and ΔGads°) of 16-E2-16 gemini surfactant upon XO combination, deciphering the interaction of XO with the gemini surfactant. Fluorescence measurements reveal that 16-E2-16 gemini surfactant causes quenching in the xanthine oxidase (XO) fluorescence spectra via static procedure and the values of various evaluated binding parameters (KSV, Kb, kq, ΔGb° and n) describe that 16-E2-16 effectively binds to XO. Three dimensional fluorescence, 8-anilino-1-naphthalene sulfonic acid (ANS) binding, F1F3 ratio, UV, CD, FTIR, SEM and TEM results delineate changes in the secondary structure of xanthine oxidase. Molecular docking results provide complement to the steady-state fluorescence findings and support the view that quenching occurs due to non-polar environment experienced by aromatic residues of the enzyme. The results of this study can help scientists to tune the conformation of an enzyme (XO) with biocompatible amphiphilic microstructures, which will help to unfold further understanding in the treatment modes of various diseases like gout, hyperuricemia, liver and brain necrosis. PMID:26057098

  1. Conformational flexibility of aspartame.

    Science.gov (United States)

    Toniolo, Claudio; Temussi, Pierandrea

    2016-05-01

    L-Aspartyl-L-phenylalanine methyl ester, better known as aspartame, is not only one of the most used artificial sweeteners, but also a very interesting molecule with respect to the correlation between molecular structure and taste. The extreme conformational flexibility of this dipeptide posed a huge difficulty when researchers tried to use it as a lead compound to design new sweeteners. In particular, it was difficult to take advantage of its molecular model as a mold to infer the shape of the, then unknown, active site of the sweet taste receptor. Here, we follow the story of the 3D structural aspects of aspartame from early conformational studies to recent docking into homology models of the receptor. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 376-384, 2016. PMID:27038223

  2. Facilitated receptor-recognition and enhanced bioactivity of bone morphogenetic protein-2 on magnesium-substituted hydroxyapatite surface

    Science.gov (United States)

    Huang, Baolin; Yuan, Yuan; Li, Tong; Ding, Sai; Zhang, Wenjing; Gu, Yuantong; Liu, Changsheng

    2016-04-01

    Biomaterial surface functionalized with bone morphogenetic protein-2 (BMP-2) is a promising approach to fabricating successful orthopedic implants/scaffolds. However, the bioactivity of BMP-2 on material surfaces is still far from satisfactory and the mechanism of related protein-surface interaction remains elusive. Based on the most widely used bone-implants/scaffolds material, hydroxyapatite (HAP), we developed a matrix of magnesium-substituted HAP (Mg-HAP, 2.2 at% substitution) to address these issues. Further, we investigated the adsorption dynamics, BMPRs-recruitment, and bioactivity of recombinant human BMP-2 (rhBMP-2) on the HAP and Mg-HAP surfaces. To elucidate the mechanism, molecular dynamic simulations were performed to calculate the preferred orientations, conformation changes, and cysteine-knot stabilities of adsorbed BMP-2 molecules. The results showed that rhBMP-2 on the Mg-HAP surface exhibited greater bioactivity, evidenced by more facilitated BMPRs-recognition and higher ALP activity than on the HAP surface. Moreover, molecular simulations indicated that BMP-2 favoured distinct side-on orientations on the HAP and Mg-HAP surfaces. Intriguingly, BMP-2 on the Mg-HAP surface largely preserved the active protein structure evidenced by more stable cysteine-knots than on the HAP surface. These findings explicitly clarify the mechanism of BMP-2-HAP/Mg-HAP interactions and highlight the promising application of Mg-HAP/BMP-2 matrixes in bone regeneration implants/scaffolds.

  3. Bioactive Hierarchical Structures for Genetic Control of Bone Morphogenesis

    Directory of Open Access Journals (Sweden)

    Pilar Sepulveda

    2002-09-01

    Full Text Available For thirty years it has been known that certain compositions of Na2O-CaO-P2O5-SiO 2 glasses will form a mechanically strong, chemical bond to bone. These materials have become known as bioactive glasses and the process of bonding is called bioactive fixation. Bioactive glasses are widely used clinically in the repair of bone defects. Recent research at the Imperial College Tissue Engineering Centre has now established that there is a genetic control of the cellular response to bioactive materials. Seven families of genes are up-regulated when primary human osteoblasts are exposed to the ionic dissolution products of bioactive glasses. The gene expression occurs very rapidly, within two days, and includes enhanced expression of cell cycle regulators. The consequence is rapid differentiation of the osteoblasts into a mature phenotype and formation of large three-dimensional bone nodules within six days in vitro. These cell culture results correlate with extensive human clinical results using the same bioactive material. The new genetic theory of bioactive materials provides a scientific foundation for molecular design of new generation of resorbable bioactive materials for tissue engineering and in situ tissue regeneration and repair. Application of this theory to the synthesis of bioactive foams for tissue engineering of bone is described.

  4. A carbon-13 NMR spin-lattice relaxation study of the molecular conformation of the nootropic drug 2-oxopyrrolidin-1-ylacetamide

    Science.gov (United States)

    Baldo, M.; Grassi, A.; Guidoni, L.; Nicolini, M.; Pappalardo, G. C.; Viti, V.

    The spin-lattice relaxation times ( T1) of carbon-13 resonances of the drug 2-oxopyrrolidin- 1-ylacetamide ( 2OPYAC) were determined in CDCl 3 + DMSO and H 2O solutions to investigate the internal conformational flexibility. The measured T1s for the hydrogen-bearing carbon atoms of the 2-pyrrolidone ring fragment were diagnostic of a rigid conformation with respect to the acetamide linked moiety. The model of anisotropic reorientation of a rigid body was used to analyse the measured relaxation data in terms of a single conformation. Owing to the small number of T1 data available the fitting procedure for each of the possible conformations failed. The structure corresponding to the rigid conformation was therefore considered to be the one that is strongly stabilized by internal hydrogen bonding as predicted on the basis of theoretical MO ab initio quantum chemical calculations.

  5. Conformation Distributions in Adsorbed Proteins.

    Science.gov (United States)

    Meuse, Curtis W.; Hubbard, Joseph B.; Vrettos, John S.; Smith, Jackson R.; Cicerone, Marcus T.

    2007-03-01

    While the structural basis of protein function is well understood in the biopharmaceutical and biotechnology industries, few methods for the characterization and comparison of protein conformation distributions are available. New methods capable of measuring the stability of protein conformations and the integrity of protein-protein, protein-ligand and protein-surface interactions both in solution and on surfaces are needed to help the development of protein-based products. We are developing infrared spectroscopy methods for the characterization and comparison of molecular conformation distributions in monolayers and in solutions. We have extracted an order parameter describing the orientational and conformational variations of protein functional groups around the average molecular values from a single polarized spectrum. We will discuss the development of these methods and compare them to amide hydrogen/deuterium exchange methods for albumin in solution and on different polymer surfaces to show that our order parameter is related to protein stability.

  6. The molecular structure, conformation, potential to internal rotation and force field of 2,2,2-trifluoroacetamide as studied by gas electron diffraction and quantum chemical calculations

    Science.gov (United States)

    Gundersen, Snefrid; Samdal, Svein; Seip, Ragnhild; Shorokhov, Dmitry J.; Strand, Tor G.

    1998-04-01

    2,2,2-Trifluoroacetamide (TFA) has been studied by electron diffraction (ED), ab initio Hartree-Fock (HF), density functional theory (DFT), and MP2 calculations. The calculations give one conformation with one of the CF bonds anti to the CO bond and a planar NH 2 group, except for MP2/6-311 + + G∗∗, which predicts a slightly pyramidale NH 2 group. A molecular force field has been determined, and the fundamental frequencies have tentatively been assigned. The refined structural parameters were determined using constrained ED, i.e. ab initio results are included as constraints in the analysis. The structural parameters are: rg(N-H 4) = 1.040(4), rg(CO) = 1.211(2), rg(C-N) = 1.362(4), rg = 1.562(1), rg(C-F 7) = 1.347(1), ∠ αOCN = 126.5(2), ∠ αCCN = 116.3(4), ∠ αCCF 7 = 111.9(1), and ∠ αCNH 4 = 118.5(11). Bond distances are in Å and bond angles in degrees. Uncertainties are one standard deviation from least squares refinement using a diagonal weight matrix and inclusion of the uncertainty in the electron wavelength. The structural parameters have been compared with related amides. The Fourier coefficients V3 and V6 in the potential to internal rotation of the CF 3 group, V(α) = 1/2∗V 3∗(1 - cos(3∗α)) + 1/2∗V 6∗(1 - cos(6∗α)) , are determined to be 2.7(4) and - 0.7(3) kJ/mol, respectively. The syn barrier is experimentally determined to be 2.6(4) kJ/mol, which is in good agreeent with theoretical calculations.

  7. DFT Studies of the Molecular Structures and Conformational Processes of 1,2-, 1,3- and 1,4-Dithiepane

    Institute of Scientific and Technical Information of China (English)

    HAGHDADI Mina; HAMZEHLUIYAN Mahshid

    2008-01-01

    In this study density functional theory (DFT) calculations at B3LYP/6-31G(d), B3LYP/6-31+G(d) and B3LYP/6-311+G(2df,2p) levels for geometry optimization and total energy calculation were applied for investigation of the important energy-minimum conformations and transition-state of 1,2-, 1,3-, and 1,4-dithiepanes. Moreover, ab initio calculations at HF/6-31G(d) level of theory for geometry optimization and MP2/6-311G(d)//HF/6-31G(d) level for a single-point total energy calculation were reported for different conformers. The obtained resuits reveal that, the twist-chair conformer is a global minimum for all of these compounds. Also, two local minimum were found in each case, which are twisted-chair and twisted-boat conformers. The boat and chair geometries are transition states. The minimum energy conformation of 1,2-dithiepane is more stable than the lowest energyforms of 1,3-dithiepane and 1,4-dithiepane. Furthermore, the anomeric effect was investigated for 1,3-dithiepane by the natural bond orbital method. The computational results of this study shows that all conformers of 1,3-dithiepane have a hypercojugation system. Finally, the 13C NMR chemical shifts for the conformers of 1,4-dithiepane were calculated, which have good correlation with their experimental values.

  8. SISTEMA DE GESTIÓN DE NO CONFORMIDADES PARA LOS PRODUCTOS COMERCIALES DEL CENTRO DE INMUNOLOGÍA MOLECULAR / NON-CONFORMITIES MANAGEMENT SYSTEM FOR COMMERCIAL PRODUCTS IN THE MOLECULAR IMMUNOLOGY CENTER

    Directory of Open Access Journals (Sweden)

    Yuliet Romero-Ruiz

    2011-03-01

    Full Text Available

    Este artículo describe el diseño y la implementación de un sistema de gestión para las no conformidades generadas durante la fabricación y la distribución de los productos biotecnológicos comerciales en el Centro de Inmunología Molecular. El trabajo abarcó desde la etapa de planificación, con el establecimiento de los indicadores de eficiencia y eficacia del sistema, hasta la evaluación del mismo. Para el control del sistema se emplearon técnicas de ingeniería de la calidad. El diseño del sistema se basó en los principios de la gestión por procesos, la administración del riesgo y el enfoque de sistema. Al año de implementación del sistema se habían gestionado 129 no conformidades y el 83% de ellas estaban cerradas. Además, se observó una disminución en el número de las no conformidades detectadas por las inspecciones regulatorias.

    Abstract

    This article describes the design and implementation of a management system for nonconformities generated during the manufacture and distribution of commercial biotechnological products in the Molecular Immunology Centre. The work ranged from the planning stage, with the establishment of indicators of efficiency and effectiveness of the system, to its assessment. Quality engineering techniques were used for monitoring the system. The system design was based on the principles of process management, risk management and systems approach. One year after the implementation of the system, 129 non-conformities had been managed and 83% of them were closed. In addition, there was a decrease in the number of nonconformities identified by regulatory inspections.

  9. Frog: a FRee Online druG 3D conformation generator.

    Science.gov (United States)

    Leite, T Bohme; Gomes, D; Miteva, M A; Chomilier, J; Villoutreix, B O; Tufféry, P

    2007-07-01

    In silico screening methods based on the 3D structures of the ligands or of the proteins have become an essential tool to facilitate the drug discovery process. To achieve such process, the 3D structures of the small chemical compounds have to be generated. In addition, for ligand-based screening computations or hierarchical structure-based screening projects involving a rigid-body docking step, it is necessary to generate multi-conformer 3D models for each input ligand to increase the efficiency of the search. However, most academic or commercial compound collections are delivered in 1D SMILES (simplified molecular input line entry system) format or in 2D SDF (structure data file), highlighting the need for free 1D/2D to 3D structure generators. Frog is an on-line service aimed at generating 3D conformations for drug-like compounds starting from their 1D or 2D descriptions. Given the atomic constitution of the molecules and connectivity information, Frog can identify the different unambiguous isomers corresponding to each compound, and generate single or multiple low-to-medium energy 3D conformations, using an assembly process that does not presently consider ring flexibility. Tests show that Frog is able to generate bioactive conformations close to those observed in crystallographic complexes. Frog can be accessed at http://bioserv.rpbs.jussieu.fr/Frog.html. PMID:17485475

  10. Rescuing compound bioactivity in a secondary cell-based screening by using γ-cyclodextrin as a molecular carrier

    Directory of Open Access Journals (Sweden)

    Claveria-Gimeno R

    2015-03-01

    Full Text Available Rafael Claveria-Gimeno,1–3 Sonia Vega,3 Valeria Grazu,4 Jesús M de la Fuente,4–6 Angel Lanas,2,8–10 Adrian Velazquez-Campoy,2,3,7 Olga Abian1–3,8 1Instituto Aragonés de Ciencias de la Salud (IACS, Zaragoza, Spain; 2IIS Aragón, Zaragoza, Spain; 3Institute of Biocomputation and Physics of Complex Systems (BIFI, Joint Unit IQFR-CSIC-BIFI, Universidad de Zaragoza, Zaragoza, Spain; 4Instituto de Nanociencia de Aragon (INA, Universidad de Zaragoza, Zaragoza, Spain; 5Instituto de Ciencia de Materiales de Aragón (ICMA, CSIC-Universidad de Zaragoza, Zaragoza, Spain; 6Institute NanoBiomedicine and Engineering, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 7Fundacion ARAID, Government of Aragon, Spain; 8Centro de Investigación Biomédica en Red en el Área Temática de Enfermedades Hepáticas y Digestivas (CIBERehd, Barcelona, Spain; 9Servicio de Aparato Digestivo, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain; 10Department of Medicine, University of Zaragoza, Zaragoza, Spain Abstract: In vitro primary screening for identifying bioactive compounds (inhibitors, activators or pharmacological chaperones against a protein target results in the discovery of lead compounds that must be tested in cell-based efficacy secondary screenings. Very often lead compounds do not succeed because of an apparent low potency in cell assays, despite an excellent performance in primary screening. Primary and secondary screenings differ significantly according to the conditions and challenges the compounds must overcome in order to interact with their intended target. Cellular internalization and intracellular metabolism are some of the difficulties the compounds must confront and different strategies can be envisaged for minimizing that problem. Using a novel screening procedure we have identified 15 compounds inhibiting the hepatitis C NS3 protease in an allosteric fashion. After characterizing biophysically the interaction

  11. Design, synthesis and bioactivity of novel ALS enzyme inhibitors (II)——Molecular mechanics, quantum chemistry and structure-activity relationship studies on the herbicidal heterocyclic sulfonamide

    Institute of Scientific and Technical Information of China (English)

    陆荣健; 杨华铮; 尚贞锋; 汪惟为; 潘荫明; 赵学庄

    1996-01-01

    In view of quantum pharmacology, the structure-activity relationships of different kinds of fused heterocydic sulfonamides with the same mode of action were first investigated using molecular mechanics, quantum chemistry and discriminatory analysis. It has been found that the process of the interaction of the fused heterocydic sulfonamide with ALS enzyme involves the electropositive region of the sulfonyl bridge chain and the electronegative region of the heterocydic moiety. The herbicidal activity is related to the potency of electric charge translocation of the related regions.

  12. The tubulin-bound conformation of paclitaxel: T-taxol vs "PTX-NY".

    Science.gov (United States)

    Yang, Yutao; Alcaraz, Ana A; Snyder, James P

    2009-03-27

    Nearly 35 years after its discovery and 11 years after FDA approval of paclitaxel (PTX) as a breakthrough anticancer drug, the 3-D structure of the agent bound to its beta-tubulin target was proposed to be T-Taxol. The latter bioactive form has recently been challenged by the Ojima group with a structure, "PTX-NY" ("REDOR Taxol"), in which the C-13 side chain is proposed to adopt a different conformation and an alternative hydrogen-bonding pattern in the tubulin binding site. Previously, the two conformers were compared to show that only T-Taxol fits the PTX-derived electron crystallographic density. That work has been extended by molecular mechanics and quantum chemical methods to reveal that the PTX-NY conformation is relatively less stable, on average, by 10-11 kcal/mol. In agreement with NMR studies, an 11 ns molecular dynamics treatment for PTX in an explicit water pool locates T-Taxol along the trajectory, but not PTX-NY. Docking of various PTX conformers into the electron crystallographic binding site of tubulin demonstrates that PTX-NY cannot be accommodated unless the pocket is reorganized in violation of the experimental constraints. Finally, analysis of the structures of T-Taxol and PTX-NY for their capacity to predict the existence of superpotent PTX analogues discloses that only the former forecasts such analogues, as now established by the T-Taxol-inspired synthesis of bridged taxanes. In sum, all empirical criteria support T-Taxol as the bound conformation of PTX on beta-tubulin in microtubules.

  13. Non-conformable, partial and conformable transposition

    DEFF Research Database (Denmark)

    König, Thomas; Mäder, Lars Kai

    2013-01-01

    Although member states are obliged to transpose directives into domestic law in a conformable manner and receive considerable time for their transposition activities, we identify three levels of transposition outcomes for EU directives: conformable, partially conformable and non-conformable...... and the Commission regarding a directive’s outcome, play a much more strategic role than has to date acknowledged in the transposition literature. Whereas disagreement of a member state delays conformable transposition, it speeds up non-conformable transposition. Disagreement of the Commission only prolongs...

  14. Multiple conformations of proteins in native state

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Examples of protein sequences that can adopt multiple native states are recently accumulated. Characterization of the protein multiple conformations will have important implications for our understanding of the relationship between structure and function, and their folding kinetics. In present review, the experimental evidence for the existence of multiple conformations in the native state of proteins, the molecular basis and the biological significance of multiple conformations of proteins are focused.

  15. Molecular modeling studies and in vitro bioactivity evaluation of a set of novel 5-nitro-heterocyclic derivatives as anti-T. cruzi agents.

    Science.gov (United States)

    Paula, Fávero Reisdorfer; Jorge, Salomão Dória; de Almeida, Leonardo Viana; Pasqualoto, Kerly Fernanda Mesquita; Tavares, Leoberto Costa

    2009-04-01

    In this study, in vitro anti-T. cruzi activity assays of nifuroxazide (NX) analogues, such as 5-nitro-2-furfuryliden and 5-nitro-2-theniliden derivatives, were performed. A molecular modeling approach was also carried out to relate the lipophilicity potential (LP) property and biological activity data. The majority of the NX derivatives showed increased anti-T. cruzi activity in comparison to the reference drug, benznidazole (BZN). Additionally, the 5-nitro-2-furfuryliden derivatives presented better pharmacological profile than the 5-nitro-2-theniliden analogues. The LP maps and corresponding ClogP values indicate that there is an optimum lipophilicity value, which must be observed in the design of new potential anti-T. cruzi agents. PMID:19303308

  16. A Study of Bioactivity of Corn Peptides with Low Molecular Weight Ⅱ: Effect on Plasma Free Amino Acid Concentrations in Rats

    Institute of Scientific and Technical Information of China (English)

    XU Li; ZHANG Li-qiang; WU Xiao-xia; WANG Na; ZHANG Xue-zhong

    2003-01-01

    The effects of the ingestion of corn peptides with a low molecular weight(LMCP) prepared from zein on some plasma free amino acid concentrations in rats that had taken ethanol were investigated. LMCP(1.0 g/kg body weight) in 15% ethanol(10 mL/kg body weight) was given to Wister rats by intragastrical administration. The amino acid analysis showed that the concentrations of alanine, leucine, and proline in the plasma reached their maximum levels at 30 min for the LMCP-intake group. They are 582.39, 99.60 and 272.51 μg/L, respectively. But in the control group, the plasma free amino acid levels were not changed obviously. Therefore, LMCP could cause an increase in concentration of some free amino acids such as alanine, leucine and proline etc. in plasma of the rats that have taken ethanol.

  17. Antibacterial action mode of quaternized carboxymethyl chitosan/poly(amidoamine) dendrimer core–shell nanoparticles against Escherichia coli correlated with molecular chain conformation

    Energy Technology Data Exchange (ETDEWEB)

    Wen, Yan [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); School of Science, Tianjin University of Commerce, Tianjin 300134 (China); Yao, Fanglian, E-mail: yaofanglian@tju.edu.cn [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Sun, Fang [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Tan, Zhilei [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300222 (China); Tian, Liang [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); Xie, Lei; Song, Qingchao [College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300222 (China)

    2015-03-01

    The action mode of quaternized carboxymethyl chitosan/poly(amidoamine) dendrimer core–shell nanoparticles (CM-HTCC/PAMAM) against Escherichia coli (E. coli) was investigated via a combination of approaches including measurements of cell membrane integrity, outer membrane (OM) and inner membrane (IM) permeability, and scanning electron microscopy (SEM). CM-HTCC/PAMAM dendrimer nanoparticles likely acted in a sequent event-driven mechanism, beginning with the binding of positively charged groups from nanoparticle surface with negative cell surface, thereby causing the disorganization of cell membrane, and subsequent leakage of intracellular components which might ultimately lead to cell death. Moreover, the chain conformation of polymers was taken into account for a better understanding of the antibacterial action mode by means of viscosity and GPC measurements. High utilization ratio of positive charge and large specific surface area generated from a compacted conformation of CM-HTCC/PAMAM, significantly different from the extended conformation of HTCC, were proposed to be involved in the antibacterial action. - Highlights: • The nanoparticles exerted antibacterial activity in a sequent event-driven manner. • Electrostatic interaction and surface adsorption shared roles in antibacterial mode. • The two factors were controlled by the compacted conformation of nanoparticles.

  18. Conformal transformations and conformal invariance in gravitation

    CERN Document Server

    Dabrowski, Mariusz P; Blaschke, David B

    2008-01-01

    Conformal transformations are frequently used tools in order to study relations between various theories of gravity and Einstein relativity. Because of that, in this paper we discuss the rules of conformal transformations for geometric quantities in general relativity. In particular, we discuss the conformal transformations of the matter energy-momentum tensor. We thoroughly discuss the latter and show the subtlety of the conservation law (i.e., the geometrical Bianchi identity) imposed in one of the conformal frames in reference to the other. The subtlety refers to the fact that conformal transformation ``creates'' an extra matter term composed of the conformal factor which enters the conservation law. In an extreme case of the flat original spacetime the matter is ``created'' due to work done by the conformal transformation to bend the spacetime which was originally flat. We also discuss how to construct the conformally invariant gravity which, in the simplest version, is a special case of the Brans-Dicke t...

  19. Exploring the conformational energy landscape of glassy disaccharides by cross polarization magic angle spinning 13C nuclear magnetic resonance and numerical simulations. II. Enhanced molecular flexibility in amorphous trehalose

    Science.gov (United States)

    Lefort, Ronan; Bordat, Patrice; Cesaro, Attilio; Descamps, Marc

    2007-01-01

    This paper uses chemical shift surfaces to simulate experimental C13 cross polarization magic angle spinning spectra for amorphous solid state disaccharides, paying particular attention to the glycosidic linkage atoms in trehalose, sucrose, and lactose. The combination of molecular mechanics with density functional theory/gauge invariant atomic orbital ab initio methods provides reliable structural information on the conformational distribution in the glass. The results are interpreted in terms of an enhanced flexibility that trehalose possesses in the amorphous solid state, at least on the time scale of C13 nuclear magnetic resonance measurements. Implications of these findings for the fragility of trehalose glass and bioprotectant action are discussed.

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

    Science.gov (United States)

    Dhanaraj, C Justin; Johnson, Jijo

    2015-10-01

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

  1. A Study on Bioactivity of Corn Peptides with Low Molecular Weight(Ⅰ) --Effect of an Intake of them on Alcohol Metabolism in Rats

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    This study aims at the effects of an intake of low molecular weight corn peptides(LMCPs) prepared from zein on alcohol metablism in rats. LMCPs(1.0 g/kg body weight) in 15% ethanol(10 mL/kg body weight) were given to Wister rats by intragastric gavage. The assay of blood ethanol was conducted by using the enzyme-based assay kit. The amino acid analysis was made with an amino acid analyzer. The data of the animal experiments showed that LMCPs could accelerate the metabolism of alcohol in rats. In the control group, the blood ethanol concentration reached the maximum level of (827.0±77.3) mg/L after ethanol loading for 30 min, then gradually decreased. In contrast, the blood ethanol concentration only reached (527.25±47.0) mg/L after 30 min in the group of LMCPs taken. These results indicate that LMCPs could decrease ethanol concentration in blood rapidly.

  2. A Study on bioactivity of Corn Peptides with Low Molecular Weight(Ⅰ)——Effect of an Intake of them on Alcohol Metabolism in Rats

    Institute of Scientific and Technical Information of China (English)

    XULi; FEIXiao-fang; ZHANGLi-qiang; ZHANGXue-zhong

    2003-01-01

    This study aims at the effects of an intake of low molecular weight corn peptides(LMCP5)prepared from zein on alcohol mentablism in rats.LMCPs(1.0g/kg dody weight)in 15% ethanol(10mL/kg body weight) were given to Wister rats by intragastric gavage.The assay of blood ethanol was conducted by using the enzyme-based assay kit.The amino acid analysis was made with an amino acid analyzer.The data of the animal experiments showed that LMCPs could accelerate the metabolism of alcohol in rats.In the control group,the blood ethanol concentration reached the maximun level of (827.0±77.3)mg/L after ethanol loading for 30min,then gradually decreased.In contrast,the blood ethanol concentration only reached (527.25±47.0)mg/L after 30 min in the group of LMCPs taken.These results indicate that LMCPs could decrease ethanol concentration in blood rapidly.

  3. Conformal isoparametric hypersurfaces with two distinct conformal principal curvatures in conformal space

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The conformal geometry of regular hypersurfaces in the conformal space is studied.We classify all the conformal isoparametric hypersurfaces with two distinct conformal principal curvatures in the conformal space up to conformal equivalence.

  4. Applied bioactive polymeric materials

    CERN Document Server

    Carraher, Charles; Foster, Van

    1988-01-01

    The biological and biomedical applications of polymeric materials have increased greatly in the past few years. This book will detail some, but not all, of these recent developments. There would not be enough space in this book to cover, even lightly, all of the major advances that have occurred. Some earlier books and summaries are available by two of this book's Editors (Gebelein & Carraher) and these should be consul ted for additional information. The books are: "Bioactive Polymeric Systems" (Plenum, 1985); "Polymeric Materials In Medication" (Plenum, 1985); "Biological Acti vi ties of Polymers" (American Chemical Society, 1982). Of these three, "Bioacti ve Polymeric Systems" should be the most useful to a person who is new to this field because it only contains review articles written at an introductory level. The present book primarily consists of recent research results and applications, with only a few review or summary articles. Bioactive polymeric materials have existed from the creation of life...

  5. Bioactive phytochemicals in flaxseed

    OpenAIRE

    Johnsson, Pernilla

    2009-01-01

    Flaxseed (Linum usitatissimum L.) is rich in health-promoting bioactive compounds. Among plant foods, flaxseed has the highest content of lignans, mainly in the form of secoisolariciresinol diglucoside (SDG). Flaxseed oil also has a very high concentration of the essential omega-3 fatty acid alpha-linolenic acid (ALA). This thesis presents studies on both SDG and ALA. An HPLC method for quantification of SDG in hydrolysed flaxseed extracts was developed and used to compare the SDG content in ...

  6. Conformational properties of oxazoline-amino acids

    Science.gov (United States)

    Staś, Monika; Broda, Małgorzata A.; Siodłak, Dawid

    2016-04-01

    Oxazoline-amino acids (Xaa-Ozn) occur in natural peptides of potentially important bioactivity. The conformations of the model compounds: Ac-(S)-Ala-Ozn(4R-Me), Ac-(S)-Ala-Ozn(4S-Me), and (gauche+, gauche-, anti) Ac-(S)-Val-Ozn(4R-Me) were studied at meta-hybrid M06-2X/6-311++G(d,p) method including solvent effect. Boc-L-Ala-L-Ozn-4-COOMe and Boc-L-Val-L-Ozn-4-COOMe were synthesized and studied by FT-IR and NMR-NOE methods. The conformations in crystal state were gathered from the Cambridge Structural Data Base. The main conformational feature of the oxazoline amino acids is the conformation β2 (ϕ,ψ ∼ -161°, -6°), which predominates in weakly polar environment and still is accessible in polar surrounding. The changes of the conformational preferences towards the conformations αR (ϕ,ψ ∼ -70°, -15°) and then β (ϕ,ψ ∼ -57°, -155°) are observed with increase of the environment polarity.

  7. Structural studies on a non toxic homologue of type II RIPs from bitter gourd: Molecular basis of non toxicity, conformational selection and glycan structure

    Indian Academy of Sciences (India)

    Thyageshwar Chandran; Alok Sharma; M Vijayan

    2015-12-01

    The structures of nine independent crystals of bitter gourd seed lectin (BGSL), a non-toxic homologue of type II RIPS, and its sugar complexes have been determined. The four-chain, two-fold symmetric, protein is made up of two identical two-chain modules, each consisting of a catalytic chain and a lectin chain, connected by a disulphide bridge. The lectin chain is made up of two domains. Each domain carries a carbohydrate binding site in type II RIPS of known structure. BGSL has a sugar binding site only on one domain, thus impairing its interaction at the cell surface. The adenine binding site in the catalytic chain is defective. Thus, defects in sugar binding as well as adenine binding appear to contribute to the non-toxicity of the lectin. The plasticity of the molecule is mainly caused by the presence of two possible well defined conformations of a surface loop in the lectin chain. One of them is chosen in the sugar complexes, in a case of conformational selection, as the chosen conformation facilitates an additional interaction with the sugar, involving an arginyl residue in the loop. The -glycosylation of the lectin involves a plant-specific glycan while that in toxic type H RIPS of known structure involves a glycan which is animal as well as plant specific.

  8. Molecular Dynamics Characterization of the Conformational Landscape of Small Peptides: A Series of Hands-On Collaborative Practical Sessions for Undergraduate Students

    Science.gov (United States)

    Rodrigues, João P. G. L. M.; Melquiond, Adrien S. J.; Bonvin, Alexandre M. J. J.

    2016-01-01

    Molecular modelling and simulations are nowadays an integral part of research in areas ranging from physics to chemistry to structural biology, as well as pharmaceutical drug design. This popularity is due to the development of high-performance hardware and of accurate and efficient molecular mechanics algorithms by the scientific community. These…

  9. Conformal transformations and conformal invariance in gravitation

    OpenAIRE

    Dabrowski, Mariusz P.; Garecki, Janusz; Blaschke, David B.

    2008-01-01

    Conformal transformations are frequently used tools in order to study relations between various theories of gravity and the Einstein relativity. In this paper we discuss the rules of these transformations for geometric quantities as well as for the matter energy-momentum tensor. We show the subtlety of the matter energy-momentum conservation law which refers to the fact that the conformal transformation "creates" an extra matter term composed of the conformal factor which enters the conservat...

  10. Conformational Analysis of Seven Membered Nitrogen Heterocycles Employing Molecular Modeling. Part II: 1-(ONitrophenyl)-2-Phenyl-1h-4,5,6,7-Tetrahydro-1,3-Diazepine

    OpenAIRE

    Hedrera, Mónica E.; Robinsohn, Adriana; Perillo, Isabel A.

    2000-01-01

    Geometry optimization of 1-(o-nitrophenyl)-2-phenyl-1H-4,5,6,7-tetrahydro-1,3-diazepine is performed by means of molecular modeling. Results are correlated with theoretical and experimental UV spectra.

  11. Conformational Analysis of Seven Membered Nitrogen Heterocycles Employing Molecular Modeling. Part II: 1-(ONitrophenyl-2-Phenyl-1h-4,5,6,7-Tetrahydro-1,3-Diazepine

    Directory of Open Access Journals (Sweden)

    Mónica E. Hedrera

    2000-03-01

    Full Text Available Geometry optimization of 1-(o-nitrophenyl-2-phenyl-1H-4,5,6,7-tetrahydro-1,3-diazepine is performed by means of molecular modeling. Results are correlated with theoretical and experimental UV spectra.

  12. Bridging converts a noncytotoxic nor-paclitaxel derivative to a cytotoxic analogue by constraining it to the T-Taxol conformation.

    Science.gov (United States)

    Tang, Shoubin; Yang, Chao; Brodie, Peggy; Bane, Susan; Ravindra, Rudravajhala; Sharma, Shubhada; Jiang, Yi; Snyder, James P; Kingston, David G I

    2006-08-31

    The synthesis of the bridged A-nor-paclitaxel 4 has been achieved from paclitaxel in a key test of the T-Taxol conformational hypothesis. Although the unbridged A-nor-paclitaxel 3 is essentially noncytotoxic, the bridged analogue 4 is strongly cytotoxic. This result provides strong evidence for the T-Taxol conformation as the bioactive tubulin-binding conformation of paclitaxel.

  13. Molecular recognition studies on supramolecular systems (XXIV)——Conformations and complexation abilities of chemically modified cyclodextrins in aqueous solution

    Institute of Scientific and Technical Information of China (English)

    刘育; 尤长城

    2000-01-01

    Circular dichroism spectral and fluorescence decay methods have been employed to determine the conformations of mono[6-(p-tolylseleno)-6-deoxy]-p-CD(1), mono(6-anilino-6-deoxy) β -CD (2) and mono[6-(L-tryptophan)-6-deoxy]-β-CD (3) in phosphate buffer solution (pH 7.2, 0.1 mol dm-3) at 298.15 K. The results indicate that compounds 2 and 3 formed self-inclusion complexes in aqueous buffer solution, while the substituent of compound 1 was not included into cyclodextrin cavity at all. Furthermore, the complex stability constant (logKs) and Gibbs free energy change (-ΔG° ) of these three cylcodextrin derivatives with several cycloalkanols have been determined by circular dichroism spectral titration in phosphate buffer solution at 298.15 K. It is found that the location of the substituent affects the stability of host-guest complex in aqueous solution.

  14. Synthesis, Structure, and Molecular Recognition of S6 - and (SO2 )6 -Corona[6](het)arenes: Control of Macrocyclic Conformation and Properties by the Oxidation State of the Bridging Heteroatoms.

    Science.gov (United States)

    Guo, Qing-Hui; Zhao, Liang; Wang, Mei-Xiang

    2016-05-10

    We report herein the synthesis, structure, and molecular recognition of S6 - and (SO2 )6 -corona[6](het)arenes, and demonstrate a unique and efficient strategy of regulating macrocyclic conformation and properties by adjusting the oxidation state of the heteroatom linkages. The one-pot nucleophilic aromatic substitution reaction of 1,4-benzenedithiol derivatives, biphenyl-4,4'-dithiol and 9,9-dipropyl-9H-fluorene-2,7-dithiol with 3,6-dichlorotetrazine afforded S6 -corona[3]arene[3]tetrazines. These compounds underwent inverse-electron-demand Diels-Alder reaction with enamines and norbornadiene to produce S6 -corona[3]arene[3]pyridazines. Facile oxidation of sulfide linkages yielded (SO2 )6 -corona[3]arene[3]pyridazines. All corona[6](het)arenes adopted generally hexagonal macrocyclic ring structures; however, their electronic properties and conformation could be fine-tuned by altering the oxidation state of the sulfur linkages. Whereas (SO2 )6 -corona[3]arene[3]pyridazines were electron-deficient, S6 -corona[3]arene[3]pyridazines acted as electron-rich macrocyclic hosts that recognized various organic cations in both aqueous and organic solutions.

  15. Case studies of the synthesis of bioactive cyclodepsipeptide natural products

    OpenAIRE

    Markus Kaiser; Stolze, Sara C.

    2013-01-01

    Cyclodepsipeptide natural products often display intriguing biological activities that along with their complex molecular scaffolds, makes them interesting targets for chemical synthesis. Although cyclodepsipeptides feature highly diverse chemical structures, their synthesis is often associated with similar synthetic challenges such as the establishment of a suitable macrocyclization methodology. This review therefore compiles case studies of synthetic approaches to different bioactive cyclod...

  16. Bioactive molecules from sea hares.

    Science.gov (United States)

    Kamiya, H; Sakai, R; Jimbo, M

    2006-01-01

    Sea hares, belonging to the order Opisthobranchia, subclass Gastropoda, are mollusks that have attracted many researchers who are interested in the chemical defense mechanisms of these soft and "shell-less" snails. Numbers of small molecules of dietary origin have been isolated from sea hares and some have ecologically relevant activities, such as fish deterrent activity or toxicity. Recently, however, greater attention has been paid to biomedically interesting sea hare isolates such as dolastatins, a series of antitumor peptide/macrolides isolated from Dolabella auricularia. Another series of bioactive peptide/macrolides, as represented by aplyronines, have been isolated from sea hares in Japanese waters. Although earlier studies indicated the potent antitumor activity of aplyronines, their clinical development has never been conducted because of the minute amount of compound available from the natural source. Recent synthetic studies, however, have made it possible to prepare these compounds and analogs for a structure-activity relationship study, and started to uncover their unique action mechanism towards their putative targets, microfilaments. Here, recent findings of small antitumor molecules isolated from Japanese sea hares are reviewed. Sea hares are also known to produce cytotoxic and antimicrobial proteins. In contrast to the small molecules of dietary origin, proteins are the genetic products of sea hares and they are likely to have some primary physiological functions in addition to ecological roles in the sea hare. Based on the biochemical properties and phylogenetic analysis of these proteins, we propose that they belong to one family of molecule, the "Aplysianin A family," although their molecular weights are apparently divided into two groups. Interestingly, the active principles in Aplysia species and Dolabella auricularia were shown to be L-amino acid oxidase (LAAO), a flavin enzyme that oxidizes an alpha-amino group of the substrate with

  17. Imaging of conformational changes

    Energy Technology Data Exchange (ETDEWEB)

    Michl, Josef [Univ. of Colorado, Boulder, CO (United States)

    2016-03-13

    Control of intramolecular conformational change in a small number of molecules or even a single one by an application of an outside electric field defined by potentials on nearby metal or dielectric surfaces has potential applications in both 3-D and 2-D nanotechnology. Specifically, the synthesis, characterization, and understanding of designed solids with controlled built-in internal rotational motion of a dipole promises a new class of materials with intrinsic dielectric, ferroelectric, optical and optoelectronic properties not found in nature. Controlled rotational motion is of great interest due to its expected utility in phenomena as diverse as transport, current flow in molecular junctions, diffusion in microfluidic channels, and rotary motion in molecular machines. A direct time-resolved observation of the dynamics of motion on ps or ns time scale in a single molecule would be highly interesting but is also very difficult and has yet to be accomplished. Much can be learned from an easier but still challenging comparison of directly observed initial and final orientational states of a single molecule, which is the basis of this project. The project also impacts the understanding of surface-enhanced Raman spectroscopy (SERS) and single-molecule spectroscopic detection, as well as the synthesis of solid-state materials with tailored properties from designed precursors.

  18. Bioactivity and structural properties of chimeric analogs of the starfish SALMFamide neuropeptides S1 and S2.

    Science.gov (United States)

    Jones, Christopher E; Otara, Claire B; Younan, Nadine D; Viles, John H; Elphick, Maurice R

    2014-10-01

    The starfish SALMFamide neuropeptides S1 (GFNSALMFamide) and S2 (SGPYSFNSGLTFamide) are the prototypical members of a family of neuropeptides that act as muscle relaxants in echinoderms. Comparison of the bioactivity of S1 and S2 as muscle relaxants has revealed that S2 is ten times more potent than S1. Here we investigated a structural basis for this difference in potency by comparing the bioactivity and solution conformations (using NMR and CD spectroscopy) of S1 and S2 with three chimeric analogs of these peptides. A peptide comprising S1 with the addition of S2's N-terminal tetrapeptide (Long S1 or LS1; SGPYGFNSALMFamide) was not significantly different to S1 in its bioactivity and did not exhibit concentration-dependent structuring seen with S2. An analog of S1 with its penultimate residue substituted from S2 (S1(T); GFNSALTFamide) exhibited S1-like bioactivity and structure. However, an analog of S2 with its penultimate residue substituted from S1 (S2(M); SGPYSFNSGLMFamide) exhibited loss of S2-type bioactivity and structural properties. Collectively, our data indicate that the C-terminal regions of S1 and S2 are the key determinants of their differing bioactivity. However, the N-terminal region of S2 may influence its bioactivity by conferring structural stability in solution. Thus, analysis of chimeric SALMFamides has revealed how neuropeptide bioactivity is determined by a complex interplay of sequence and conformation.

  19. Superspace conformal field theory

    Energy Technology Data Exchange (ETDEWEB)

    Quella, Thomas [Koeln Univ. (Germany). Inst. fuer Theoretische Physik; Schomerus, Volker [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany)

    2013-07-15

    Conformal sigma models and WZW models on coset superspaces provide important examples of logarithmic conformal field theories. They possess many applications to problems in string and condensed matter theory. We review recent results and developments, including the general construction of WZW models on type I supergroups, the classification of conformal sigma models and their embedding into string theory.

  20. Superspace conformal field theory

    International Nuclear Information System (INIS)

    Conformal sigma models and WZW models on coset superspaces provide important examples of logarithmic conformal field theories. They possess many applications to problems in string and condensed matter theory. We review recent results and developments, including the general construction of WZW models on type I supergroups, the classification of conformal sigma models and their embedding into string theory.

  1. Molecular Orbital and Density Functional Study of the Formation, Charge Transfer, Bonding and the Conformational Isomerism of the Boron Trifluoride (BF3 and Ammonia (NH3 Donor-Acceptor Complex

    Directory of Open Access Journals (Sweden)

    Dulal C. Ghosh

    2004-09-01

    Full Text Available The formation of the F3B–NH3 supermolecule by chemical interaction of its fragment parts, BF3 and NH3, and the dynamics of internal rotation about the ‘B–N’ bond have been studied in terms of parameters provided by the molecular orbital and density functional theories. It is found that the pairs of frontier orbitals of the interacting fragments have matching symmetry and are involved in the charge transfer interaction. The donation process stems from the HOMO of the donor into the LUMO of the acceptor and simultaneously, back donation stems from the HOMO of acceptor into the LUMO of the donor. The density functional computation of chemical activation in the donor and acceptor fragments, associated with the physical process of structural reorganization just prior to the event of chemical reaction, indicates that BF3 becomes more acidic and NH3 becomes more basic, compared to their separate equilibrium states. Theoretically it is observed that the chemical reaction event of the formation of the supermolecule from its fragment parts is in accordance with the chemical potential equalization principle of the density functional theory and the electronegativity equalization principle of Sanderson. The energetics of the chemical reaction, the magnitude of the net charge transfer and the energy of the newly formed bond are quite consistent, both internally and with the principle of maximum hardness, PMH. The dynamics of the internal rotation of one part with respect to the other part of the supermolecule about the ‘B–N’ bond mimics the pattern of the conformational isomerism of the isostructural ethane molecule. It is also observed that the dynamics and evolution of molecular conformations as a function of dihedral angles is also in accordance with the principle of maximum hardness, PMH. Quite consistent with spectroscopic predictions, the height of the molecule

  2. Conformal and non Conformal Dilaton Gravity

    CERN Document Server

    Alvarez, Enrique; Mart'\\in, C P

    2014-01-01

    The quantum dynamics of the gravitational field non-minimally coupled to an (also dynamical) scalar field is studied in the broken phase. For a particular value of the coupling the system is classically conformal, and can actually be understood as the group averaging of Einstein-Hilbert's action under conformal transformations. Contradicting cherished beliefs, a conformal anomaly is found in the trace of the equations of motion. To one loop order, this anomaly vanishes on shell. Arguments are given supporting the fact that this does not happen to two loop order, where the anomaly is argued to be a real physical effect.

  3. Geometry and conformations of benzenecarboxylic acids

    OpenAIRE

    IVAN GUTMAN; DALIBOR BADJUK; ZORAN MARKOVIC

    2004-01-01

    The geometry, conformations and energy of mono-, di-, and tri-carboxylic derivatives of benzene were studied by means of the AM1 molecular-orbital method. Whereas the species having no carboxylic groups in the ortho-position (benzoic, isophthalic, terephthalic, and trimesic acids) are planar in all their (stable) conformations, those possessing carboxylic groups in the ortho-position (phthalic, 1,2,3-benzenetricarboxylic, and 1,2,4-benzenetricarboxylic acids) assume a non-planar geometry, wit...

  4. Binding, conformational transition and dimerization of amyloid-β peptide on GM1-containing ternary membrane: insights from molecular dynamics simulation.

    Directory of Open Access Journals (Sweden)

    Moutusi Manna

    Full Text Available Interactions of amyloid-β (Aβ with neuronal membrane are associated with the progression of Alzheimer's disease (AD. Ganglioside GM1 has been shown to promote the structural conversion of Aβ and increase the rate of peptide aggregation; but the exact nature of interaction driving theses processes remains to be explored. In this work, we have carried out atomistic-scale computer simulations (totaling 2.65 µs to investigate the behavior of Aβ monomer and dimers in GM1-containing raft-like membrane. The oligosaccharide head-group of GM1 was observed to act as scaffold for Aβ-binding through sugar-specific interactions. Starting from the initial helical peptide conformation, a β-hairpin motif was formed at the C-terminus of the GM1-bound Aβ-monomer; that didn't appear in absence of GM1 (both in fluid POPC and liquid-ordered cholesterol/POPC bilayers and also in aqueous medium within the simulation time span. For Aβ-dimers, the β-structure was further enhanced by peptide-peptide interactions, which might influence the propensity of Aβ to aggregate into higher-ordered structures. The salt-bridges and inter-peptide hydrogen bonds were found to account for dimer stability. We observed spontaneous formation of intra-peptide D(23-K(28 salt-bridge and a turn at V(24GSN(27 region - long been accepted as characteristic structural-motifs for amyloid self-assembly. Altogether, our results provide atomistic details of Aβ-GM1 and Aβ-Aβ interactions and demonstrate their importance in the early-stages of GM1-mediated Aβ-oligomerisation on membrane surface.

  5. Study of Molecular Conformation and Activity-Related Properties of Lipase Immobilized onto Core-Shell Structured Polyacrylic Acid-Coated Magnetic Silica Nanocomposite Particles.

    Science.gov (United States)

    Esmaeilnejad-Ahranjani, Parvaneh; Kazemeini, Mohammad; Singh, Gurvinder; Arpanaei, Ayyoob

    2016-04-01

    A facile approach for the preparation of core-shell structured poly(acrylic acid) (PAA)-coated Fe3O4 cluster@SiO2 nanocomposite particles as the support materials for the lipase immobilization is reported. Low- or high-molecular-weight (1800 and 100,000, respectively) PAA molecules were covalently attached onto the surface of amine-functionalized magnetic silica nanoacomposite particles. The successful preparation of particles were verified by scanning transmission electron microscopy (STEM), X-ray diffraction (XRD), vibrating sample magnetometer (VSM), thermogravimetric analysis (TGA), zeta potential measurement, and Fourier-transform infrared (FTIR) techniques. Once lipase is covalently immobilized onto the particles with an average diameter of 210 ± 50 nm, resulting from high binding sites concentrations on the low- and high-molecular-weight PAA-coated particles, high lipase immobilization efficiencies (86.2% and 89.9%, respectively), and loading capacities (786 and 816 mg g(-1), respectively) are obtained. Results from circular dichroism (CD) analysis and catalytic activity tests reveal an increase in the β-sheet content of lipase molecules upon immobilization, along with an enhancement in their activities and stabilities. The lipases immobilized onto the low- and high-molecular-weight PAA-coated particles show maximum activities at 55 and 50 °C, respectively, which are ∼28% and ∼15% higher than that of the free lipase at its own optimum temperature (40 °C), respectively. The immobilized lipases exhibit excellent performance at broader temperature and pH ranges and high thermal and storage stabilities, as well as superior reusability. These prepared magnetic nanocomposite particles can be offered as suitable support materials for efficient immobilization of enzymes and improvement of the immobilized enzymes properties.

  6. Bioactivities of fish protein hydrolysates from defatted salmon backbones

    Directory of Open Access Journals (Sweden)

    Rasa Slizyte

    2016-09-01

    Full Text Available Bioactivities of bulk fish protein hydrolysates (FPH from defatted salmon backbones obtained with eight different commercial enzymes and their combinations were tested. All FPH showed antioxidative activity in vitro. DPPH scavenging activity increased, while iron chelating ability decreased with increasing time of hydrolysis. All FPH showed ACE inhibiting effect which depended on type of enzyme and increased with time of hydrolysis. The highest effect was found for FPH produced with Trypsin. Bromelain + Papain hydrolysates reduced the uptake of radiolabelled glucose into CaCo-2 cells, a model of human enterocytes, indicating a potential antidiabetic effect of FPH. FPH obtained by Trypsin, Bromelain + Papain and Protamex showed the highest ACE inhibitory, cellular glucose transporter (GLUT/SGLT inhibitory and in vitro antioxidative activities, respectively. Correlation was observed between the measured bioactivities, degree of hydrolysis and molecular weight profiles, supporting prolonged hydrolysis to obtain high bioactivities.

  7. Bioactivity of skeletal muscle proteolysis-inducing factors in the plasma proteins from cancer patients with weight loss.

    OpenAIRE

    Belizario, J. E.; Katz, M; Chenker, E.; I. Raw

    1991-01-01

    We determined the circulating level of bioactivity for skeletal muscle proteolysis-inducing factors (PIF) in the blood samples from cancer patients whose body weight loss was greater than 10%. The level of bioactivity was estimated by measurement of tyrosine release from isolated 1at diaphragm muscles incubated with an ultrafiltered fraction of plasma or serum proteins containing molecules from 0 to 25 kDa in molecular weight. Significant levels of bioactivity were detected in 25 of the 50 ca...

  8. Investigating the Conformational Structure and Potential Site Interactions of SOD Inhibitors on Ec-SOD in Marine Mud Crab Scylla serrata: A Molecular Modeling Approach.

    Science.gov (United States)

    Paital, Biswaranjan; Sablok, Gaurav; Kumar, Sunil; Singh, Sanjeev Kumar; Chainy, G B N

    2016-09-01

    Superoxide dismutases (SODs) act as a first line of the enzymatic antioxidant defense system to control cellular superoxide anion toxicity. Previously, several inhibitors have been widely identified and catalogued for inhibition of SOD activity; however, still the information about the mechanism of interaction and points toward the inhibitor interactions in structures of SODs in general and in extracellular (Ec)-SOD in particular is still in naive. In the present research, we present an insight to elucidate the molecular basis of interactions of SOD inhibitors with Ec-SOD in mud crab Scylla serrata using molecular modeling and docking approaches. Different inhibitors of SOD such as hydrogen peroxide [Formula: see text], potassium cyanide, sodium dodecyl sulfate (SDS), [Formula: see text]-mercaptoethanol and dithiocarbamate were screened to understand the potential sites that may act as sites for cleavage or blocking in the protein. SOD-SDS and [Formula: see text] complex interactions indicate residues Pro72 and Asp102 of the predicted crab Ec-SOD as common targets. The GOLD result indicates that Pro72, Asp102 and Thr103 are commonly acting as the site of interaction in Ec-SOD of S. serrata with SOD inhibitors. For the first time, the results of this study provide an insight into the structural properties of Ec-SOD of S. serrata and define the possible involvements between the amino acids present in its active sites, i.e., in the regions from 70 to 84 and from 101 to 103 and different inhibitors.

  9. Are hydrogen bonds responsible for glycine conformational preferences?

    Energy Technology Data Exchange (ETDEWEB)

    Cormanich, Rodrigo A.; Ducati, Lucas C. [Chemistry Institute, State University of Campinas, P.O. Box 6154, 13083-970 Campinas, SP (Brazil); Rittner, Roberto, E-mail: rittner@iqm.unicamp.br [Chemistry Institute, State University of Campinas, P.O. Box 6154, 13083-970 Campinas, SP (Brazil)

    2011-08-25

    Highlights: {yields} Glycine conformational preferences in the isolated state were fully investigated. {yields} The lowest energy conformation is not stabilized by hydrogen bonding. {yields} Steric and hyperconjugative effects were analyzed for all conformers. {yields} Several theoretical methods were used to explain the conformational preferences. - Abstract: Glycine conformational preferences have mostly been explained as due to the formation of intramolecular hydrogen bonding, despite other possible relevant intramolecular interactions that may be present in this molecular system. This paper, within the framework of the quantum theory of atoms in molecules and natural bond orbital analysis, at the B3LYP/aug-cc-pVDZ level, shows that hydrogen bonding formally stabilizes just one of the glycine conformers. Indeed, these theoretical calculations suggest that both steric hindrance and hyperconjugative effects rule conformational preferences of this model compound and may not be ignored in discussions of amino acid conformational analyses.

  10. Bioactive glasses: Frontiers and challenges

    Directory of Open Access Journals (Sweden)

    Larry L. Hench

    2015-11-01

    Full Text Available Bioactive glasses were discovered in 1969 and provided for the first time an alternative to nearly inert implant materials. Bioglass formed a rapid, strong and stable bond with host tissues. This article examines the frontiers of research crossed to achieve clinical use of bioactive glasses and glass-ceramics. In the 1980’s it was discovered that bioactive glasses could be used in particulate form to stimulate osteogenesis, which thereby led to the concept of regeneration of tissues. Later, it was discovered that the dissolution ions from the glasses behaved like growth factors, providing signals to the cells. This article summarizes the frontiers of knowledge crossed during four eras of development of bioactive glasses that have led from concept of bioactivity to widespread clinical and commercial use, with emphasis on the first composition, 45S5 Bioglass®. The four eras are: a discovery; b clinical application; c tissue regeneration; and d innovation. Questions still to be answered for the fourth era are included to stimulate innovation in the field and exploration of new frontiers that can be the basis for a general theory of bioactive stimulation of regeneration of tissues and application to numerous clinical needs.

  11. Bioactive proteins from pipefishes

    Institute of Scientific and Technical Information of China (English)

    E. Rethna Priya; S. Ravichandran; R. Ezhilmathi

    2013-01-01

    Objective: To screen antimicrobial potence of some pipefish species collected from Tuticorin coastal environment.Methods:Antimicrobial activity of pipefishes in methanol extract was investigated against 10 bacterial and 10 fungal human pathogenic strains.Results:Among the tested strains, in Centriscus scutatus, pipefish showed maximum zone of inhibition against Vibrio cholerae (8 mm) and minimum in the sample of Hippichthys cyanospilos against Klebseilla pneumoniae (2 mm). In positive control, maximum zone of inhibition was recorded in Vibrio cholerae (9 mm) and minimum in Klebseilla pneumoniae, and Salmonella paratyphi (5 mm). Chemical investigation indicated the presence of peptides as evidenced by ninhydrin positive spots on thin layer chromatography and presence of peptide. In SDS PAGE, in Centriscus scutatus, four bands were detected in the gel that represented the presence of proteins in the range nearly 25.8-75 kDa. In Hippichthys cyanospilos, five bands were detected in the gel that represented the presence of proteins in the range nearly 20.5-78 kDa. The result of FT-IR spectrum revealed that the pipe fishes extracts compriseed to have peptide derivatives as their predominant chemical groups.Conclusions:It can be conclude that this present investigation suggests the tested pipe fishes will be a potential source of natural bioactive compounds.

  12. The Effect of Conformational Variability of Phosphotriesterase upon N-acyl-L-homoserine Lactone and Paraoxon Binding: Insights from Molecular Dynamics Studies

    Directory of Open Access Journals (Sweden)

    Dongling Zhan

    2013-12-01

    Full Text Available The organophosphorous hydrolase (PTE from Brevundimonas diminuta is capable of degrading extremely toxic organophosphorous compounds with a high catalytic turnover and broad substrate specificity. Although the natural substrate for PTE is unknown, its loop remodeling (loop 7-2/H254R led to the emergence of a homoserine lactonase (HSL activity that is undetectable in PTE (kcat/km values of up to 2 × 104, with only a minor decrease in PTE paraoxonase activity. In this study, homology modeling and molecular dynamics simulations have been undertaken seeking to explain the reason for the substrate specificity for the wild-type and the loop 7-2/H254R variant. The cavity volume estimated results showed that the active pocket of the variant was almost two fold larger than that of the wild-type (WT enzyme. pKa calculations for the enzyme (the WT and the variant showed a significant pKa shift from WT standard values (ΔpKa = 3.5 units for the His254residue (in the Arg254 variant. Molecular dynamics simulations indicated that the displacement of loops 6 and 7 over the active site in loop 7-2/H254R variant is useful for N-acyl-L-homoserine lactone (C4-HSL with a large aliphatic chain to site in the channels easily. Thence the expanding of the active pocket is beneficial to C4-HSL binding and has a little effect on paraoxon binding. Our results provide a new theoretical contribution of loop remodeling to the rapid divergence of new enzyme functions.

  13. Gymnastics of molecular chaperones.

    Science.gov (United States)

    Mayer, Matthias P

    2010-08-13

    Molecular chaperones assist folding processes and conformational changes in many proteins. In order to do so, they progress through complex conformational cycles themselves. In this review, I discuss the diverse conformational dynamics of the ATP-dependent chaperones of the Hsp60, Hsp70, Hsp90, and Hsp100 families. PMID:20705236

  14. Molecular dynamic study of MlaC protein in Gram-negative bacteria: conformational flexibility, solvent effect and protein-phospholipid binding.

    Science.gov (United States)

    Huang, Yu-Ming M; Miao, Yinglong; Munguia, Jason; Lin, Leo; Nizet, Victor; McCammon, J Andrew

    2016-08-01

    The composition of the outer membrane in Gram-negative bacteria is asymmetric, with the lipopolysaccharides found in the outer leaflet and phospholipids in the inner leaflet. The MlaC protein transfers phospholipids from the outer to inner membrane to maintain such lipid asymmetry in the Mla pathway. In this work, we have performed molecular dynamics simulations on apo and phospholipid-bound systems to study the dynamical properties of MlaC. Our simulations show that the phospholipid forms hydrophobic interactions with the protein. Residues surrounding the entrance of the binding site exhibit correlated motions to control the site opening and closing. Lipid binding leads to increase of the binding pocket volume and precludes entry of the water molecules. However, in the absence of the phospholipid, water molecules can freely move in and out of the binding site when the pocket is open. Dehydration occurs when the pocket closes. This study provides dynamic information of the MlaC protein and may facilitate the design of antibiotics against the Mla pathway of Gram-negative bacteria. PMID:27111825

  15. Investigating the influence of effective parameters on molecular characteristics of bovine serum albumin nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Rohiwal, S.S.; Satvekar, R.K.; Tiwari, A.P.; Raut, A.V.; Kumbhar, S.G.; Pawar, S.H., E-mail: pawar_s_h@yahoo.com

    2015-04-15

    Graphical abstract: The physiochemical properties of nanoparticles provide the basic aspects about the conformational transitions which could have a strong bearing on the bioavailability for bioactive molecules such as peptides and hormones. - Highlights: • Synthesis and surface and structural properties of Bovine Serum Albumin nanoparticles (BSANPs). • Study of conformational transitions of BSANPs by spectroscopic techniques. • Studies on the effect of pH and protein concentration on formulation of BSANPs. - Abstract: The protein nanoparticles formulation is a challenging task as they are prone to undergo conformational transitions while processing which may affect bioavailability for bioactive compounds. Herein, a modified desolvation method is employed to prepare Bovine Serum Albumin nanoparticles, with controllable particle size ranging from 100 to 300 nm and low polydispersity index. The factors influencing the size and structure of BSA NPs viz. protein concentration, pH and the conditions for purification are well investigated. The structure of BSA NPs is altered due to processing, and may affect the effective binding ability with drugs and bioactive compounds. With that aims, investigations of molecular characteristics of BSA NPs are carried out in detail by using spectroscopic techniques. UV–visible absorption and Fourier Transform Infrared demonstrate the alteration in protein structure of BSA NPs whereas the FT-Raman spectroscopy investigates changes in the secondary and tertiary structures of the protein. The conformational changes of BSA NPs are observed by change in fluorescence intensity and emission maximum wavelength of tryptophan residue by fluorescence spectroscopy. The field emission scanning electron and atomic force microscopy micrographs confirm the size and semi-spherical morphology of the BSA NPs. The effect of concentration and pH on particle size distribution is studied by particle size analyzer.

  16. Investigating the influence of effective parameters on molecular characteristics of bovine serum albumin nanoparticles

    International Nuclear Information System (INIS)

    Graphical abstract: The physiochemical properties of nanoparticles provide the basic aspects about the conformational transitions which could have a strong bearing on the bioavailability for bioactive molecules such as peptides and hormones. - Highlights: • Synthesis and surface and structural properties of Bovine Serum Albumin nanoparticles (BSANPs). • Study of conformational transitions of BSANPs by spectroscopic techniques. • Studies on the effect of pH and protein concentration on formulation of BSANPs. - Abstract: The protein nanoparticles formulation is a challenging task as they are prone to undergo conformational transitions while processing which may affect bioavailability for bioactive compounds. Herein, a modified desolvation method is employed to prepare Bovine Serum Albumin nanoparticles, with controllable particle size ranging from 100 to 300 nm and low polydispersity index. The factors influencing the size and structure of BSA NPs viz. protein concentration, pH and the conditions for purification are well investigated. The structure of BSA NPs is altered due to processing, and may affect the effective binding ability with drugs and bioactive compounds. With that aims, investigations of molecular characteristics of BSA NPs are carried out in detail by using spectroscopic techniques. UV–visible absorption and Fourier Transform Infrared demonstrate the alteration in protein structure of BSA NPs whereas the FT-Raman spectroscopy investigates changes in the secondary and tertiary structures of the protein. The conformational changes of BSA NPs are observed by change in fluorescence intensity and emission maximum wavelength of tryptophan residue by fluorescence spectroscopy. The field emission scanning electron and atomic force microscopy micrographs confirm the size and semi-spherical morphology of the BSA NPs. The effect of concentration and pH on particle size distribution is studied by particle size analyzer

  17. Conformational elasticity theory of chain molecules

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    This paper develops a conformational elasticity theory of chain molecules, which is based on three key points: (ⅰ) the molecular model is the rotational isomeric state (RIS) model; (ⅱ) the conformational distribution function of a chain molecule is described by a function of two variables, the end-to-end distance of a chain conformation and the energy of the conformation; (ⅲ) the rule of changes in the chain conformational states during deformation is that a number of chain conformations would vanish. The ideal deformation behavior calculated by the theory shows that the change in chain conformations is physically able to make the upward curvature of the stress-strain curve at the large-scale deformation of natural rubber. With the theory, different deformation behaviors between polymers with different chemical structures can be described, the energy term of the stress in the deformations can be predicted, and for natural rubber the fraction of the energy term is around 13%, coinciding with the experimental results.

  18. Conformal Bootstrap in Embedding Space

    CERN Document Server

    Fortin, Jean-François

    2016-01-01

    It is shown how to obtain conformal blocks from embedding space with the help of the operator product expansion. The minimal conformal block originates from scalar exchange in a four-point correlation functions of four scalars. All remaining conformal blocks are simple derivatives of the minimal conformal block. With the help of the orthogonality properties of the conformal blocks, the analytic conformal bootstrap can be implemented directly in embedding space, leading to a Jacobi-like definition of conformal field theories.

  19. Conformal bootstrap in embedding space

    Science.gov (United States)

    Fortin, Jean-François; Skiba, Witold

    2016-05-01

    It is shown how to obtain conformal blocks from embedding space with the help of the operator product expansion. The minimal conformal block originates from scalar exchange in a four-point correlation function of four scalars. All remaining conformal blocks are simple derivatives of the minimal conformal block. With the help of the orthogonality properties of the conformal blocks, the analytic conformal bootstrap can be implemented directly in embedding space, leading to a Jacobi-like definition of conformal field theories.

  20. Synthesis and in vitro bioactivity of mesoporous bioactive glass scaffolds

    Energy Technology Data Exchange (ETDEWEB)

    Shih, C.J., E-mail: cjshih@kmu.edu.tw [Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Chen, H.T. [Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Huang, L.F. [School of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Lu, P.S.; Chang, H.F. [Department of Fragrance and Cosmetic Science, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Chang, I.L., E-mail: 84004@cch.org.tw [Department of Orthopaedic Surgery, Chang-Hua Christian Hospital, Changhua 500, Taiwan (China)

    2010-06-15

    The main objective of the present study was to determine the effect of thermal treatment procedures (calcination temperature, heating rate and duration time) on the synthesis of SiO{sub 2}-CaO-P{sub 2}O{sub 5} mesoporous bioactive glass scaffolds. This is accomplished by thermogravimetric analyses, Fourier transform infrared (FTIR) absorption spectra, X-ray diffraction (XRD) and by analysis of nitrogen adsorption/desorption isotherms. In vitro bioactivity can also be assessed by the cytotoxic effect of the glasses on the NIH-3T3 cell line, and by characterization of MC-3T3-E1 cell attachment.

  1. Synthesis and in vitro bioactivity of mesoporous bioactive glass scaffolds

    International Nuclear Information System (INIS)

    The main objective of the present study was to determine the effect of thermal treatment procedures (calcination temperature, heating rate and duration time) on the synthesis of SiO2-CaO-P2O5 mesoporous bioactive glass scaffolds. This is accomplished by thermogravimetric analyses, Fourier transform infrared (FTIR) absorption spectra, X-ray diffraction (XRD) and by analysis of nitrogen adsorption/desorption isotherms. In vitro bioactivity can also be assessed by the cytotoxic effect of the glasses on the NIH-3T3 cell line, and by characterization of MC-3T3-E1 cell attachment.

  2. S-Adenosylmethionine conformations in solution and in protein complexes: Conformational influences of the sulfonium group

    DEFF Research Database (Denmark)

    Markham, George D.; Norrby, Per-Ola; Bock, Charles W.

    2002-01-01

    S-Adenosylmethionine (AdoMet) and other sulfonium ions play central roles in the metabolism of all organisms. The conformational preferences of AdoMet and two other biologically important sulfonium ions, S-methylmethionine and dimethylsulfonioproprionic acid, have been investigated by NMR...... and computational studies. Molecular mechanics parameters for the sulfonium center have been developed for the AMBER force field to permit analysis of NMR results and to enable comparison of the relative energies of the different conformations of AdoMet that have been found in crystal structures of complexes...... with proteins. S-Methylmethionine and S-dimethylsulfonioproprionate adopt a variety of conformations in aqueous solution; a conformation with an electrostatic interaction between the sulfonium sulfur and the carboxylate group is not noticeably favored, in contrast to the preferred conformation found by in vacuo...

  3. Conformational stability of calreticulin

    DEFF Research Database (Denmark)

    Jørgensen, Charlotte S; Trandum, Christa; Larsen, Nanna Brink;

    2005-01-01

    The conformational stability of calreticulin was investigated. Apparent unfolding temperatures (Tm) increased from 31 degrees C at pH 5 to 51 degrees C at pH 9, but electrophoretic analysis revealed that calreticulin oligomerized instead of unfolding. Structural analyses showed that the single C......-terminal alpha-helix was of major importance to the conformational stability of calreticulin....

  4. Conformational stability of calreticulin

    DEFF Research Database (Denmark)

    Jørgensen, C.S.; Trandum, C.; Larsen, N.;

    2005-01-01

    The conformational stability of calreticulin was investigated. Apparent unfolding temperatures (T-m) increased from 31 degrees C at pH 5 to 51 degrees C at pH 9, but electrophoretic analysis revealed that calreticulin oligomerized instead of unfolding. Structural analyses showed that the single C......-terminal a-helix was of major importance to the conformational stability of calreticulin....

  5. 低温干燥过程中LEA蛋白对胰岛素结构稳定性的研究%Investigation on Bioactive Protection of LEA Protein for Insulin by Molecular Simulation in the Low-temperature Drying Process

    Institute of Scientific and Technical Information of China (English)

    李代禧; 张燕; 郭柏松; 刘宝林; 杨春生; 刘亚茹; 翟振

    2013-01-01

    当前蛋白药物日益在许多疾病的诊断、预防和治疗方面表现出重要的作用.然而,蛋白药物具有热敏性的特点,其活性结构大多不够稳定.因此,研究热敏性蛋白药物的有效保护方法并探究其保护机制对热敏蛋白药物的生产、贮存和应用具有重大的研究意义和实用价值.本文选择胰岛素为热敏性蛋白药物,胚胎发育晚期丰富(LEA)蛋白为活性保护剂,通过分子模拟方法详细研究了LEA蛋白对胰岛素生物活性的保护作用.研究结果表明:与没有任何保护的胰岛素的活性三维结构相比,LEA蛋白对胰岛素活性三维结构具有良好的保护作用,而且受保护的胰岛素的二级结构也非常稳定.由此可见,LEA蛋白是一个优良的热敏蛋白药物活性保护剂.%Nowadays various protein medicines are increasingly playing significant roles in the treatment of many diseases,but the bioactive structures of such kinds of protein medicines are unstable because they are heat sensitive.Therefore,it is very important to explore a protective method and to explain the protective mechanism of protein medicines.In the present research,insulin was chosen as a heat-sensitive protein medicine,and a Group 3 late embryogenesis abundant (LEA) protein was chosen as its bioactive protectant during desiccation.The results of replica exchange molecular dynamics simulation suggest that comparing with insulin without any protection,the bioactive 3D structure and secondary structure of the insulin protected by LEA protein were preserved very well.All analyzing results proved that the LEA protein was a good bioactive protectant for heat sensitive protein medicines.

  6. Conformational, NBO, NLO, HOMO-LUMO, NMR, electronic spectral study and molecular docking study of N,N-Dimethyl-3-(10H-phenothiazin-10-yl)-1-propanamine

    Science.gov (United States)

    Resmi, K. S.; Haruna, Kabiru; Mary, Y. Sheena; Panicker, C. Yohannan; Saleh, Tawfik A.; Al-Saadi, Abdulaziz A.; Van Alsenoy, Christian

    2016-10-01

    FT-IR and FT-Raman spectra of N,N-Dimethyl-3-(10H-phenothiazin-10-yl)-1-propanamine were recorded and analyzed. The conformational behaviour is also investigated. The vibrational wave numbers were calculated using density functional quantum chemical calculations. The data obtained from wave number calculations are used to assign vibrational bands obtained experimentally. In the most stable form for N,N-Dimethyl-3-(10H-phenothiazin-10-yl)-1-propanamine, the nitrogen atom of the phenothiazine ring is predicted to adopt an expanded pyramidal configuration with an average Csbnd Nsbnd C angle of 118° while the alkylamine chain points away from the phenothiazine ring. The geometrical parameters are compared with related structures. The stability of the molecule arising from hyper conjugative interaction and charge delocalization has been analyzed using natural bonding orbital analysis. The frontier molecular orbital analysis is used to determine the charge transfer within the molecule. The theoretical NMR spectral analysis, Fukui functions and electronic transition UV-Vis spectral analysis is also reported. The docked title compound forms a stable complex with Plasmodium falciparum and gives a binding affinity value of -6.8 kcal/mol and the results suggest that the compound might exhibit inhibitory activity against Plasmodium falciparum.

  7. Bioactive saponins from Dioscorea futschauensis.

    Science.gov (United States)

    Liu, H W; Hu, K; Zhao, Q C; Cui, C B; Kobayashi, H; Yao, X S

    2002-08-01

    A new anti-neoplastic spirostanol saponin, (25S)-spirost-5-en-3 beta, 27-diol-3O-[alpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranosyl (1-->3)]-beta-D-glucopyranoside and three known compounds viz. prosapogenin A of dioscin, dioscin and gracilin were isolated from Dioscorea futschauensis by bioactivity-guided fractionation. Their structures were elucidated mainly by means of spectroscopic analysis. Their bioactivity against Pyricularia oryzae and cytotoxic activity on ts-FT210 cell line was evaluated. PMID:12227201

  8. The application of HP-GFC chromatographic method for the analysis of oligosaccharides in bioactive complexes

    Directory of Open Access Journals (Sweden)

    Savić Ivan

    2009-01-01

    Full Text Available The aim of this work was to optimize a GFC method for the analysis of bioactive metal (Cu, Co and Fe complexes with olygosaccharides (dextran and pullulan. Bioactive metal complexes with olygosaccharides were synthesized by original procedure. GFC was used to study the molecular weight distribution, polymerization degree of oligosaccharides and bioactive metal complexes. The metal bounding in complexes depends on the ligand polymerization degree and the presence of OH groups in coordinative sphere of the central metal ion. The interaction between oligosaccharide and metal ions are very important in veterinary medicine, agriculture, pharmacy and medicine.

  9. Preparation and bioactivity of sol-gel macroporous bioactive glass

    Institute of Scientific and Technical Information of China (English)

    Zhihua Zhou; Jianming Ruan; Jianpeng Zou; Zhongcheng Zhou

    2008-01-01

    Bioactive glass is well known for its ability of bone regeneration, and sol-gel bioactive glass has many advantages com-pared with melt-derived bioactive glass. 3-D scaffold prepared by the sol-gel method is a promising substrate material for bone tissue engineering and large-scale bone repair. Porous sol-gel glass in the CaO-SiO2-P2O5 system with macropores larger than 100 μm was prepared by the addition of stearic acid as a pore former. The diameter of the pore created by the pore former varied from 100 to 300μm. The formation of a hydroxyapatite layer on the glass was analyzed by studying the surface of the porous glass by scanning elec-tron microscopy, energy dispersive spectroscopy, X-ray diffraction, and Raman spectra after they had been immersed in simulated body fluid (SBF) for some time, and the porous glass shows good bioactivity.

  10. Selected adjunct cultures remarkably increase the content of bioactive peptides in Bulgarian white brined cheese

    OpenAIRE

    Dimitrov, Zhechko; Chorbadjiyska, Elena; Gotova, Irina; Pashova, Kalinka; Ilieva, Svetla

    2014-01-01

    Some lactic acid bacteria strains in milk media are capable of releasing bioactive peptides. In this study, we evaluated the angiotensin-converting enzyme (ACE)inhibitory activity of 180 lactic acid bacteria and selected several Lactobacillus helveticus, L. delbrueckii subsp. bulgaricus and L. casei strains that demonstrated strong ACE-inhibitory activity. The aim was to carry out a molecular study on the bioactive peptides released by the strains with the best ACE-inhibitory properties and b...

  11. Bioactivity of Minor Milk Components

    DEFF Research Database (Denmark)

    Nguyen, Duc Ninh

    of infant formula. Thereafter, bioactive milk components which were preserved in gently-processed infant formula were selected for further investigation of their immunomodulatory activity in cell and preterm pig models. We hope this project will contribute to the research on the development of new...

  12. Influence of Tableting on the Conformation and Thermal Stability of Trypsin as a Model Protein

    DEFF Research Database (Denmark)

    Klukkert, Marten; Van De Weert, Marco; Fanø, Mathias;

    2015-01-01

    reversible upon tablet reconstitution. Aqueous-state IR spectroscopy combined with partial least squares was shown to be a powerful tool to follow irreversible structural changes and evaluate sample bioactivity. Besides its conformation, the thermal stability of trypsin was altered as a result of the applied...

  13. Conformal expansions and renormalons

    CERN Document Server

    Gardi, E; Gardi, Einan; Grunberg, Georges

    2001-01-01

    The large-order behaviour of QCD is dominated by renormalons. On the other hand renormalons do not occur in conformal theories, such as the one describing the infrared fixed-point of QCD at small beta_0 (the Banks--Zaks limit). Since the fixed-point has a perturbative realization, all-order perturbative relations exist between the conformal coefficients, which are renormalon-free, and the standard perturbative coefficients, which contain renormalons. Therefore, an explicit cancellation of renormalons should occur in these relations. The absence of renormalons in the conformal limit can thus be seen as a constraint on the structure of the QCD perturbative expansion. We show that the conformal constraint is non-trivial: a generic model for the large-order behaviour violates it. We also analyse a specific example, based on a renormalon-type integral over the two-loop running-coupling, where the required cancellation does occur.

  14. [Conformers of carnosine].

    Science.gov (United States)

    Kliuev, S A

    2006-01-01

    The geometric and energetic parameters of most stable conformations of carnosine were calculated by the semiempirical guantum-chemical method PM3. The carnosine-water-zinc (II) clusters were simulated. PMID:16909845

  15. Quantum massive conformal gravity

    International Nuclear Information System (INIS)

    We first find the linear approximation of the second plus fourth order derivative massive conformal gravity action. Then we reduce the linearized action to separated second order derivative terms, which allows us to quantize the theory by using the standard first order canonical quantization method. It is shown that quantum massive conformal gravity is renormalizable but has ghost states. A possible decoupling of these ghost states at high energies is discussed. (orig.)

  16. Delineating the conformal window

    DEFF Research Database (Denmark)

    Frandsen, Mads Toudal; Pickup, Thomas; Teper, Michael

    2011-01-01

    We identify and characterise the conformal window in gauge theories relevant for beyond the standard model building, e.g. Technicolour, using the criteria of metric confinement and causal analytic couplings, which are known to be consistent with the phase diagram of supersymmetric QCD from Seiberg...... duality. Using these criteria we find perturbation theory to be consistent throughout the predicted conformal window for several of these gauge theories and we discuss recent lattice results in the light of our findings....

  17. Quantum massive conformal gravity

    OpenAIRE

    Faria, F. F.

    2016-01-01

    We first find the linear approximation of the second plus fourth order derivative massive conformal gravity action. Then we reduce the linearized action to separated second order derivative terms, which allows us to quantize the theory by using the standard first order canonical quantization method. It is shown that quantum massive conformal gravity is renormalizable but has ghost states. A possible decoupling of these ghost states at high energies is discussed.

  18. Quantum massive conformal gravity

    Science.gov (United States)

    Faria, F. F.

    2016-04-01

    We first find the linear approximation of the second plus fourth order derivative massive conformal gravity action. Then we reduce the linearized action to separated second order derivative terms, which allows us to quantize the theory by using the standard first order canonical quantization method. It is shown that quantum massive conformal gravity is renormalizable but has ghost states. A possible decoupling of these ghost states at high energies is discussed.

  19. Quantum massive conformal gravity

    Energy Technology Data Exchange (ETDEWEB)

    Faria, F.F. [Universidade Estadual do Piaui, Centro de Ciencias da Natureza, Teresina, PI (Brazil)

    2016-04-15

    We first find the linear approximation of the second plus fourth order derivative massive conformal gravity action. Then we reduce the linearized action to separated second order derivative terms, which allows us to quantize the theory by using the standard first order canonical quantization method. It is shown that quantum massive conformal gravity is renormalizable but has ghost states. A possible decoupling of these ghost states at high energies is discussed. (orig.)

  20. Geometry and conformations of benzenecarboxylic acids

    Directory of Open Access Journals (Sweden)

    IVAN GUTMAN

    2004-11-01

    Full Text Available The geometry, conformations and energy of mono-, di-, and tri-carboxylic derivatives of benzene were studied by means of the AM1 molecular-orbital method. Whereas the species having no carboxylic groups in the ortho-position (benzoic, isophthalic, terephthalic, and trimesic acids are planar in all their (stable conformations, those possessing carboxylic groups in the ortho-position (phthalic, 1,2,3-benzenetricarboxylic, and 1,2,4-benzenetricarboxylic acids assume a non-planar geometry, with one carboxyl group almost orthogonal to the plane of the benzene ring. Various rotamers of each of the studied benzenecarboxylic acids have nearly the same energy.

  1. Dynamics and Conformational Energetics of a Peptide Hormone: Vasopressin

    Science.gov (United States)

    Hagler, A. T.; Osguthorpe, D. J.; Dauber-Osguthorpe, P.; Hempel, J. C.

    1985-03-01

    A theoretical methodology for use in conjunction with experiment was applied to the neurohypophyseal hormone lysine vasopressin for elucidation of its accessible molecular conformations and associated flexibility, conformational transitions, and dynamics. Molecular dynamics and energy minimization techniques make possible a description of the conformational properties of a peptide in terms of the precise positions of atoms, their fluctuations in time, and the interatomic forces acting on them. Analysis of the dynamic trajectory of lysine vasopressin shows the ability of a flexible peptide hormone to undergo spontaneous conformational transitions. The excursions of an individual phenylalanine residue exemplify the dynamic flexibility and multiple conformational states available to small peptide hormones and their component residues, even within constraints imposed by a cyclic hexapeptide ring.

  2. Conformation of 1,2-Dimethoxyethane in Water

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    To understand the conformation of 1,2-dimethoxyethane (DME) in water, a system of two kinds of molecules, DME and H2O, was focused. The interaction of various conformers of DME with water was studied by means of ab initio molecular orbital calculation with 6-31G(d)basis set. It is shown that there are two forms of interactions between the two molecules in the sys tem, the close touched (H2O attaches to the two oxygen atoms of DME) and the open touched (H2O attaches to one oxygen atom of DME) structures. The conformation of DME is remark ably influenced by the interactions. Instead the ttt conformer is preferred in the gas state, with a close touched H2O the tgt conformer becomes the most stable one. The obtained hydration ener gies show that the stabilized order of DME conformers by water is tgt>tgg'>ttt.

  3. Conformational analysis of n-pentyl acetate using microwave spectroscopy

    Science.gov (United States)

    Attig, T.; Kannengießer, R.; Kleiner, I.; Stahl, W.

    2013-08-01

    The Fourier transform microwave spectrum of n-pentyl acetate (CH3-COO-C5H11) was recorded under molecular beam conditions. The rotational constants and the centrifugal distortion constants of the most abundant and of one less abundant conformer were determined after analyzing the spectrum through comparison with theoretical calculations. The main conformer with C1 symmetry has a strong spectrum. The second observed conformer, which has CS symmetry shows a spectrum with considerably weaker intensities. The quantum chemical calculations of specific conformers were carried out at MP2/6-311++G(d,p) level. The values of the experimental rotational constants obtained by the programs XIAM and BELGI were compared to those obtained by ab initio methods. For both conformers torsional barriers of the acetyl methyl group of approximately 100 cm-1 were found. Furthermore, the geometry of the main conformer was optimized at different levels of theory.

  4. Chelating Tendencies of Bioactive Aminophosphonates

    OpenAIRE

    Kiss, Tamas; Lázár, István; Kafarski, Pawel

    1994-01-01

    The metal-binding abilities of a wide variety of bioactive aminophosphonates, from the simple aminoethanephosphonic acids to the rather large macrocyclic polyaza derivatives, are discussed with special emphasis on a comparison of the analogous carboxylic acid and phosphonic acid systems. Examples are given of the biological importance of metal ion – aminophosphonate interactions in living systems, and also of their actual and potential applicability in medicine.

  5. Bioactivity of Rumex obtusifolius (Polygonaceae)

    OpenAIRE

    Harshaw Diane; Nahar Lutfun; Vadla Brahmachari; Saif-E-Naser Gadria M.; Sarker Satyajit D.

    2010-01-01

    Rumex obtusifolius L. (Polygonaceae), commonly known as 'broad-leaf dock', is one of the most common Irish wayside weeds, and it also occurs in silage fields, on river banks, in ditches and on waste grounds. The ethnobotanical uses of this species include its use as an antidote to nettle, depurative, astringent, laxative, and tonic, and in the treatment of sores, blisters, burns, cancer and tumors. The bioactivities of n-hexane, dichloromethane (DCM) and methanol (MeOH) extracts of the leaves...

  6. Bioactive peptides in dairy products

    Directory of Open Access Journals (Sweden)

    Donata Marletta

    2010-01-01

    Full Text Available Bioactive peptides are specific protein fragments that have a positive impact on body functions and conditions and may ultimately influence health. Most of the biological activities are encrypted within the primary sequence of the native protein and can be released by enzymatic hydrolysis and proteolysis or by food processing. Milk is a rich source of bioactive peptides which may contribute to regulate the nervous, gastrointestinal and cardiovascular systems as well as the immune system, confirming the added value of dairy products that, in certain cases, can be considered functional foods. The main biological activities of these peptides and their bioavailability in dairy products are reviewed. The natural concentration of these biomolecules is quite low and, to date one of the main goals has been to realize products enriched with bioactive peptides that have beneficial effects on human health and proven safety. Even though several health-enhancing products have already been launched and their integration in the diet could help in the prevention of chronic diseases such as hypertension, cancer and osteoporosis, more clinical trials are required in order to develop a deeper understanding of the activity of biopeptides on the human physiological mechanisms and also to assess the efficacy of their effects in a long term view. New scientific data are also needed to support their commercialisation in compliance with current regulations.

  7. In situ regeneration of bioactive coatings enabled by an evolved Staphylococcus aureus sortase A

    Science.gov (United States)

    Ham, Hyun Ok; Qu, Zheng; Haller, Carolyn A.; Dorr, Brent M.; Dai, Erbin; Kim, Wookhyun; Liu, David R.; Chaikof, Elliot L.

    2016-04-01

    Surface immobilization of bioactive molecules is a central paradigm in the design of implantable devices and biosensors with improved clinical performance capabilities. However, in vivo degradation or denaturation of surface constituents often limits the long-term performance of bioactive films. Here we demonstrate the capacity to repeatedly regenerate a covalently immobilized monomolecular thin film of bioactive molecules through a two-step stripping and recharging cycle. Reversible transpeptidation by a laboratory evolved Staphylococcus aureus sortase A (eSrtA) enabled the rapid immobilization of an anti-thrombogenic film in the presence of whole blood and permitted multiple cycles of film regeneration in vitro that preserved its biological activity. Moreover, eSrtA transpeptidation facilitated surface re-engineering of medical devices in situ after in vivo implantation through removal and restoration film constituents. These studies establish a rapid, orthogonal and reversible biochemical scheme to regenerate selective molecular constituents with the potential to extend the lifetime of bioactive films.

  8. Bridging Converts a Noncytotoxic nor-Paclitaxel Derivative to a Cytotoxic Analog by Constraining it to the T-Taxol Conformation

    OpenAIRE

    Tang, Shoubin; Yang, Chao; Brodie, Peggy; Bane, Susan; Ravindra, Rudravajhala; Sharma, Shubhada; Jiang, Yi; Snyder, James P.; Kingston, David G I

    2006-01-01

    The synthesis of the bridged A-nor-paclitaxel 4 has been achieved from paclitaxel in a key test of the T-Taxol conformational hypothesis. Although the unbridged A-nor-paclitaxel 3 is essentially non-cytotoxic, the bridged analog 4 is strongly cytotoxic. This result provides strong evidence for the T-Taxol conformation as the bioactive tubulin-binding conformation of paclitaxel.

  9. Dendrimeric nanoarchitectures mediated transdermal and oral delivery of bioactives

    Directory of Open Access Journals (Sweden)

    Gajbhiye V

    2008-01-01

    Full Text Available Transdermal route is an evolving panorama in novel drug deliverance and with oral route they proffer immense potential. Most recently there is hastening in approaches for delivering bioactives via these routes, amongst them revolution has been made by dendrimers. Encapsulation and conjugation of bioactives with these virus sized robots have shown immense employment for delivery of hydrophobic and labile remedies. Transport of these nano-cruises from corner to corner of skin and through epithelial hurdle of gastrointestinal tract depends upon dendrimer characteristics. An improved thoughtful of these characteristics is an obligation for their use in these rambling fields. These characteristics embrace generation size, molecular weight, surface charge, incubation time and concentration. This context demarcates the imperative role of dendrimers in transdermal and oral drug delivery. This review also highlights concerning mechanism of convey of nanoarrays via epithelial hurdle of GIT.

  10. Charged conformal Killing spinors

    Energy Technology Data Exchange (ETDEWEB)

    Lischewski, Andree, E-mail: lischews@mathematik.hu-berlin.de [Humboldt-Universität zu Berlin, Institut für Mathematik, Rudower Chaussee 25, Room 1.310, D12489 Berlin (Germany)

    2015-01-15

    We study the twistor equation on pseudo-Riemannian Spin{sup c}-manifolds whose solutions we call charged conformal Killing spinors (CCKSs). We derive several integrability conditions for the existence of CCKS and study their relations to spinor bilinears. A construction principle for Lorentzian manifolds admitting CCKS with nontrivial charge starting from CR-geometry is presented. We obtain a partial classification result in the Lorentzian case under the additional assumption that the associated Dirac current is normal conformal and complete the classification of manifolds admitting CCKS in all dimensions and signatures ≤5 which has recently been initiated in the study of supersymmetric field theories on curved space.

  11. Oligothiophene wires: impact of torsional conformation on the electronic structure.

    Science.gov (United States)

    Kislitsyn, D A; Taber, B N; Gervasi, C F; Zhang, L; Mannsfeld, S C B; Prell, J S; Briseno, A L; Nazin, G V

    2016-02-14

    Charge transport in polymer- and oligomer-based semiconductor materials depends strongly on the structural ordering of the constituent molecules. Variations in molecular conformations influence the electronic structures of polymers and oligomers, and thus impact their charge-transport properties. In this study, we used Scanning Tunneling Microscopy and Spectroscopy (STM/STS) to investigate the electronic structures of different alkyl-substituted oligothiophenes displaying varied torsional conformations on the Au(111) surface. STM imaging showed that on Au(111), oligothiophenes self-assemble into chain-like structures, binding to each other via interdigitated alkyl ligands. The molecules adopted distinct planar conformations with alkyl ligands forming cis- or trans- mutual orientations. For each molecule, by using STS mapping, we identify a progression of particle-in-a-box-like states corresponding to the LUMO, LUMO+1 and LUMO+2 orbitals. Analysis of STS data revealed very similar unoccupied molecular orbital energies for different possible molecular conformations. By using density functional theory calculations, we show that the lack of variation in molecular orbital energies among the different oligothiophene conformers implies that the effect of the Au-oligothiophene interaction on molecular orbital energies is nearly identical for all studied torsional conformations. Our results suggest that cis-trans torsional disorder may not be a significant source of electronic disorder and charge carrier trapping in organic semiconductor devices based on oligothiophenes. PMID:26804474

  12. Hierarchical Structures and Shaped Particles of Bioactive Glass and Its In Vitro Bioactivity

    Directory of Open Access Journals (Sweden)

    U. Boonyang

    2013-01-01

    Full Text Available In this study, bioactive glass particles with controllable structure and porosity were prepared using dual-templating methods. Block copolymers used as one template component produced mesopores in the calcined samples. Polymer colloidal crystals as the other template component yielded either three-dimensionally ordered macroporous (3DOM products or shaped bioactive glass nanoparticles. The in vitro bioactivity of these bioactive glasses was studied by soaking the samples in simulated body fluid (SBF at body temperature (37°C for varying lengths of time and monitoring the formation of bone-like apatite on the surface of the bioactive glass. A considerable bioactivity was found that all of bioactive glass samples have the ability to induce the formation of an apatite layer on its surface when in contact with SBF. The development of bone-like apatite is faster for 3DOM bioactive glasses than for nanoparticles.

  13. Conformal special relativity

    International Nuclear Information System (INIS)

    It is shown that the information loss/recovery theorem based on the ADS/CFT correspondence is not consistent with the stability of the Schwarzschild or Reissner-Nordstrom black holes. Nonetheless, the conformal invariance of Yang-Mills theory points to new relativity principle compatible with quantum unitarity near those black holes

  14. Extende conformal field theories

    Energy Technology Data Exchange (ETDEWEB)

    Taormina, A. (Chicago Univ., IL (USA). Enrico Fermi Inst.)

    1990-08-01

    Some extended conformal field theories are briefly reviewed. They illustrate how non minimal models of the Virasoro algebra (c{ge}1) can become minimal with respect to a larger algebra. The accent is put on N-extended superconformal algebras, which are relevant in superstring compactification. (orig.).

  15. Extended conformal field theories

    Science.gov (United States)

    Taormina, Anne

    1990-08-01

    Some extended conformal field theories are briefly reviewed. They illustrate how non minimal models of the Virasoro algebra (c≥1) can become minimal with respect to a larger algebra. The accent is put on N-extended superconformal algebras, which are relevant in superstring compactification.

  16. Conformal General Relativity

    CERN Document Server

    Pervushin, V

    2001-01-01

    The inflation-free solution of problems of the modern cosmology (horizon, cosmic initial data, Planck era, arrow of time, singularity,homogeneity, and so on) is considered in the conformal-invariant unified theory given in the space with geometry of similarity where we can measure only the conformal-invariant ratio of all quantities. Conformal General Relativity is defined as the $SU_c(3)\\times SU(2)\\times U(1)$-Standard Model where the dimensional parameter in the Higgs potential is replaced by a dilaton scalar field described by the negative Penrose-Chernikov-Tagirov action. Spontaneous SU(2) symmetry breaking is made on the level of the conformal-invariant angle of the dilaton-Higgs mixing, and it allows us to keep the structure of Einstein's theory with the equivalence principle. We show that the lowest order of the linearized equations of motion solves the problems mentioned above and describes the Cold Universe Scenario with the constant temperature T and z-history of all masses with respect to an obser...

  17. Bioactive glasses materials, properties and applications

    CERN Document Server

    Ylänen, Heimo

    2011-01-01

    Due to their biocompatibility and bioactivity, bioactive glasses are used as highly effective implant materials throughout the human body to replace or repair damaged tissue. As a result, they have been in continuous use since shortly after their invention in the late 1960s and are the subject of extensive research worldwide.Bioactive glasses provides readers with a detailed review of the current status of this unique material, its properties, technologies and applications. Chapters in part one deal with the materials and mechanical properties of bioactive glass, examining topics such

  18. CONFORMANCE IMPROVEMENT USING GELS

    Energy Technology Data Exchange (ETDEWEB)

    Randall S. Seright

    2004-09-30

    This report describes work performed during the third and final year of the project, ''Conformance Improvement Using Gels.'' Corefloods revealed throughput dependencies of permeability reduction by polymers and gels that were much more prolonged during oil flow than water flow. This behavior was explained using simple mobility ratio arguments. A model was developed that quantitatively fits the results and predicts ''clean up'' times for oil productivity when production wells are returned to service after application of a polymer or gel treatment. X-ray computed microtomography studies of gels in strongly water-wet Berea sandstone and strongly oil-wet porous polyethylene suggested that oil penetration through gel-filled pores occurs by a gel-dehydration mechanism, rather than gel-ripping or gel-displacement mechanisms. In contrast, analysis of data from the University of Kansas suggests that the gel-ripping or displacement mechanisms are more important in more permeable, strongly water-wet sandpacks. These findings help to explain why aqueous gels can reduce permeability to water more than to oil under different conditions. Since cement is the most commonly used material for water shutoff, we considered when gels are preferred over cements. Our analysis and experimental results indicated that cement cannot be expected to completely fill (top to bottom) a vertical fracture of any width, except near the wellbore. For vertical fractures with apertures less than 4 mm, the cement slurry will simply not penetrate very far into the fracture. For vertical fractures with apertures greater than 4 mm, the slurry may penetrate a substantial distance into the bottom part of the fracture. However, except near the wellbore, the upper part of the fracture will remain open due to gravity segregation. We compared various approaches to plugging fractures using gels, including (1) varying polymer content, (2) varying placement (extrusion) rate

  19. CONFORMANCE IMPROVEMENT USING GELS

    Energy Technology Data Exchange (ETDEWEB)

    Randall S. Seright

    2003-09-01

    This report describes work performed during the second year of the project, ''Conformance Improvement Using Gels.'' The project has two objectives. The first objective is to identify gel compositions and conditions that substantially reduce flow through fractures that allow direct channeling between wells, while leaving secondary fractures open so that high fluid injection and production rates can be maintained. The second objective is to optimize treatments in fractured production wells, where the gel must reduce permeability to water much more than that to oil. Pore-level images from X-ray computed microtomography were re-examined for Berea sandstone and porous polyethylene. This analysis suggests that oil penetration through gel-filled pores occurs by a gel-dehydration mechanism, rather than a gel-ripping mechanism. This finding helps to explain why aqueous gels can reduce permeability to water more than to oil. We analyzed a Cr(III)-acetate-HPAM gel treatment in a production well in the Arbuckle formation. The availability of accurate pressure data before, during, and after the treatment was critical for the analysis. After the gel treatment, water productivity was fairly constant at about 20% of the pre-treatment value. However, oil productivity was stimulated by a factor of 18 immediately after the treatment. During the six months after the treatment, oil productivity gradually decreased to approach the pre-treatment value. To explain this behavior, we proposed that the fracture area open to oil flow was increased substantially by the gel treatment, followed by a gradual closing of the fractures during subsequent production. For a conventional Cr(III)-acetate-HPAM gel, the delay between gelant preparation and injection into a fracture impacts the placement, leakoff, and permeability reduction behavior. Formulations placed as partially formed gels showed relatively low pressure gradients during placement, and yet substantially reduced the

  20. Compact conformations of human protein disulfide isomerase.

    Directory of Open Access Journals (Sweden)

    Shang Yang

    Full Text Available Protein disulfide isomerase (PDI composed of four thioredoxin-like domains a, b, b', and a', is a key enzyme catalyzing oxidative protein folding in the endoplasmic reticulum. Large scale molecular dynamics simulations starting from the crystal structures of human PDI (hPDI in the oxidized and reduced states were performed. The results indicate that hPDI adopts more compact conformations in solution than in the crystal structures, which are stabilized primarily by inter-domain interactions, including the salt bridges between domains a and b' observed for the first time. A prominent feature of the compact conformations is that the two catalytic domains a and a' can locate close enough for intra-molecular electron transfer, which was confirmed by the characterization of an intermediate with a disulfide between the two domains. Mutations, which disrupt the inter-domain interactions, lead to decreased reductase activity of hPDI. Our molecular dynamics simulations and biochemical experiments reveal the intrinsic conformational dynamics of hPDI and its biological impact.

  1. Discovering conformational sub-states relevant to protein function.

    Directory of Open Access Journals (Sweden)

    Arvind Ramanathan

    Full Text Available BACKGROUND: Internal motions enable proteins to explore a range of conformations, even in the vicinity of native state. The role of conformational fluctuations in the designated function of a protein is widely debated. Emerging evidence suggests that sub-groups within the range of conformations (or sub-states contain properties that may be functionally relevant. However, low populations in these sub-states and the transient nature of conformational transitions between these sub-states present significant challenges for their identification and characterization. METHODS AND FINDINGS: To overcome these challenges we have developed a new computational technique, quasi-anharmonic analysis (QAA. QAA utilizes higher-order statistics of protein motions to identify sub-states in the conformational landscape. Further, the focus on anharmonicity allows identification of conformational fluctuations that enable transitions between sub-states. QAA applied to equilibrium simulations of human ubiquitin and T4 lysozyme reveals functionally relevant sub-states and protein motions involved in molecular recognition. In combination with a reaction pathway sampling method, QAA characterizes conformational sub-states associated with cis/trans peptidyl-prolyl isomerization catalyzed by the enzyme cyclophilin A. In these three proteins, QAA allows identification of conformational sub-states, with critical structural and dynamical features relevant to protein function. CONCLUSIONS: Overall, QAA provides a novel framework to intuitively understand the biophysical basis of conformational diversity and its relevance to protein function.

  2. A Conformal Extension Theorem based on Null Conformal Geodesics

    CERN Document Server

    Lübbe, Christian

    2008-01-01

    In this article we describe the formulation of null geodesics as null conformal geodesics and their description in the tractor formalism. A conformal extension theorem through an isotropic singularity is proven by requiring the boundedness of the tractor curvature and its derivatives to sufficient order along a congruence of null conformal geodesic. This article extends earlier work by Tod and Luebbe.

  3. An allosteric mechanism inferred from molecular dynamics simulations on phospholamban pentamer in lipid membranes.

    Directory of Open Access Journals (Sweden)

    Peng Lian

    Full Text Available Phospholamban functions as a regulator of Ca(2+ concentration of cardiac muscle cells by triggering the bioactivity of sarcoplasmic reticulum Ca(2+-ATPase. In order to understand its dynamic mechanism in the environment of bilayer surroundings, we performed long time-scale molecular dynamic simulations based on the high-resolution NMR structure of phospholamban pentamer. It was observed from the molecular dynamics trajectory analyses that the conformational transitions between the "bellflower" and "pinwheel" modes were detected for phospholamban. Particularly, the two modes became quite similar to each other after phospholamban was phosphorylated at Ser16. Based on these findings, an allosteric mechanism was proposed to elucidate the dynamic process of phospholamban interacting with Ca(2+-ATPase.

  4. Structure and Function of Chitosan (V). Conformations of Ethylene Glycol Derivatives of Chitin and Chitosan

    OpenAIRE

    YUI, Toshifumi; NAKATA, Kunihiko; OGAWA, Kozo

    1996-01-01

    Molecular structures of ethylene glycol derivatives of chitin and chitosan, where 0-6 of chitin chain was etherified and both 0-3 and 0-6 of chitosan were substituted, were studied by X-ray fiber diffraction methods coupled with conformational analyses. The extended two-fold helical conformations of both chitin and chitosan chains were retained even by the etherifications. Possible molecular conformations of these derivatives were proposed.

  5. Multiscale conformal pattern transfer

    Science.gov (United States)

    Lodewijks, Kristof; Miljkovic, Vladimir; Massiot, Inès; Mekonnen, Addis; Verre, Ruggero; Olsson, Eva; Dmitriev, Alexandre

    2016-06-01

    We demonstrate a method for seamless transfer from a parent flat substrate of basically any lithographic top-down or bottom-up pattern onto essentially any kind of surface. The nano- or microscale patterns, spanning macroscopic surface areas, can be transferred with high conformity onto a large variety of surfaces when such patterns are produced on a thin carbon film, grown on top of a sacrificial layer. The latter allows lifting the patterns from the flat parent substrate onto a water-air interface to be picked up by the host surface of choice. We illustrate the power of this technique by functionalizing broad range of materials including glass, plastics, metals, rough semiconductors and polymers, highlighting the potential applications in in situ colorimetry of the chemistry of materials, anti-counterfeit technologies, biomolecular and biomedical studies, light-matter interactions at the nanoscale, conformal photovoltaics and flexible electronics.

  6. Hot Conformal Gauge Theories

    DEFF Research Database (Denmark)

    Mojaza, Matin; Pica, Claudio; Sannino, Francesco

    2010-01-01

    We compute the nonzero temperature free energy up to the order g^6 \\ln(1/g) in the coupling constant for vector like SU(N) gauge theories featuring matter transforming according to different representations of the underlying gauge group. The number of matter fields, i.e. flavors, is arranged...... in such a way that the theory develops a perturbative stable infrared fixed point at zero temperature. Due to large distance conformality we trade the coupling constant with its fixed point value and define a reduced free energy which depends only on the number of flavors, colors and matter representation. We...... of flavors. Surprisingly this number, if computed to the order g^2, agrees with previous predictions for the lower boundary of the conformal window for nonsupersymmetric gauge theories. The higher order results tend to predict a higher number of critical flavors. These are universal properties, i...

  7. Conformal Complementarity Maps

    CERN Document Server

    Barbón, José L F

    2013-01-01

    We study quantum cosmological models for certain classes of bang/crunch singularities, using the duality between expanding bubbles in AdS with a FRW interior cosmology and perturbed CFTs on de Sitter space-time. It is pointed out that horizon complementarity in the AdS bulk geometries is realized as a conformal transformation in the dual deformed CFT. The quantum version of this map is described in full detail in a toy model involving conformal quantum mechanics. In this system the complementarity map acts as an exact duality between eternal and apocalyptic Hamiltonian evolutions. We calculate the commutation relation between the Hamiltonians corresponding to the different frames. It vanishes only on scale invariant states.

  8. Bioactivity of plasma implanted biomaterials

    Science.gov (United States)

    Chu, Paul K.

    2006-01-01

    Plasma immersion ion implantation and deposition (PIII&D) is an effective technique to enhance the surface bioactivity of materials. In this paper, recent progress made in our laboratory on plasma surface modification of biomedical materials is described. NiTi alloys have unique super-elastic and shape memory properties and are suitable for orthopedic implants but the leaching of toxic Ni may pose health hazards in humans. We have recently investigated the use of acetylene, oxygen and nitrogen PIII&D to prevent out-diffusion of nickel and good results have been obtained. Silicon is the most important material in the microelectronics industry but its surface biocompatibility has not been investigated in details. We have recently performed hydrogen PIII into silicon to improve the surface bioactivity and observed biomimetic growth of apatite on the surface in simulated body fluids. Diamond-like carbon (DLC) is widely used in the industry due to its excellent mechanical properties and chemical inertness and by incorporation of elements such as nitrogen and phosphorus, the surface blood compatibility can be improved. The properties as well as in vitro biological test results are discussed in this article.

  9. Bioactive components in fish venoms.

    Science.gov (United States)

    Ziegman, Rebekah; Alewood, Paul

    2015-05-01

    Animal venoms are widely recognized excellent resources for the discovery of novel drug leads and physiological tools. Most are comprised of a large number of components, of which the enzymes, small peptides, and proteins are studied for their important bioactivities. However, in spite of there being over 2000 venomous fish species, piscine venoms have been relatively underrepresented in the literature thus far. Most studies have explored whole or partially fractioned venom, revealing broad pharmacology, which includes cardiovascular, neuromuscular, cytotoxic, inflammatory, and nociceptive activities. Several large proteinaceous toxins, such as stonustoxin, verrucotoxin, and Sp-CTx, have been isolated from scorpaenoid fish. These form pores in cell membranes, resulting in cell death and creating a cascade of reactions that result in many, but not all, of the physiological symptoms observed from envenomation. Additionally, Natterins, a novel family of toxins possessing kininogenase activity have been found in toadfish venom. A variety of smaller protein toxins, as well as a small number of peptides, enzymes, and non-proteinaceous molecules have also been isolated from a range of fish venoms, but most remain poorly characterized. Many other bioactive fish venom components remain to be discovered and investigated. These represent an untapped treasure of potentially useful molecules. PMID:25941767

  10. Bioactive Egg Components and Inflammation

    Directory of Open Access Journals (Sweden)

    Catherine J. Andersen

    2015-09-01

    Full Text Available Inflammation is a normal acute response of the immune system to pathogens and tissue injury. However, chronic inflammation is known to play a significant role in the pathophysiology of numerous chronic diseases, such as cardiovascular disease, type 2 diabetes mellitus, and cancer. Thus, the impact of dietary factors on inflammation may provide key insight into mitigating chronic disease risk. Eggs are recognized as a functional food that contain a variety of bioactive compounds that can influence pro- and anti-inflammatory pathways. Interestingly, the effects of egg consumption on inflammation varies across different populations, including those that are classified as healthy, overweight, metabolic syndrome, and type 2 diabetic. The following review will discuss the pro- and anti-inflammatory properties of egg components, with a focus on egg phospholipids, cholesterol, the carotenoids lutein and zeaxanthin, and bioactive proteins. The effects of egg consumption of inflammation across human populations will additionally be presented. Together, these findings have implications for population-specific dietary recommendations and chronic disease risk.

  11. Conformable light emitting modules

    OpenAIRE

    Jablonski, Michal

    2014-01-01

    As we become increasingly aware that there is more to light than the image it forms on our retina, and as we become more environmentally aware, the value of non-image-forming light increases along with the need for various new light related appliances. In particular, some lighting related applications are emerging which demand conformability (flexibility and stretchability). Well-being, automotive or wearable electronic applications are just a few examples where these trends can be observed. ...

  12. Conformal scalar field wormholes

    Science.gov (United States)

    Halliwell, Jonathan J.; Laflamme, Raymond

    1989-01-01

    The Euclidian Einstein equations with a cosmological constant and a conformally coupled scalar field are solved, taking the metric to be of the Robertson-Walker type. In the case Lambda = 0, solutions are found which represent a wormhole connecting two asymptotically flat Euclidian regions. In the case Lambda greater than 0, the solutions represent tunneling from a small Tolman-like universe to a large Robertson-Walker universe.

  13. The conformal bootstrap

    Science.gov (United States)

    Poland, David; Simmons-Duffin, David

    2016-06-01

    The conformal bootstrap was proposed in the 1970s as a strategy for calculating the properties of second-order phase transitions. After spectacular success elucidating two-dimensional systems, little progress was made on systems in higher dimensions until a recent renaissance beginning in 2008. We report on some of the main results and ideas from this renaissance, focusing on new determinations of critical exponents and correlation functions in the three-dimensional Ising and O(N) models.

  14. Functional properties of spinach (Spinacia oleracea L.) phytochemicals and bioactives.

    Science.gov (United States)

    Roberts, Joseph L; Moreau, Régis

    2016-08-10

    Overwhelming evidence indicates that diets rich in fruits and vegetables are protective against common chronic diseases, such as cancer, obesity and cardiovascular disease. Leafy green vegetables, in particular, are recognized as having substantial health-promoting activities that are attributed to the functional properties of their nutrients and non-essential chemical compounds. Spinach (Spinacia oleracea L.) is widely regarded as a functional food due to its diverse nutritional composition, which includes vitamins and minerals, and to its phytochemicals and bioactives that promote health beyond basic nutrition. Spinach-derived phytochemicals and bioactives are able to (i) scavenge reactive oxygen species and prevent macromolecular oxidative damage, (ii) modulate expression and activity of genes involved in metabolism, proliferation, inflammation, and antioxidant defence, and (iii) curb food intake by inducing secretion of satiety hormones. These biological activities contribute to the anti-cancer, anti-obesity, hypoglycemic, and hypolipidemic properties of spinach. Despite these valuable attributes, spinach consumption remains low in comparison to other leafy green vegetables. This review examines the functional properties of spinach in cell culture, animals and humans with a focus on the molecular mechanisms by which spinach-derived non-essential phytochemicals and bioactives, such as glycolipids and thylakoids, impart their health benefits.

  15. Secondary Metabolites from Higher Fungi: Discovery, Bioactivity, and Bioproduction

    Science.gov (United States)

    Zhong, Jian-Jiang; Xiao, Jian-Hui

    Medicinal higher fungi such as Cordyceps sinensis and Ganoderma lucidum have been used as an alternative medicine remedy to promote health and longevity for people in China and other regions of the world since ancient times. Nowadays there is an increasing public interest in the secondary metabolites of those higher fungi for discovering new drugs or lead compounds. Current research in drug discovery from medicinal higher fungi involves a multifaceted approach combining mycological, biochemical, pharmacological, metabolic, biosynthetic and molecular techniques. In recent years, many new secondary metabolites from higher fungi have been isolated and are more likely to provide lead compounds for new drug discovery, which may include chemopreventive agents possessing the bioactivity of immunomodulatory, anticancer, etc. However, numerous challenges of secondary metabolites from higher fungi are encountered including bioseparation, identification, biosynthetic metabolism, and screening model issues, etc. Commercial production of secondary metabolites from medicinal mushrooms is still limited mainly due to less information about secondary metabolism and its regulation. Strategies for enhancing secondary metabolite production by medicinal mushroom fermentation include two-stage cultivation combining liquid fermentation and static culture, two-stage dissolved oxygen control, etc. Purification of bioactive secondary metabolites, such as ganoderic acids from G. lucidum, is also very important to pharmacological study and future pharmaceutical application. This review outlines typical examples of the discovery, bioactivity, and bioproduction of secondary metabolites of higher fungi origin.

  16. Functional properties of spinach (Spinacia oleracea L.) phytochemicals and bioactives.

    Science.gov (United States)

    Roberts, Joseph L; Moreau, Régis

    2016-08-10

    Overwhelming evidence indicates that diets rich in fruits and vegetables are protective against common chronic diseases, such as cancer, obesity and cardiovascular disease. Leafy green vegetables, in particular, are recognized as having substantial health-promoting activities that are attributed to the functional properties of their nutrients and non-essential chemical compounds. Spinach (Spinacia oleracea L.) is widely regarded as a functional food due to its diverse nutritional composition, which includes vitamins and minerals, and to its phytochemicals and bioactives that promote health beyond basic nutrition. Spinach-derived phytochemicals and bioactives are able to (i) scavenge reactive oxygen species and prevent macromolecular oxidative damage, (ii) modulate expression and activity of genes involved in metabolism, proliferation, inflammation, and antioxidant defence, and (iii) curb food intake by inducing secretion of satiety hormones. These biological activities contribute to the anti-cancer, anti-obesity, hypoglycemic, and hypolipidemic properties of spinach. Despite these valuable attributes, spinach consumption remains low in comparison to other leafy green vegetables. This review examines the functional properties of spinach in cell culture, animals and humans with a focus on the molecular mechanisms by which spinach-derived non-essential phytochemicals and bioactives, such as glycolipids and thylakoids, impart their health benefits. PMID:27353735

  17. Chromatographic on-line detection of bioactives in food

    Directory of Open Access Journals (Sweden)

    Remmelt Van der Werf

    2013-08-01

    Full Text Available ABSTRACTFindings were focused on the anti-oxidative activity of numerous fruits and vegetables by means of an on-line HPLC radical scavenging detection method. The reactant used was the ABTS•+ green radical cation. The system has been optimized in terms of reactor design, and chemical reactions kinetics. It has been qualified to classify molecules in order of their increasing activity to scavenge exogenous radicals. It may be used as a powerful high resolution screening tool to investigate the radical scavenging activities of natural plants. Bioassays consisting in cellular in vitro antioxidant assay using pancreatic β-cells have been used to confirm the bioactivity of the selected micronutrients. This study demonstrated that it is possible to screen at the molecular level, the bioactivity of numerous natural samples and to point out the richness of the local biodiversity in terms of natural resource of functional food ingredients usable for their potential benefits for consumer’s health, wellbeing and wellaging.Key words: HPLC radical scavenging detection method, bioactivity of natural samples

  18. Conformal boundaries of warped products

    DEFF Research Database (Denmark)

    Kokkendorff, Simon Lyngby

    2006-01-01

    In this note we prove a result on how to determine the conformal boundary of a type of warped product of two length spaces in terms of the individual conformal boundaries. In the situation, that we treat, the warping and conformal distortion functions are functions of distance to a base point....... The result is applied to produce examples of CAT(0)-spaces, where the conformal and ideal boundaries differ in interesting ways....

  19. Random Conformal Weldings

    CERN Document Server

    Astala, K; Kupiainen, A; Saksman, E

    2009-01-01

    We construct a conformally invariant random family of closed curves in the plane by welding of random homeomorphisms of the unit circle. The homeomorphism is constructed using the exponential of $\\beta X$ where $X$ is the restriction of the two dimensional free field on the circle and the parameter $\\beta$ is in the "high temperature" regime $\\beta<\\sqrt 2$. The welding problem is solved by studying a non-uniformly elliptic Beltrami equation with a random complex dilatation. For the existence a method of Lehto is used. This requires sharp probabilistic estimates to control conformal moduli of annuli and they are proven by decomposing the free field as a sum of independent fixed scale fields and controlling the correlations of the complex dilation restricted to dyadic cells of various scales. For uniqueness we invoke a result by Jones and Smirnov on conformal removability of H\\"older curves. We conjecture that our curves are locally related to SLE$(\\kappa)$ for $\\kappa<4$.

  20. Investigating the influence of effective parameters on molecular characteristics of bovine serum albumin nanoparticles

    Science.gov (United States)

    Rohiwal, S. S.; Satvekar, R. K.; Tiwari, A. P.; Raut, A. V.; Kumbhar, S. G.; Pawar, S. H.

    2015-04-01

    The protein nanoparticles formulation is a challenging task as they are prone to undergo conformational transitions while processing which may affect bioavailability for bioactive compounds. Herein, a modified desolvation method is employed to prepare Bovine Serum Albumin nanoparticles, with controllable particle size ranging from 100 to 300 nm and low polydispersity index. The factors influencing the size and structure of BSA NPs viz. protein concentration, pH and the conditions for purification are well investigated. The structure of BSA NPs is altered due to processing, and may affect the effective binding ability with drugs and bioactive compounds. With that aims, investigations of molecular characteristics of BSA NPs are carried out in detail by using spectroscopic techniques. UV-visible absorption and Fourier Transform Infrared demonstrate the alteration in protein structure of BSA NPs whereas the FT-Raman spectroscopy investigates changes in the secondary and tertiary structures of the protein. The conformational changes of BSA NPs are observed by change in fluorescence intensity and emission maximum wavelength of tryptophan residue by fluorescence spectroscopy. The field emission scanning electron and atomic force microscopy micrographs confirm the size and semi-spherical morphology of the BSA NPs. The effect of concentration and pH on particle size distribution is studied by particle size analyzer.

  1. Conformationally Gated Charge Transfer in DNA Three-Way Junctions.

    Science.gov (United States)

    Zhang, Yuqi; Young, Ryan M; Thazhathveetil, Arun K; Singh, Arunoday P N; Liu, Chaoren; Berlin, Yuri A; Grozema, Ferdinand C; Lewis, Frederick D; Ratner, Mark A; Renaud, Nicolas; Siriwong, Khatcharin; Voityuk, Alexander A; Wasielewski, Michael R; Beratan, David N

    2015-07-01

    Molecular structures that direct charge transport in two or three dimensions possess some of the essential functionality of electrical switches and gates. We use theory, modeling, and simulation to explore the conformational dynamics of DNA three-way junctions (TWJs) that may control the flow of charge through these structures. Molecular dynamics simulations and quantum calculations indicate that DNA TWJs undergo dynamic interconversion among "well stacked" conformations on the time scale of nanoseconds, a feature that makes the junctions very different from linear DNA duplexes. The studies further indicate that this conformational gating would control charge flow through these TWJs, distinguishing them from conventional (larger size scale) gated devices. Simulations also find that structures with polyethylene glycol linking groups ("extenders") lock conformations that favor CT for 25 ns or more. The simulations explain the kinetics observed experimentally in TWJs and rationalize their transport properties compared with double-stranded DNA. PMID:26266714

  2. Synthesis, crystallographic characterization, and conformational prediction of a structurally unique molecular mixed-ligand U(VI) solid, Na{sub 6}[UO{sub 2}(O{sub 2}){sub 2}(OH){sub 2}](OH){sub 2} . 14H{sub 2}O

    Energy Technology Data Exchange (ETDEWEB)

    Zehnder, R.A.; Scott, B.L.; Peper, S.M.; Goff, G.S.; Runde, W.H. [Chemistry Div., Los Alamos National Lab., NM (United States); Batista, E.R. [Theoretical Div., Los Alamos National Lab., NM (United States)

    2008-07-01

    The first mononuclear molecular mixed-ligand U(VI) solid containing hydroxide and peroxide ligands, Na{sub 6}[UO{sub 2}(O{sub 2}){sub 2}(OH){sub 2}](OH){sub 2} . 14H{sub 2}O (I), was synthesized and structurally characterized using single crystal X-ray diffraction. The crystal structure of I consisted of [UO{sub 2}(O{sub 2}){sub 2}(OH){sub 2}]{sup 4-} molecular units, with a uranyl(VI) moiety perpendicular to 6 equatorial O atoms belonging to two side-on trans peroxo groups and two terminal trans hydroxo groups. Density functional theory (DFT) calculations determined that the trans-conformer of the [UO{sub 2}(O{sub 2}){sub 2}(OH){sub 2}]{sup 4-} molecular unit found in I was 24 kcal/mol lower in energy than the previously proposed cis-conformer. Crystal data: monoclinic, space group P2{sub 1}/n with a = 13.357(4) A, b = 5.8521(15) A, c = 15.948(6) A, {beta} = 112.292(4) , and Z = 2. (orig.)

  3. Preparation, characterization, in vitro bioactivity, and cellular responses to a polyetheretherketone bioactive composite containing nanocalcium silicate for bone repair.

    Science.gov (United States)

    Ma, Rui; Tang, Songchao; Tan, Honglue; Qian, Jun; Lin, Wentao; Wang, Yugang; Liu, Changsheng; Wei, Jie; Tang, Tingting

    2014-08-13

    In this study, a nanocalcium silicate (n-CS)/polyetheretherketone (PEEK) bioactive composite was prepared using a process of compounding and injection-molding. The mechanical properties, hydrophilicity, and in vitro bioactivity of the composite, as well as the cellular responses of MC3T3-E1 cells (attachment, proliferation, spreading, and differentiation) to the composite, were investigated. The results showed that the mechanical properties and hydrophilicity of the composites were significantly improved by the addition of n-CS to PEEK. In addition, an apatite-layer formed on the composite surface after immersion in simulated body fluid (SBF) for 7 days. In cell culture tests, the results revealed that the n-CS/PEEK composite significantly promoted cell attachment, proliferation, and spreading compared with PEEK or ultrahigh molecular weight polyethylene (UHMWPE). Moreover, cells grown on the composite exhibited higher alkaline phosphatase (ALP) activity, more calcium nodule-formation, and higher expression levels of osteogenic differentiation-related genes than cells grown on PEEK or UHMWPE. These results indicated that the incorporation of n-CS to PEEK could greatly improve the bioactivity and biocompatibility of the composite. Thus, the n-CS/PEEK composite may be a promising bone repair material for use in orthopedic clinics.

  4. Conformational transformations induced by the charge-curvature interaction

    OpenAIRE

    Gaididei, Yu B.; Christiansen, Peter Leth; Zakrzewski, W. J.

    2005-01-01

    A simple phenomenological model for describing the conformational dynamics of biological macromolecules via the nonlinearity-induced instabilities is proposed. It is shown that the interaction between charges and bending degrees of freedom of closed molecular aggregates may act as drivers giving impetus to conformational dynamics of biopolymers. It is demonstrated that initially circular aggregates may undergo transformation to polygonal shapes and possible application to aggregates of bacter...

  5. Conformal Janus on Euclidean Sphere

    CERN Document Server

    Bak, Dongsu; Rey, Soo-Jong

    2016-01-01

    We interpret Janus as an interface in a conformal field theory and study its properties. The Janus is created by an exactly marginal operator and we study its effect on the interface conformal field theory on the Janus. We do this by utilizing the AdS/CFT correspondence. We compute the interface free energy both from leading correction to the Euclidean action in the dual gravity description and from conformal perturbation theory in the conformal field theory. We find that the two results agree each other and that the interface free energy scales precisely as expected from the conformal invariance of the Janus interface.

  6. Vibrational spectroscopic studies, Fukui functions, HOMO-LUMO, NLO, NBO analysis and molecular docking study of (E)-1-(1,3-benzodioxol-5-yl)-4,4-dimethylpent-1-en-3-one, a potential precursor to bioactive agents

    Science.gov (United States)

    Al-Wabli, Reem I.; Resmi, K. S.; Sheena Mary, Y.; Yohannan Panicker, C.; Attia, Mohamed I.; El-Emam, Ali A.; Van Alsenoy, C.

    2016-11-01

    The FT-IR and FT-Raman spectra of (E)-1-(1,3-benzodioxol-5-yl)-4,4-dimethylpent-1-en-3-one were recorded and analyzed experimentally and theoretically. The observed experimental and theoretical wavenumbers were assigned using potential energy distribution. The NLO properties were evaluated by the determination of first and second hyperpolarizabilities of the title compound. From the frontier molecular orbital study, the HOMO centers over the entire molecule except the methyl groups, while the LUMO is over the entire molecule except the CH2 group with the dioxole ring and one of the methyl groups. From the MEP plot, it is evident that the negative region covers the carbonyl and Cdbnd C groups and the positive region is over CH2 groups. The Fukui functions are also reported. The calculated geometrical parameters are in agreement with the XRD results. From the molecular docking study, the docked ligand title compound forms a stable complex with the androgen receptor and gives a binding affinity value of -8.1 kcal/mol and the results suggest that the compound might exhibit inhibitory activity against androgen receptor.

  7. Conformal superalgebras via tractor calculus

    Science.gov (United States)

    Lischewski, Andree

    2015-01-01

    We use the manifestly conformally invariant description of a Lorentzian conformal structure in terms of a parabolic Cartan geometry in order to introduce a superalgebra structure on the space of twistor spinors and normal conformal vector fields formulated in purely algebraic terms on parallel sections in tractor bundles. Via a fixed metric in the conformal class, one reproduces a conformal superalgebra structure that has been considered in the literature before. The tractor approach, however, makes clear that the failure of this object to be a Lie superalgebra in certain cases is due to purely algebraic identities on the spinor module and to special properties of the conformal holonomy representation. Moreover, it naturally generalizes to higher signatures. This yields new formulas for constructing new twistor spinors and higher order normal conformal Killing forms out of existing ones, generalizing the well-known spinorial Lie derivative. Moreover, we derive restrictions on the possible dimension of the space of twistor spinors in any metric signature.

  8. Conformal superalgebras via tractor calculus

    International Nuclear Information System (INIS)

    We use the manifestly conformally invariant description of a Lorentzian conformal structure in terms of a parabolic Cartan geometry in order to introduce a superalgebra structure on the space of twistor spinors and normal conformal vector fields formulated in purely algebraic terms on parallel sections in tractor bundles. Via a fixed metric in the conformal class, one reproduces a conformal superalgebra structure that has been considered in the literature before. The tractor approach, however, makes clear that the failure of this object to be a Lie superalgebra in certain cases is due to purely algebraic identities on the spinor module and to special properties of the conformal holonomy representation. Moreover, it naturally generalizes to higher signatures. This yields new formulas for constructing new twistor spinors and higher order normal conformal Killing forms out of existing ones, generalizing the well-known spinorial Lie derivative. Moreover, we derive restrictions on the possible dimension of the space of twistor spinors in any metric signature. (paper)

  9. Bioactive furanonaphthoquinones from Crescentia cujete.

    Science.gov (United States)

    Hetzel, C E; Gunatilaka, A A; Glass, T E; Kingston, D G; Hoffmann, G; Johnson, R K

    1993-09-01

    Bioassay-directed fractionation of the MeCOEt extract of Crescentia cujete (Bignonaceae) resulted in the isolation of (2S,3S)-3-hydroxy-5,6-dimethoxydehydroiso-alpha-lapachone [1], (2R)-5,6-dimethoxydehydroiso-alpha-lapachone [2], (2R)-5-methoxydehydroiso-alpha-lapachone [3], 2-(1-hydroxyethyl)naphtho[2,3-b]furan-4,9-dione [4], 5-hydroxy-2-(1-hydroxyethyl)naphtho[2,3-b]furan-4,9-dione [5], 2-isopropenylnaphtho[2,3-b]furan-4,9-dione [6], and 5-hydroxydehydroiso-alpha-lapachone [7]. Compounds 1-3 are new, and all compounds are bioactive, showing selective activity towards DNA-repair-deficient yeast mutants. The isolation, structure elucidation, and biological activities of these compounds are reported. PMID:8254347

  10. Leaf growth is conformal

    Science.gov (United States)

    Alim, Karen; Armon, Shahaf; Shraiman, Boris I.; Boudaoud, Arezki

    2016-10-01

    Growth pattern dynamics lie at the heart of morphogenesis. Here, we investigate the growth of plant leaves. We compute the conformal transformation that maps the contour of a leaf at a given stage onto the contour of the same leaf at a later stage. Based on the mapping we predict the local displacement field in the leaf blade and find it to agree with the experimentally measured displacement field to 92%. This approach is applicable to any two-dimensional system with locally isotropic growth, enabling the deduction of the whole growth field just from observation of the tissue contour.

  11. Conformance and Deviance

    DEFF Research Database (Denmark)

    Gjerdrum Pedersen, Esben Rahbek; Neergaard, Peter; Thusgaard Pedersen, Janni;

    2013-01-01

    This paper analyses how large Danish companies are responding to new governmental regulation which requires them to report on corporate social responsibility (CSR). The paper is based on an analysis of 142 company annual reports required by the new Danish regulation regarding CSR reporting, plus ...... in CSR reporting practices. Finally, it is argued that non-conformance with the new regulatory requirements is not solely about conscious resistance but may also be caused by, for example, lack of awareness, resource limitations, misinterpretations, and practical difficulties....

  12. New molecular scaffolds for the design of Mycobacterium tuberculosis type II dehydroquinase inhibitors identified using ligand and receptor based virtual screening.

    Science.gov (United States)

    Kumar, Ashutosh; Siddiqi, Mohammad Imran; Miertus, Stanislav

    2010-04-01

    Using ligand and receptor based virtual screening approaches we have identified potential virtual screening hits targeting type II dehydroquinase from Mycobacterium tuberculosis, an effective and validated anti-mycobacterial target. Initially, we applied a virtual screening workflow based on a combination of 2D structural fingerprints, 3D pharmacophore and molecular docking to identify compounds that rigidly match specific aspects of ligand bioactive conformation. Subsequently, the resulting compounds were ranked and prioritized using receptor interaction fingerprint based scoring and quantitative structure activity relationship model developed using already known actives. The virtual screening hits prioritized belong to several classes of molecular scaffolds with several available substitution positions that could allow chemical modification to enhance binding affinity. Finally, identified hits may be useful to a medicinal chemist or combinatorial chemist to pick up the new molecular starting points for medicinal chemistry optimization for the design of novel type II dehydroquinase inhibitors. PMID:19816720

  13. Kinetic analysis of hyaluronidase activity using a bioactive MRI contrast agent

    OpenAIRE

    Shiftan, Liora; Neeman, Michal

    2006-01-01

    One of the attractions of molecular imaging using ‘smart’ bioactive contrast agents is the ability to provide non-invasive data on the spatial and temporal changes in the distribution and expression patterns of specific enzymes. The tools developed for that aim could potentially also be developed for functional imaging of enzyme activity itself, through quantitative analysis of the rapid dynamics of enzymatic conversion of these contrast agents. High molecular weight hyaluronan, the natural s...

  14. Bioactivities and Health Benefits of Wild Fruits

    Directory of Open Access Journals (Sweden)

    Ya Li

    2016-08-01

    Full Text Available Wild fruits are exotic or underutilized. Wild fruits contain many bioactive compounds, such as anthocyanins and flavonoids. Many studies have shown that wild fruits possess various bioactivities and health benefits, such as free radical scavenging, antioxidant, anti-inflammatory, antimicrobial, and anticancer activity. Therefore, wild fruits have the potential to be developed into functional foods or pharmaceuticals to prevent and treat several chronic diseases. In the present article, we review current knowledge about the bioactivities and health benefits of wild fruits, which is valuable for the exploitation and utilization of wild fruits.

  15. Bioactivities and Health Benefits of Wild Fruits.

    Science.gov (United States)

    Li, Ya; Zhang, Jiao-Jiao; Xu, Dong-Ping; Zhou, Tong; Zhou, Yue; Li, Sha; Li, Hua-Bin

    2016-08-04

    Wild fruits are exotic or underutilized. Wild fruits contain many bioactive compounds, such as anthocyanins and flavonoids. Many studies have shown that wild fruits possess various bioactivities and health benefits, such as free radical scavenging, antioxidant, anti-inflammatory, antimicrobial, and anticancer activity. Therefore, wild fruits have the potential to be developed into functional foods or pharmaceuticals to prevent and treat several chronic diseases. In the present article, we review current knowledge about the bioactivities and health benefits of wild fruits, which is valuable for the exploitation and utilization of wild fruits.

  16. Bioactivities and Health Benefits of Wild Fruits.

    Science.gov (United States)

    Li, Ya; Zhang, Jiao-Jiao; Xu, Dong-Ping; Zhou, Tong; Zhou, Yue; Li, Sha; Li, Hua-Bin

    2016-01-01

    Wild fruits are exotic or underutilized. Wild fruits contain many bioactive compounds, such as anthocyanins and flavonoids. Many studies have shown that wild fruits possess various bioactivities and health benefits, such as free radical scavenging, antioxidant, anti-inflammatory, antimicrobial, and anticancer activity. Therefore, wild fruits have the potential to be developed into functional foods or pharmaceuticals to prevent and treat several chronic diseases. In the present article, we review current knowledge about the bioactivities and health benefits of wild fruits, which is valuable for the exploitation and utilization of wild fruits. PMID:27527154

  17. Conformally symmetric traversable wormholes

    International Nuclear Information System (INIS)

    Exact solutions of traversable wormholes are found under the assumption of spherical symmetry and the existence of a nonstatic conformal symmetry, which presents a more systematic approach in searching for exact wormhole solutions. In this work, a wide variety of solutions are deduced by considering choices for the form function, a specific linear equation of state relating the energy density and the pressure anisotropy, and various phantom wormhole geometries are explored. A large class of solutions impose that the spatial distribution of the exotic matter is restricted to the throat neighborhood, with a cutoff of the stress-energy tensor at a finite junction interface, although asymptotically flat exact solutions are also found. Using the 'volume integral quantifier', it is found that the conformally symmetric phantom wormhole geometries may, in principle, be constructed by infinitesimally small amounts of averaged null energy condition violating matter. Considering the tidal acceleration traversability conditions for the phantom wormhole geometry, specific wormhole dimensions and the traversal velocity are also deduced

  18. NMR-based, molecular dynamics- and random walk molecular mechanics-supported study of conformational aspects of a carbohydrate ligand (Galβ1-2Galβ1-R) for an animal galectin in the free and in the bound state

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Siebert, H.-C; Gilleron, M.; Kaltner, H.; Lieth, C.-W. von der; Kozár, T.; Bovin, N.; Korchagina, E.Y.

    1996-01-01

    The binding of a carbohydrate to a lectin may affect the conformation of the ligand. To address this question for the galectin from chicken liver, the conformation of Gal@b1-R was analyzed in the free and in the galectin-bound state with 2D-ROESY- and 1D- as well as 2D-transferred NOE-experiments. A

  19. Bioactivity of bioresorbable composite based on bioactive glass and poly-L-lactide

    Institute of Scientific and Technical Information of China (English)

    ZHOU Zhi-hua; RUAN Jian-ming; ZOU Jian-peng; ZHOU Zhong-cheng; SHEN Xiong-jun

    2007-01-01

    Bioactive and bioresorbable composite was fabricated by a solvent evaporation technique using poly-L-lactide(PLLA) and bioactive glass (average particle size: 6.8 μm). Bioactive glass granules are homogeneously distributed in the composite with microcrack structure. The formation of hydroxyapatite(HA) on the composite in simulated body fluid(SBF) was analyzed by scanning electron microscopy(SEM), energy dispersive spectroscopy(EDS), X-ray diffraction(XRD), and Raman spectra. Rod-like HA crystals deposit on the surface of PLLA/bioactive glass composite after soaking for 3 d. Both rod-like crystals and HA layer form on the surface for 14 d in SBF. The high bioactivity of PLLA/bioactive glass composite indicates the potential of materials for integration with bone.

  20. Bioactive Carbohydrates and Peptides in Foods: An Overview of Sources, Downstream Processing Steps and Associated Bioactivities.

    Science.gov (United States)

    Hayes, Maria; Tiwari, Brijesh K

    2015-01-01

    Bioactive peptides and carbohydrates are sourced from a myriad of plant, animal and insects and have huge potential for use as food ingredients and pharmaceuticals. However, downstream processing bottlenecks hinder the potential use of these natural bioactive compounds and add cost to production processes. This review discusses the health benefits and bioactivities associated with peptides and carbohydrates of natural origin and downstream processing methodologies and novel processes which may be used to overcome these.

  1. Design and characterization of protein-quercetin bioactive nanoparticles

    Directory of Open Access Journals (Sweden)

    Leng Xiaojing

    2011-05-01

    Full Text Available Abstract Background The synthesis of bioactive nanoparticles with precise molecular level control is a major challenge in bionanotechnology. Understanding the nature of the interactions between the active components and transport biomaterials is thus essential for the rational formulation of bio-nanocarriers. The current study presents a single molecule of bovine serum albumin (BSA, lysozyme (Lys, or myoglobin (Mb used to load hydrophobic drugs such as quercetin (Q and other flavonoids. Results Induced by dimethyl sulfoxide (DMSO, BSA, Lys, and Mb formed spherical nanocarriers with sizes less than 70 nm. After loading Q, the size was further reduced by 30%. The adsorption of Q on protein is mainly hydrophobic, and is related to the synergy of Trp residues with the molecular environment of the proteins. Seven Q molecules could be entrapped by one Lys molecule, 9 by one Mb, and 11 by one BSA. The controlled releasing measurements indicate that these bioactive nanoparticles have long-term antioxidant protection effects on the activity of Q in both acidic and neutral conditions. The antioxidant activity evaluation indicates that the activity of Q is not hindered by the formation of protein nanoparticles. Other flavonoids, such as kaempferol and rutin, were also investigated. Conclusions BSA exhibits the most remarkable abilities of loading, controlled release, and antioxidant protection of active drugs, indicating that such type of bionanoparticles is very promising in the field of bionanotechnology.

  2. Structure, dynamics, and surface reactions of bioactive glasses

    Science.gov (United States)

    Zeitler, Todd R.

    Three bioactive glasses (45S5, 55S4.3, and 60S3.8) have been investigated using atomic-scale molecular dynamics simulations in attempt to explain differences in observed macroscopic bioactivity. Bulk and surface structures and bulk dynamics have been characterized. Ion exchange and hydrolysis reactions, the first two stages in Hench's model describing the reactions of bioactive glass surfaces in vivo, have been investigated in detail. The 45S5 composition shows a much greater network fragmentation: it is suggested that this fragmentation can play a role in at least the first two stages of Hench's model for HCA formation on the surfaces of bioactive glasses. In terms of dynamic behavior, long-range diffusion was only observed for sodium. Calcium showed only jumps between adjacent sites, while phosphorus showed only local vibrations. Surface simulations show the distinct accumulation of sodium at the immediate surface for each composition. Surface channels are also shown to exist and are most evident for 45S5 glass. Results for a single ion exchange showed that the ion-exchange reaction is preferred (more exothermic) for Na+ ions near Si, rather than P. A range of reaction energies were found, due to a range of local environments, as expected for a glass surface. The average reaction energies are not significantly different among the three glass compositions. The results for bond hydrolysis on as-created surfaces show no significant differences among the three compositions for simulations involving Si-O-Si or Si-O-P. All average values are greater than zero, indicating endothermic reactions that are not favorable by themselves. However, it is shown that the hydrolysis reactions became more favorable (in fact, exothermic for 45S5 and 55S4.3) when simulated on surfaces that had already been ion-exchanged. This is significant because it gives evidence supporting Hench's proposed reaction sequence. Perhaps even more significantly, the reaction energies for hydrolysis

  3. Molecular Mechanics

    OpenAIRE

    Vanommeslaeghe, Kenno; Guvench, Olgun; Alexander D MacKerell

    2014-01-01

    Molecular Mechanics (MM) force fields are the methods of choice for protein simulations, which are essential in the study of conformational flexibility. Given the importance of protein flexibility in drug binding, MM is involved in most if not all Computational Structure-Based Drug Discovery (CSBDD) projects. This section introduces the reader to the fundamentals of MM, with a special emphasis on how the target data used in the parametrization of force fields determine their strengths and wea...

  4. Structural reassignment, absolute configuration, and conformation of hypurticin, a highly flexible polyacyloxy-6-heptenyl-5,6-dihydro-2H-pyran-2-one.

    Science.gov (United States)

    Mendoza-Espinoza, José Alberto; López-Vallejo, Fabian; Fragoso-Serrano, Mabel; Pereda-Miranda, Rogelio; Cerda-García-Rojas, Carlos M

    2009-04-01

    The structural reassignment, absolute configuration, and conformational behavior of the highly flexible natural product hypurticin (pectinolide E), 6S-[3'S,5'R,6'S-triacetoxy-1Z-heptenyl]-5S-acetoxy-5,6-dihydro-2H-pyran-2-one (1), were ascertained by a molecular modeling protocol, which includes extensive conformational searching, geometry optimization by DFT B3LYP/DGDZVP calculations, and comparison between the theoretical (DFT) and experimental (1)H-(1)H NMR coupling constants. Hyptolide (2), a related cytotoxic 5,6-dihydro-2H-pyran-2-one that increased the S phase of the HeLa cell cycle, was employed as a reference substance to validate the theoretical protocol designed to characterize the 3D properties of compound 1. The related synthetic derivative, tri-O-acetyl-3,6-dideoxy-d-glucose diphenyldithioacetal (14), was prepared by a six-step reaction sequence starting from d-glucose and served as an enantiopure building block to reinforce the structural and configurational assignment of 1. This protocol proved to be an important tool for the structural characterization of highly flexible bioactive polyoxygenated natural products. PMID:19265396

  5. Fermion-Scalar Conformal Blocks

    CERN Document Server

    Iliesiu, Luca; Poland, David; Pufu, Silviu S; Simmons-Duffin, David; Yacoby, Ran

    2015-01-01

    We compute the conformal blocks associated with scalar-scalar-fermion-fermion 4-point functions in 3D CFTs. Together with the known scalar conformal blocks, our result completes the task of determining the so-called `seed blocks' in three dimensions. Conformal blocks associated with 4-point functions of operators with arbitrary spins can now be determined from these seed blocks by using known differential operators.

  6. Subtleties Concerning Conformal Tractor Bundles

    CERN Document Server

    Graham, C Robin

    2012-01-01

    The realization of tractor bundles as associated bundles in conformal geometry is studied. It is shown that different natural choices of principal bundle with normal Cartan connection corresponding to a given conformal manifold can give rise to topologically distinct associated tractor bundles for the same inducing representation. Consequences for homogeneous models and conformal holonomy are described. A careful presentation is made of background material concerning standard tractor bundles and equivalence between parabolic geometries and underlying structures.

  7. Einstein Gravity from Conformal Gravity

    OpenAIRE

    Maldacena, Juan

    2011-01-01

    We show that that four dimensional conformal gravity plus a simple Neumann boundary condition can be used to get the semiclassical (or tree level) wavefunction of the universe of four dimensional asymptotically de-Sitter or Euclidean anti-de Sitter spacetimes. This simple Neumann boundary condition selects the Einstein solution out of the more numerous solutions of conformal gravity. It thus removes the ghosts of conformal gravity from this computation. In the case of a five dimensional pure ...

  8. Coends in conformal field theory

    CERN Document Server

    Fuchs, Jürgen

    2016-01-01

    The idea of "summing over all intermediate states" that is central for implementing locality in quantum systems can be realized by coend constructions. In the concrete case of systems of conformal blocks for a certain class of conformal vertex algebras, one deals with coends in functor categories. Working with these coends involves quite a few subtleties which, even though they have in principle already been understood twenty years ago, have not been sufficiently appreciated by the conformal field theory community.

  9. Dimensional Reduction for Conformal Blocks

    CERN Document Server

    Hogervorst, Matthijs

    2016-01-01

    We consider the dimensional reduction of a CFT, breaking multiplets of the d-dimensional conformal group SO(d+1,1) up into multiplets of SO(d,1). This leads to an expansion of d-dimensional conformal blocks in terms of blocks in d-1 dimensions. In particular, we obtain a formula for 3d conformal blocks as an infinite sum over 2F1 hypergeometric functions with closed-form coefficients.

  10. Surface signatures of bioactivity: MD simulations of 45S and 65S silicate glasses.

    Science.gov (United States)

    Tilocca, Antonio; Cormack, Alastair N

    2010-01-01

    The surface of a bioactive (45S) and a bioinactive (65S) glass composition has been modeled using shell-model classical molecular dynamics simulations. Direct comparison of the two structures allowed us to identify the potential role of specific surface features in the processes leading to integration of a bioglass implant with the host tissues, focusing in particular on the initial dissolution of the glass network. The simulations highlight the critical role of network fragmentation and sodium enrichment of the surface in determining the rapid hydrolysis and release of silica fragments in solution, characteristic of highly bioactive compositions. On the other hand, no correlation has been found between the surface density of small (two- and three-membered) rings and bioactivity, thus suggesting that additional factors need to be taken into account to fully understand the role of these sites in the mechanism leading to calcium phosphate deposition on the glass surface. PMID:19725567

  11. Going viral: designing bioactive surfaces with bacteriophage.

    Science.gov (United States)

    Hosseinidoust, Zeinab; Olsson, Adam L J; Tufenkji, Nathalie

    2014-12-01

    Bacteriophage-functionalized bioactive surfaces are functional materials that can be used as antimicrobial surfaces in medical applications (e.g., indwelling medical devices or wound dressings) or as biosensors for bacterial capture and detection. Despite offering immense potential, designing efficient phage-functionalized bioactive surfaces is hampered by a number of challenges. This review offers an overview of the current state of knowledge in this field and presents a critical perspective of the technological promises and challenges.

  12. Release of bioactive active iodine in kelp

    Institute of Scientific and Technical Information of China (English)

    SUN Xiang-wu; WENG Huan-xin; QIN Ya-chao

    2005-01-01

    The release process and influencing factors of bioactive iodine of kelp are systemically studied by leaching experiment. The results showed that the bioactive iodine of kelp can be released rapidly and the principal form of iodine in lixivium is I- . There is a dynamic process between the release and absorption of iodine. With the increase of leaching water, the gross amounts of released iodine rise.There also exists a transforming process among I- , IO3- and organic iodine in lixivium.

  13. Microencapsulation of bioactives for food applications

    OpenAIRE

    Dias, Maria Inês; Isabel C. F. R. Ferreira; Barreiro, M.F.

    2015-01-01

    Health issues are an emerging concern to the world population, and therefore the food industry is searching for novel food products containing health-promoting bioactive compounds, with little or no synthetic ingredients. However, there are some challenges in the development of functional foods, particularly in which the direct use of some bioactives is involved. They can show problems of instability, react with other food matrix ingredients or present strong odour and/or flavours. In this co...

  14. Reflections on Conformal Spectra

    CERN Document Server

    Kim, Hyungrok; Ooguri, Hirosi

    2015-01-01

    We use modular invariance and crossing symmetry of conformal field theory to reveal approximate reflection symmetries in the spectral decompositions of the partition function in two dimensions in the limit of large central charge and of the four-point function in any dimension in the limit of large scaling dimensions $\\Delta_0$ of external operators. We use these symmetries to motivate universal upper bounds on the spectrum and the operator product expansion coefficients, which we then derive by independent techniques. Some of the bounds for four-point functions are valid for finite $\\Delta_0$ as well as for large $\\Delta_0$. We discuss a similar symmetry in a large spacetime dimension limit. Finally, we comment on the analogue of the Cardy formula and sparse light spectrum condition for the four-point function.

  15. Reflections on Conformal Spectra

    CERN Document Server

    CERN. Geneva

    2015-01-01

    We use modular invariance and crossing symmetry of conformal field theory to reveal approximate reflection symmetries in the spectral decompositions of the partition function in two dimensions in the limit of large central charge and of the four-point function in any dimension in the limit of large scaling dimensions Δ0 of external operators. We use these symmetries to motivate universal upper bounds on the spectrum and the operator product expansion coefficients, which we then derive by independent techniques. Some of the bounds for four-point functions are valid for finite Δ0 as well as for large Δ0. We discuss a similar symmetry in a large spacetime dimension limit. Finally, we comment on the analogue of the Cardy formula and sparse light spectrum condition for the four-point function. (based on 1510.08772 with Kim & Ooguri). This seminar will be given via videolink

  16. Conformal Spectrum and Harmonic maps

    CERN Document Server

    Nadirashvili, Nikolai

    2010-01-01

    This paper is devoted to the study of the conformal spectrum (and more precisely the first eigenvalue) of the Laplace-Beltrami operator on a smooth connected compact Riemannian surface without boundary, endowed with a conformal class. We give a constructive proof of a critical metric which is smooth except at some conical singularities and maximizes the first eigenvalue in the conformal class of the background metric. We also prove that the map associating a finite number of eigenvectors of the maximizing $\\lambda_1$ into the sphere is harmonic, establishing a link between conformal spectrum and harmonic maps.

  17. Loop Virasoro Lie conformal algebra

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Henan, E-mail: wuhenanby@163.com; Chen, Qiufan; Yue, Xiaoqing [Department of Mathematics, Tongji University, Shanghai 200092 (China)

    2014-01-15

    The Lie conformal algebra of loop Virasoro algebra, denoted by CW, is introduced in this paper. Explicitly, CW is a Lie conformal algebra with C[∂]-basis (L{sub i} | i∈Z) and λ-brackets [L{sub i} {sub λ} L{sub j}] = (−∂−2λ)L{sub i+j}. Then conformal derivations of CW are determined. Finally, rank one conformal modules and Z-graded free intermediate series modules over CW are classified.

  18. Correlated Flexible Molecular Coding and Molecular Evolvability

    OpenAIRE

    Husimi, Y; Aita, T.; Tabuchi, I.

    2002-01-01

    Evolvability of biopolymers is based on molecular coding. The molecular coding is represented by biopolymer function vs monomeric sequence relationship, that is, a proper fitness landscape on the sequence space. On the other hand, molecular coding is mostly realized by monomeric sequence vs biopolymer structure relationship. We suggest the evolution of evolvability based on flexible or multiplex coding originating from flexible or polymorphic conformation of evolving biopolymers. We report a ...

  19. Hydrogel/bioactive glass composites for bone regeneration applications: Synthesis and characterisation

    Energy Technology Data Exchange (ETDEWEB)

    Killion, John A., E-mail: jkillion@research.ait.ie [Materials Research Institute, Athlone Institute of Technology, Dublin Rd, Athlone, Co. Westmeath (Ireland); Kehoe, Sharon, E-mail: sh625116@dal.ca [Department of Applied Oral Sciences, Dalhousie University, Halifax, NS B3H 34R2 (Canada); Geever, Luke M., E-mail: lgeever@ait.ie [Materials Research Institute, Athlone Institute of Technology, Dublin Rd, Athlone, Co. Westmeath (Ireland); Devine, Declan M., E-mail: ddevine@ait.ie [Materials Research Institute, Athlone Institute of Technology, Dublin Rd, Athlone, Co. Westmeath (Ireland); Sheehan, Eoin, E-mail: eoinsheehan@aol.com [Department of Trauma and Orthopaedics, MRHT, Tullamore, Co. Offaly (Ireland); Boyd, Daniel, E-mail: d.boyd@dal.ca [Department of Applied Oral Sciences, Dalhousie University, Halifax, NS B3H 34R2 (Canada); Higginbotham, Clement L., E-mail: chigginbotham@ait.ie [Materials Research Institute, Athlone Institute of Technology, Dublin Rd, Athlone, Co. Westmeath (Ireland)

    2013-10-15

    Due to the deficiencies of current commercially available biological bone grafts, alternative bone graft substitutes have come to the forefront of tissue engineering in recent times. The main challenge for scientists in manufacturing bone graft substitutes is to obtain a scaffold that has sufficient mechanical strength and bioactive properties to promote formation of new tissue. The ability to synthesise hydrogel based composite scaffolds using photopolymerisation has been demonstrated in this study. The prepared hydrogel based composites were characterised using techniques including Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), Energy-dispersive X-ray spectrometry (EDX), rheological studies and compression testing. In addition, gel fraction, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), porosity and swelling studies of the composites were carried out. It was found that these novel hydrogel bioglass composite formulations did not display the inherent brittleness that is typically associated with bioactive glass based bone graft materials and exhibited enhanced biomechanical properties compared to the polyethylene glycol hydrogel scaffolds along. Together, the combination of enhanced mechanical properties and the deposition of apatite on the surface of these hydrogel based composites make them an ideal candidate as bone graft substitutes in cancellous bone defects or low load bearing applications. Highlights: • Young's modulus increases with the addition of bioactive glasses. • Hydrogel based composites formed an apatite layer in simulated body fluid. • Storage modulus increases with addition of bioactive glasses. • Compressive strength is dependent on molecular weight and bioactive glass loading.

  20. Neural network methods for identification and optimization of quantum mechanical features needed for bioactivity.

    Science.gov (United States)

    Braunheim, B B; Schwartz, S D

    2000-09-01

    This paper presents a new approach to the discovery and design of bioactive compounds. The focus of this application will be on the analysis of enzymatic inhibitors. At present the discovery of enzymatic inhibitors for therapeutic use is often accomplished through random searches. The first phase of discovery is a random search through a large pre-fabricated chemical library. Many molecules are tested with refined enzyme for signs of inhibition. Once a group of lead compounds have been discovered the chemical intuition of biochemists is used to find structurally related compounds that are more effective. This step requires new molecules to be conceived and synthesized, and it is the most time-consuming and expensive step. The development of computational and theoretical methods for prediction of the molecular structure that would bind most tightly prior to synthesis and testing, would facilitate the design of novel inhibitors. In the past, our work has focused on solving the problem of predicting the bioactivity of a molecule prior to synthesis. We used a neural network trained with the bioactivity of known compounds to predict the bioactivity of unknown compounds. In our current work, we use a separate neural network in conjunction with a trained neural network in an attempt to gain insight as to how to modify existing compounds and increase their bioactivity.

  1. Design, synthesis, α-glucosidase inhibitory activity, molecular docking and QSAR studies of benzimidazole derivatives

    Science.gov (United States)

    Dinparast, Leila; Valizadeh, Hassan; Bahadori, Mir Babak; Soltani, Somaieh; Asghari, Behvar; Rashidi, Mohammad-Reza

    2016-06-01

    In this study the green, one-pot, solvent-free and selective synthesis of benzimidazole derivatives is reported. The reactions were catalyzed by ZnO/MgO containing ZnO nanoparticles as a highly effective, non-toxic and environmentally friendly catalyst. The structure of synthesized benzimidazoles was characterized using spectroscopic technics (FT-IR, 1HNMR, 13CNMR). Synthesized compounds were evaluated for their α-glucosidase inhibitory potential. Compounds 3c, 3e, 3l and 4n were potent inhibitors with IC50 values ranging from 60.7 to 168.4 μM. In silico studies were performed to explore the binding modes and interactions between enzyme and synthesized benzimidazoles. Developed linear QSAR model based on density and molecular weight could predict bioactivity of newly synthesized compounds well. Molecular docking studies revealed the availability of some hydrophobic interactions. In addition, the bioactivity of most potent compounds had good correlation with estimated free energy of binding (ΔGbinding) which was calculated according to docked best conformations.

  2. Replacement between conformity and counter-conformity in consumption decisions.

    Science.gov (United States)

    Chou, Ting-Jui; Chang, En-Chung; Dai, Qi; Wong, Veronica

    2013-02-01

    This study assessed, in a Chinese context, how self-esteem interacts with perceived similarity and uniqueness to yield cognitive dissonance, and whether the dissonance leads to self-reported conformity or counter-conformity behavior. Participants were 408 respondents from 4 major Chinese cities (M age = 33.0 yr., SD = 4.3; 48% men). Self-perceptions of uniqueness, similarity, cognitive dissonance, self-esteem and need to behave in conformity or counter-conformity were measured. A theoretical model was assessed in four situations, relating the ratings of self-esteem and perceived similarity/uniqueness to the way other people at a wedding were dressed, and the resultant cognitive dissonance and conformity/ counter-conformity behavior. Regardless of high or low self-esteem, all participants reported cognitive dissonance when they were told that they were dressed extremely similarly to or extremely differently from the other people attending the wedding. However, the conforming/counter-conforming strategies used by participants to resolve the cognitive dissonance differed. When encountering dissonance induced by the perceived extreme uniqueness of dress, participants with low self-esteem tended to say they would dress next time so as to conform with the way others were dressed, while those with high self-esteem indicated they would continue their counter-conformity in attire. When encountering dissonance induced by the perceived extreme similarity to others, both those with high and low self-esteem tended to say they would dress in an unorthodox manner to surprise other people in the future. PMID:23654033

  3. Replacement between conformity and counter-conformity in consumption decisions.

    Science.gov (United States)

    Chou, Ting-Jui; Chang, En-Chung; Dai, Qi; Wong, Veronica

    2013-02-01

    This study assessed, in a Chinese context, how self-esteem interacts with perceived similarity and uniqueness to yield cognitive dissonance, and whether the dissonance leads to self-reported conformity or counter-conformity behavior. Participants were 408 respondents from 4 major Chinese cities (M age = 33.0 yr., SD = 4.3; 48% men). Self-perceptions of uniqueness, similarity, cognitive dissonance, self-esteem and need to behave in conformity or counter-conformity were measured. A theoretical model was assessed in four situations, relating the ratings of self-esteem and perceived similarity/uniqueness to the way other people at a wedding were dressed, and the resultant cognitive dissonance and conformity/ counter-conformity behavior. Regardless of high or low self-esteem, all participants reported cognitive dissonance when they were told that they were dressed extremely similarly to or extremely differently from the other people attending the wedding. However, the conforming/counter-conforming strategies used by participants to resolve the cognitive dissonance differed. When encountering dissonance induced by the perceived extreme uniqueness of dress, participants with low self-esteem tended to say they would dress next time so as to conform with the way others were dressed, while those with high self-esteem indicated they would continue their counter-conformity in attire. When encountering dissonance induced by the perceived extreme similarity to others, both those with high and low self-esteem tended to say they would dress in an unorthodox manner to surprise other people in the future.

  4. Conformation of α,α,α'-Trisubstituted Cyclododecanone

    Institute of Scientific and Technical Information of China (English)

    WANG,Ming-An; ZHANG,Ning; LU,Hui-Zhe; WANG,Dao-Quan

    2007-01-01

    Ten α,α,α'-trisubstituted cyclododecanones were synthesized and characterized by elemental analyses, infrared,1H NMR and 13C NMR spectra, and X-ray diffraction. NMR data could not give conformational information clearly,but some of their ring skeleton conformations of cyclododecanone moiety were showed to remain the unchanged [3333]-2-one conformation with little distortion, while the others were changed to the [3324]-2-one conformation in their crystal structures. These are consistent with the results of molecular mechanics calculation with Sybyl 6.9 software and Tripos force field, and semi-empirical quantum calculation with AM1 method in Gaussian 98 software.Two geminal substituting groups are located at α-comer carbon atom, and the third group is at α-side-exo carbon atom in both conformations. Both [3333]-2-one and [3324]-2-one conformations are present in a dynamic equilibrium in the solution, but only one preferred conformation exists in the crystal solid.

  5. Distal histidine conformational flexibility in dehaloperoxidase from Amphitrite ornata

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zuxu; de Serrano, Vesna; Betts, Laurie; Franzen, Stefan; (NCSU); (UNC)

    2009-01-28

    The enzyme dehaloperoxidase (DHP) from the terebellid polychaete Amphitrite ornata is a heme protein which has a globin fold but can function as both a hemoglobin and a peroxidase. As a peroxidase, DHP is capable of converting 2,4,6-trihalophenols to the corresponding 2,6-dihaloquinones in the presence of hydrogen peroxide. As a hemoglobin, DHP cycles between the oxy and deoxy states as it reversibly binds oxygen for storage. Here, it is reported that the distal histidine, His55, exhibits conformational flexibility in the deoxy form and is consequently observed in two solvent-exposed conformations more than 9.5 {angstrom} away from the heme. These conformations are analogous to the open conformation of sperm whale myoglobin. The heme iron in deoxy ferrous DHP is five-coordinate and has an out-of-plane displacement of 0.25 {angstrom} from the heme plane. The observation of five-coordinate heme iron with His55 in a remote solvent-exposed conformation is consistent with the hypothesis that His55 interacts with heme iron ligands through hydrogen bonding in the closed conformation. Since His55 is also displaced by the binding of 4-iodophenol in an internal pocket, these results provide new insight into the correlation between heme iron ligation, molecular binding in the distal pocket and the conformation of the distal histidine in DHP.

  6. Conformational Study of Taurine in the Gas Phase

    Science.gov (United States)

    Cortijo, Vanessa; Sanz, M. Eugenia; López, Juan C.; Alonso, José L.

    2009-08-01

    The conformational preferences of the amino sulfonic acid taurine (NH2-CH2-CH2-SO3H) have been investigated in the gas phase by laser ablation molecular beam Fourier transform microwave spectroscopy (LA-MB-FTMW) in the 6-14 GHz frequency range. One conformer has been observed, and its rotational, centrifugal distortion, and hyperfine quadrupole coupling constants have been determined from the analysis of its rotational spectrum. Comparison of the experimental constants with those calculated theoretically identifies the detected conformer unambiguously. The observed conformer of taurine is stabilized by an intramolecular hydrogen bond O-H···N between the hydrogen of the sulfonic acid group and the nitrogen atom of the amino group.

  7. In silico Exploration of the Conformational Universe of GPCRs.

    Science.gov (United States)

    Rodríguez-Espigares, Ismael; Kaczor, Agnieszka A; Selent, Jana

    2016-07-01

    The structural plasticity of G protein coupled receptors (GPCRs) leads to a conformational universe going from inactive to active receptor states with several intermediate states. Many of them have not been captured yet and their role for GPCR activation is not well understood. The study of this conformational space and the transition dynamics between different receptor populations is a major challenge in molecular biophysics. The rational design of effector molecules that target such receptor populations allows fine-tuning receptor signalling with higher specificity to produce drugs with safer therapeutic profiles. In this minireview, we outline highly conserved receptor regions which are considered determinant for the establishment of distinct receptor states. We then discuss in-silico approaches such as dimensionality reduction methods and Markov State Models to explore the GPCR conformational universe and exploit the obtained conformations through structure-based drug design.

  8. In silico Exploration of the Conformational Universe of GPCRs.

    Science.gov (United States)

    Rodríguez-Espigares, Ismael; Kaczor, Agnieszka A; Selent, Jana

    2016-07-01

    The structural plasticity of G protein coupled receptors (GPCRs) leads to a conformational universe going from inactive to active receptor states with several intermediate states. Many of them have not been captured yet and their role for GPCR activation is not well understood. The study of this conformational space and the transition dynamics between different receptor populations is a major challenge in molecular biophysics. The rational design of effector molecules that target such receptor populations allows fine-tuning receptor signalling with higher specificity to produce drugs with safer therapeutic profiles. In this minireview, we outline highly conserved receptor regions which are considered determinant for the establishment of distinct receptor states. We then discuss in-silico approaches such as dimensionality reduction methods and Markov State Models to explore the GPCR conformational universe and exploit the obtained conformations through structure-based drug design. PMID:27492237

  9. Microtubule's conformational cap

    DEFF Research Database (Denmark)

    Chretien, D.; Janosi, I.; Taveau, J.C.;

    1999-01-01

    The molecular mechanisms that allow elongation of the unstable microtubule lattice remain unclear. It is usually thought that the GDP-liganded tubulin lattice is capped by a small layer of GTP- or GDP-P(i)-liganded molecules, the so called "GTP-cap". Here, we point-out that the elastic properties...

  10. Counselor Identity: Conformity or Distinction?

    Science.gov (United States)

    McLaughlin, Jerry E.; Boettcher, Kathryn

    2009-01-01

    The authors explore 3 debates in other disciplines similar to counseling's identity debate in order to learn about common themes and outcomes. Conformity, distinction, and cohesion emerged as common themes. They conclude that counselors should retain their distinctive, humanistic approach rather than conforming to the dominant, medical approach.

  11. Classical Virasoro irregular conformal block

    CERN Document Server

    Rim, Chaiho

    2015-01-01

    Virasoro irregular conformal block with arbitrary rank is obtained for the classical limit or equivalently Nekrasov-Shatashvili limit using the beta-deformed irregular matrix model (Penner-type matrix model for the irregular conformal block). The same result is derived using the generalized Mathieu equation which is equivalent to the loop equation of the irregular matrix model.

  12. Ras Conformational Ensembles, Allostery, and Signaling.

    Science.gov (United States)

    Lu, Shaoyong; Jang, Hyunbum; Muratcioglu, Serena; Gursoy, Attila; Keskin, Ozlem; Nussinov, Ruth; Zhang, Jian

    2016-06-01

    Ras proteins are classical members of small GTPases that function as molecular switches by alternating between inactive GDP-bound and active GTP-bound states. Ras activation is regulated by guanine nucleotide exchange factors that catalyze the exchange of GDP by GTP, and inactivation is terminated by GTPase-activating proteins that accelerate the intrinsic GTP hydrolysis rate by orders of magnitude. In this review, we focus on data that have accumulated over the past few years pertaining to the conformational ensembles and the allosteric regulation of Ras proteins and their interpretation from our conformational landscape standpoint. The Ras ensemble embodies all states, including the ligand-bound conformations, the activated (or inactivated) allosteric modulated states, post-translationally modified states, mutational states, transition states, and nonfunctional states serving as a reservoir for emerging functions. The ensemble is shifted by distinct mutational events, cofactors, post-translational modifications, and different membrane compositions. A better understanding of Ras biology can contribute to therapeutic strategies. PMID:26815308

  13. Initial conformation of kinesin's neck linker

    CERN Document Server

    Geng, Yi-Zhao; Liu, Shu-Xia; Yan, Shiwei

    2013-01-01

    How ATP binding initiates the docking process of kinesin's neck linker is a key question in understanding kinesin mechanism. It is believed that the formation of an extra turn structure by the first three amino acids of neck linker (LYS325, THR326, ILE327 in 2KIN) is crucial for initiating the docking process. But the initial conformation of neck linker (specially the three amino acids of the extra turn) and the neck linker docking initiation mechanism remain unclear. By using molecular dynamics method, we investigate the initial conformation of kinesin's neck linker in the docking process. We find that, in the initial state of NL docking process, NL still has interactions with {\\beta}0 and forms a conformation similar to the "cover-neck bundle" structure proposed by Hwang et al. [Structure 2008, 16(1): 62-71]. From this initial structure, the docking of the "cover-neck bundle" structure can be achieved. The motor head provides a forward force on the initial cover-neck bundle structure through ATP-induced rot...

  14. Towards conformal loop quantum gravity

    CERN Document Server

    Wang, C H T

    2006-01-01

    A discussion is given of recent developments in canonical gravity that assimilates the conformal analysis of gravitational degrees of freedom. The work is motivated by the problem of time in quantum gravity and is carried out at the metric and the triad levels. At the metric level, it is shown that by extending the Arnowitt-Deser-Misner (ADM) phase space of general relativity (GR), a conformal form of geometrodynamics can be constructed. In addition to the Hamiltonian and diffeomorphism constraints, an extra first class constraint is introduced to generate conformal transformations. This phase space consists of York's mean extrinsic curvature time, conformal three-metric and their momenta. At the triad level, the phase space of GR is further enlarged by incorporating spin-gauge as well as conformal symmetries. This leads to a canonical formulation of GR using a new set of real spin connection variables. The resulting gravitational constraints are first class, consisting of the Hamiltonian constraint and the c...

  15. Projectors, Shadows, and Conformal Blocks

    CERN Document Server

    Simmons-Duffin, David

    2012-01-01

    We introduce a method for computing conformal blocks of operators in arbitrary Lorentz representations in any spacetime dimension, making it possible to apply bootstrap techniques to operators with spin. The key idea is to implement the "shadow formalism" of Ferrara, Gatto, Grillo, and Parisi in a setting where conformal invariance is manifest. Conformal blocks in d-dimensions can be expressed as integrals over the projective null-cone in the "embedding space" R^{d+1,1}. Taking care with their analytic structure, these integrals can be evaluated in great generality, reducing the computation of conformal blocks to a bookkeeping exercise. To facilitate calculations in four-dimensional CFTs, we introduce techniques for writing down conformally-invariant correlators using auxiliary twistor variables, and demonstrate their use in some simple examples.

  16. Recursion Relations for Conformal Blocks

    CERN Document Server

    Penedones, João; Yamazaki, Masahito

    2015-01-01

    In the context of conformal field theories in general space-time dimension, we find all the possible singularities of the conformal blocks as functions of the scaling dimension $\\Delta$ of the exchanged operator. In particular, we argue, using representation theory of parabolic Verma modules, that in odd spacetime dimension the singularities are only simple poles. We discuss how to use this information to write recursion relations that determine the conformal blocks. We first recover the recursion relation introduced in 1307.6856 for conformal blocks of external scalar operators. We then generalize this recursion relation for the conformal blocks associated to the four point function of three scalar and one vector operator. Finally we specialize to the case in which the vector operator is a conserved current.

  17. Bioactivity of Rumex obtusifolius (Polygonaceae

    Directory of Open Access Journals (Sweden)

    Harshaw Diane

    2010-01-01

    Full Text Available Rumex obtusifolius L. (Polygonaceae, commonly known as 'broad-leaf dock', is one of the most common Irish wayside weeds, and it also occurs in silage fields, on river banks, in ditches and on waste grounds. The ethnobotanical uses of this species include its use as an antidote to nettle, depurative, astringent, laxative, and tonic, and in the treatment of sores, blisters, burns, cancer and tumors. The bioactivities of n-hexane, dichloromethane (DCM and methanol (MeOH extracts of the leaves of R. obtusifolius were assessed using the 2,2-Diphenyl-1-picrylhydrazyl (DPPH assay, the newly developed micro-titer-based antimicrobial assay incorporating resazurin as an indicator of cell growth, and the brine shrimp lethality assay. The most potent free radical scavenging activity was displayed by the MeOH extract with a RC50 value of 7.80 x 10-2 mg/mL. Among the fractions obtained from solid-phase extraction (SPE of the MeOH extract, the 50% aqueous methanolic SPE fraction exhibited the highest levels of free radical scavenging property (RC50 = 1.05 x 10-2 mg/mL. While the n-hexane extract did not show any antibacterial activity at test concentrations, the DCM extract was active only against Escherichia coli. However, the MeOH extract as well as the 50% and 80% SPE fractions of the MeOH extract showed significant antibacterial property against all bacterial strains tested. None of the extracts or fractions exhibited any significant toxicity towards brine shrimps.

  18. The Conformal Standard Model

    CERN Document Server

    Latosinski, Adam; Meissner, Krzysztof A; Nicolai, Hermann

    2015-01-01

    We present an extended version of the Conformal Standard Model (characterized by the absence of any new intermediate scales between the electroweak scale and the Planck scale) with an enlarged scalar sector coupling to right-chiral neutrinos in such a way that the scalar potential and the Yukawa couplings involving only right-chiral neutrinos are invariant under a new global symmetry SU(3)$_N$ which is broken explicitly only by the Yukawa interaction coupling right-chiral neutrinos and the electroweak lepton doublets. We point out four main advantages of such an enlargement, namely: (1) the economy of the (non-supersymmetric) Standard Model, and thus its observational success, is preserved; (2) thanks to the enlarged scalar sector the RG improved one-loop effective potential is everywhere positive with a stable global minimum, thereby avoiding the notorious instability of the Standard Model vacuum; (3) the pseudo-Goldstone bosons resulting from spontaneous breaking of the SU(3)$_N$ symmetry are natural Dark M...

  19. Conformational Dynamics of Insulin

    Directory of Open Access Journals (Sweden)

    Qing-xin eHua

    2011-10-01

    Full Text Available We have exploited a prandial insulin analogue (insulin lispro, the active component of Humalog®; Eli Lilly and Co. to elucidate the underlying structure and dynamics of insulin as a monomer in solution. Whereas NMR-based modeling recapitulates structural relationships of insulin crystals (T-state protomers, dynamic anomalies are revealed by amide-proton exchange kinetics in D2O. Surprisingly, the majority of hydrogen bonds observed in crystal structures are only transiently maintained in solution, including key T-state-specific inter-chain contacts. Long-lived hydrogen bonds (as defined by global exchange kinetics exist only at a subset of four -helical sites (two per chain flanking an internal disulfide bridge (cystine A20-B19; these sites map within the proposed folding nucleus of proinsulin. The anomalous flexibility of insulin otherwise spans its active surface and may facilitate receptor binding. Because conformational fluctuations promote the degradation of pharmaceutical formulations, we envisage that dynamic re-engineering of insulin may enable design of ultra-stable formulations for humanitarian use in the developing world.

  20. Using local states to drive the sampling of global conformations in proteins

    OpenAIRE

    Pandini, A; Fornili, A

    2016-01-01

    Conformational changes associated with protein function often occur beyond the time scale currently accessible to unbiased molecular dynamics (MD) simulations, so that different approaches have been developed to accelerate their sampling. Here we investigate how the knowledge of backbone conformations preferentially adopted by protein fragments, as contained in precalculated libraries known as structural alphabets (SA), can be used to explore the landscape of protein conformations in MD simul...

  1. Regular Submanifolds in Conformal Space Qnp

    Institute of Scientific and Technical Information of China (English)

    Changxiong NIE; Chuanxi WU

    2012-01-01

    The authors study the regular submanifolds in the conformal space Qnp and introduce the submanifold theory in the conformal space Qnp.The first variation formula of the Willmore volume functional of pseudo-Riemannian submanifolds in the conformal space Qnp is given.Finally,the conformal isotropic submanifolds in the conformal space Qnp are classified.

  2. On the geometry and conformation of starburst dendrimers

    CERN Document Server

    De Pádua, A B; Moraes, F; Padua, Antonio de; Moraes, Fernando

    1995-01-01

    In this work, we propose a geometrical model for the study of conformational properties of a starburst dendrimer with the topology of a truncated Bethe lattice. A convenient embedding of the Bethe lattice in the hyperbolic plane is used to study the architecture of the dendrimer. As results, we find an upper bound for the molecular size and the density profile.

  3. Photoregulation of polymer conformation. A modelstudy for biology

    NARCIS (Netherlands)

    Veen, Gerlof van der

    1972-01-01

    SUMMARY A conformational transition of a macromolecule is often postulated to occur in biological energy transductions. When +he energy of a photon is transduced, a photochromic ligand mediates in the transfer of energy from the sun to the macromolecule. In this thesis the molecular mechanism of tho

  4. Towards conformal loop quantum gravity

    Science.gov (United States)

    H-T Wang, Charles

    2006-03-01

    A discussion is given of recent developments in canonical gravity that assimilates the conformal analysis of gravitational degrees of freedom. The work is motivated by the problem of time in quantum gravity and is carried out at the metric and the triad levels. At the metric level, it is shown that by extending the Arnowitt-Deser-Misner (ADM) phase space of general relativity (GR), a conformal form of geometrodynamics can be constructed. In addition to the Hamiltonian and Diffeomorphism constraints, an extra first class constraint is introduced to generate conformal transformations. This phase space consists of York's mean extrinsic curvature time, conformal three-metric and their momenta. At the triad level, the phase space of GR is further enlarged by incorporating spin-gauge as well as conformal symmetries. This leads to a canonical formulation of GR using a new set of real spin connection variables. The resulting gravitational constraints are first class, consisting of the Hamiltonian constraint and the canonical generators for spin-gauge and conformorphism transformations. The formulation has a remarkable feature of being parameter-free. Indeed, it is shown that a conformal parameter of the Barbero-Immirzi type can be absorbed by the conformal symmetry of the extended phase space. This gives rise to an alternative approach to loop quantum gravity that addresses both the conceptual problem of time and the technical problem of functional calculus in quantum gravity.

  5. Towards conformal loop quantum gravity

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Charles H-T [School of Engineering and Physical Sciences, University of Aberdeen, King' s College, Aberdeen AB24 3UE (United Kingdom); Space Science and Technology Department, Rutherford Appleton Laboratory, Didcot, Oxon OX11 0QX (United Kingdom)

    2006-03-01

    A discussion is given of recent developments in canonical gravity that assimilates the conformal analysis of gravitational degrees of freedom. The work is motivated by the problem of time in quantum gravity and is carried out at the metric and the triad levels. At the metric level, it is shown that by extending the Arnowitt-Deser-Misner (ADM) phase space of general relativity (GR), a conformal form of geometrodynamics can be constructed. In addition to the Hamiltonian and Diffeomorphism constraints, an extra first class constraint is introduced to generate conformal transformations. This phase space consists of York's mean extrinsic curvature time, conformal three-metric and their momenta. At the triad level, the phase space of GR is further enlarged by incorporating spin-gauge as well as conformal symmetries. This leads to a canonical formulation of GR using a new set of real spin connection variables. The resulting gravitational constraints are first class, consisting of the Hamiltonian constraint and the canonical generators for spin-gauge and conformorphism transformations. The formulation has a remarkable feature of being parameter-free. Indeed, it is shown that a conformal parameter of the Barbero-Immirzi type can be absorbed by the conformal symmetry of the extended phase space. This gives rise to an alternative approach to loop quantum gravity that addresses both the conceptual problem of time and the technical problem of functional calculus in quantum gravity.

  6. Locally conformal symplectic manifolds

    Directory of Open Access Journals (Sweden)

    Izu Vaisman

    1985-01-01

    Full Text Available A locally conformal symplectic (l. c. s. manifold is a pair (M2n,Ω where M2n(n>1 is a connected differentiable manifold, and Ω a nondegenerate 2-form on M such that M=⋃αUα (Uα- open subsets. Ω/Uα=eσαΩα, σα:Uα→ℝ, dΩα=0. Equivalently, dΩ=ω∧Ω for some closed 1-form ω. L. c. s. manifolds can be seen as generalized phase spaces of Hamiltonian dynamical systems since the form of the Hamilton equations is, in fact, preserved by homothetic canonical transformations. The paper discusses first Hamiltonian vector fields, and infinitesimal automorphisms (i. a. on l. c. s. manifolds. If (M,Ω has an i. a. X such that ω(X≠0, we say that M is of the first kind and Ω assumes the particular form Ω=dθ−ω∧θ. Such an M is a 2-contact manifold with the structure forms (ω,θ, and it has a vertical 2-dimensional foliation V. If V is regular, we can give a fibration theorem which shows that M is a T2-principal bundle over a symplectic manifold. Particularly, V is regular for some homogeneous l. c. s, manifolds, and this leads to a general construction of compact homogeneous l. c. s, manifolds. Various related geometric results, including reductivity theorems for Lie algebras of i. a. are also given. Most of the proofs are adaptations of corresponding proofs in symplectic and contact geometry. The paper ends with an Appendix which states an analogous fibration theorem in Riemannian geometry.

  7. Conformal Tensors via Lovelock Gravity

    CERN Document Server

    Kastor, David

    2013-01-01

    Constructs from conformal geometry are important in low dimensional gravity models, while in higher dimensions the higher curvature interactions of Lovelock gravity are similarly prominent. Considering conformal invariance in the context of Lovelock gravity leads to natural, higher-curvature generalizations of the Weyl, Schouten, Cotton and Bach tensors, with properties that straightforwardly extend those of their familiar counterparts. As a first application, we introduce a new set of conformally invariant gravity theories in D=4k dimensions, based on the squares of the higher curvature Weyl tensors.

  8. Conformal Patterson-Walker metrics

    CERN Document Server

    Hammerl, Matthias; Šilhan, Josef; Taghavi-Chabert, Arman; Žádník, Vojtěch

    2016-01-01

    The classical Patterson-Walker construction of a split-signature (pseudo-)Riemannian structure from a given torsion-free affine connection is generalized to a construction of a split-signature conformal structure from a given projective class of connections. A characterization of the induced structures is obtained. We achieve a complete description of Einstein metrics in the conformal class formed by the Patterson-Walker metric. Finally, we describe all symmetries of the conformal Patterson-Walker metric. In both cases we obtain descriptions in terms of geometric data on the original structure.

  9. Conformally reducible 2+2 spacetimes

    Energy Technology Data Exchange (ETDEWEB)

    Carot, Jaume [Departament de Fisica, Universitat de les Illes Balears, Cra. Valldemossa km 7.5, E-07071 Palma de Mallorca (Spain); Tupper, Brian O J [Department of Mathematics and Statistics, University of New Brunswick, Fredericton, NB E3B 5A3 (Canada)

    2002-08-07

    Spacetimes which are conformal to 2+2 reducible spacetimes are considered. We classify them according to their conformal algebra, giving in each case explicit expressions for the metric and conformal Killing vectors, and providing physically meaningful examples.

  10. Conformally reducible 2+2 spacetimes

    CERN Document Server

    Carot, J

    2002-01-01

    Spacetimes which are conformal to 2+2 reducible spacetimes are considered. We classify them according to their conformal algebra, giving in each case explicit expressions for the metric and conformal Killing vectors, and providing physically meaningful examples.

  11. Pressurization of bioactive bone cement in vitro.

    Science.gov (United States)

    Fujita, H; Iida, H; Kawanabe, K; Okada, Y; Oka, M; Masuda, T; Kitamura, Y; Nakamura, T

    1999-01-01

    We have developed a bioactive bone cement consisting of MgO-CaO-SiO2-P2O5-CaF2 glass-ceramic powder (AW glass-ceramic powder), silica glass powder as an inorganic filler, and bisphenol-a-glycidyl methacrylate (bis-GMA) based resin as an organic matrix. The efficacy of this bioactive bone cement was investigated by evaluating its pressurization in a 5-mm hole and small pores using a simulated acetabular cavity. Two types of acetabular components were used (flanged and unflanged sockets) and a commercially available polymethylmethacrylate (PMMA) bone cement (CMW 1 Radiopaque Bone Cement) was selected as a comparative control. Bioactive bone cement exerted greater intrusion volume in 5-mm holes than PMMA bone cement in both the flanged and unflanged sockets 10 minutes after pressurization (p anchor holes than PMMA bone cement.

  12. Ligand-induced conformational changes: Improved predictions of ligand binding conformations and affinities

    DEFF Research Database (Denmark)

    Frimurer, T.M.; Peters, Günther H.J.; Iversen, L.F.;

    2003-01-01

    A computational docking strategy using multiple conformations of the target protein is discussed and evaluated. A series of low molecular weight, competitive, nonpeptide protein tyrosine phosphatase inhibitors are considered for which the x-ray crystallographic structures in complex with protein...... tyrosine phosphatase 1 B (PTP1B) are known. To obtain a quantitative measure of the impact of conformational changes induced by the inhibitors, these were docked to the active site region of various structures of PTP1B using the docking program FlexX. Firstly, the inhibitors were docked to a PTP1B crystal...... with low estimated binding energies corresponded to relatively large RMS differences when aligned with the corresponding crystal structure. Secondly, the inhibitors were docked to their parent protein structures in which they were cocrystallized. In this case, there was a good correlation between low...

  13. Different molecular conformations co-exist in each of three 2-aryl-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamides: hydrogen bonding in zero, one and two dimensions.

    Science.gov (United States)

    Narayana, Badiadka; Yathirajan, Hemmige S; Rathore, Ravindranath S; Glidewell, Christopher

    2016-09-01

    4-Antipyrine [4-amino-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one] and its derivatives exhibit a range of biological activities, including analgesic, antibacterial and anti-inflammatory, and new examples are always of potential interest and value. 2-(4-Chlorophenyl)-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamide, C19H18ClN3O2, (I), crystallizes with Z' = 2 in the space group P\\overline{1}, whereas its positional isomer 2-(2-chlorophenyl)-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)acetamide, (II), crystallizes with Z' = 1 in the space group C2/c; the molecules of (II) are disordered over two sets of atomic sites having occupancies of 0.6020 (18) and 0.3980 (18). The two independent molecules of (I) adopt different molecular conformations, as do the two disorder components in (II), where the 2-chlorophenyl substituents adopt different orientations. The molecules of (I) are linked by a combination of N-H...O and C-H...O hydrogen bonds to form centrosymmetric four-molecule aggregates, while those of (II) are linked by the same types of hydrogen bonds forming sheets. The related compound N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-2-(3-methoxyphenyl)acetamide, C20H21N3O3, (III), is isomorphous with (I) but not strictly isostructural; again the two independent molecules adopt different molecular conformations, and the molecules are linked by N-H...O and C-H...O hydrogen bonds to form ribbons. Comparisons are made with some related structures, indicating that a hydrogen-bonded R2(2)(10) ring is the common structural motif. PMID:27585929

  14. Conformational study of neutral histamine monomer and their vibrational spectra.

    Science.gov (United States)

    Mukherjee, V; Yadav, T

    2016-08-01

    Molecular modeling and potential energy scanning of histamine molecule, which is an important neurotransmitter, with respect to the dihedral angle of methylamine side chain have done which prefer three different conformers of histamine monomer. We have calculated molecular structures and vibrational spectra with IR and Raman intensities of these conformers using Density Functional Theory (DFT) with the exchange functional B3LYP incorporated with the basis set 6-31++G(d,p) and Hartree-Fock (HF) with the same basis set. We have also employed normal coordinate analysis (NCA) to scale the theoretical frequencies and to calculate potential energy distributions (PEDs) for the conspicuous assignments. Normal modes assignments of some of the vibrational frequencies of all the three conformers are in good agreement with the earlier reported experimental frequencies of histamine whereas others have modified. The standard deviations between the theoretical and experimental frequencies fall in the region 13-20cm(-1) for the three conformers. NBO analyses of histamine conformers were also performed. The net charge transfers from ethylamine side chain to the imidazole ring. The intensive interactions between bonding and anti-bonding orbitals are found in imidazole ring. The HOMO-LUMO energy gap is nearly 5.50eV. PMID:27155558

  15. Conformational study of neutral histamine monomer and their vibrational spectra

    Science.gov (United States)

    Mukherjee, V.; Yadav, T.

    2016-08-01

    Molecular modeling and potential energy scanning of histamine molecule, which is an important neurotransmitter, with respect to the dihedral angle of methylamine side chain have done which prefer three different conformers of histamine monomer. We have calculated molecular structures and vibrational spectra with IR and Raman intensities of these conformers using Density Functional Theory (DFT) with the exchange functional B3LYP incorporated with the basis set 6-31 ++G(d,p) and Hartree-Fock (HF) with the same basis set. We have also employed normal coordinate analysis (NCA) to scale the theoretical frequencies and to calculate potential energy distributions (PEDs) for the conspicuous assignments. Normal modes assignments of some of the vibrational frequencies of all the three conformers are in good agreement with the earlier reported experimental frequencies of histamine whereas others have modified. The standard deviations between the theoretical and experimental frequencies fall in the region 13-20 cm- 1 for the three conformers. NBO analyses of histamine conformers were also performed. The net charge transfers from ethylamine side chain to the imidazole ring. The intensive interactions between bonding and anti-bonding orbitals are found in imidazole ring. The HOMO-LUMO energy gap is nearly 5.50 eV.

  16. Logarithmic conformal field theory

    Science.gov (United States)

    Gainutdinov, Azat; Ridout, David; Runkel, Ingo

    2013-12-01

    Conformal field theory (CFT) has proven to be one of the richest and deepest subjects of modern theoretical and mathematical physics research, especially as regards statistical mechanics and string theory. It has also stimulated an enormous amount of activity in mathematics, shaping and building bridges between seemingly disparate fields through the study of vertex operator algebras, a (partial) axiomatisation of a chiral CFT. One can add to this that the successes of CFT, particularly when applied to statistical lattice models, have also served as an inspiration for mathematicians to develop entirely new fields: the Schramm-Loewner evolution and Smirnov's discrete complex analysis being notable examples. When the energy operator fails to be diagonalisable on the quantum state space, the CFT is said to be logarithmic. Consequently, a logarithmic CFT is one whose quantum space of states is constructed from a collection of representations which includes reducible but indecomposable ones. This qualifier arises because of the consequence that certain correlation functions will possess logarithmic singularities, something that contrasts with the familiar case of power law singularities. While such logarithmic singularities and reducible representations were noted by Rozansky and Saleur in their study of the U (1|1) Wess-Zumino-Witten model in 1992, the link between the non-diagonalisability of the energy operator and logarithmic singularities in correlators is usually ascribed to Gurarie's 1993 article (his paper also contains the first usage of the term 'logarithmic conformal field theory'). The class of CFTs that were under control at this time was quite small. In particular, an enormous amount of work from the statistical mechanics and string theory communities had produced a fairly detailed understanding of the (so-called) rational CFTs. However, physicists from both camps were well aware that applications from many diverse fields required significantly more

  17. Conformation of antifreeze glycoproteins as determined from conformational energy calculations and fully assigned proton NMR spectra

    Energy Technology Data Exchange (ETDEWEB)

    Bush, C.A.; Rao, B.N.N.

    1986-05-01

    The /sup 1/H NMR spectra of AFGP's ranging in molecular weight from 2600 to 30,000 Daltons isolated from several different species of polar fish have been measured. The spectrum of AFGP 1-4 from Pagothenia borchgrevinki with an average of 30 repeating subunits has a single resonance for each proton of the glycotripeptide repeating unit, (ala-(gal-(..beta..-1..-->..3) galNAc-(..cap alpha..--O-)thr-ala)/sub n/. Its /sup 1/H NMR spectrum including resonances of the amide protons has been completely assigned. Coupling constants and nuclear Overhauser enhancements (n.O.e.) between protons on distant residues imply conformational order. The 2600 dalton molecular weight glycopeptides (AFGP-8) have pro in place of ala at certain specific points in the sequence and AFGP-8R of Eleginus gracilis has arg in place of one thr. The resonances of pro and arg were assigned by decoupling. The resonances of the carboxy and amino terminals have distinct chemical shifts and were assigned in AFGP-8 of Boreogadus saida by titration. n.O.e. between ..cap alpha..--protons and amide protons of the adjacent residue (sequential n.O.e.) were used in assignments of additional resonances and to assign the distinctive resonances of thr followed by pro. Conformational energy calculations on the repeating glycotripeptide subunit of AFGP show that the ..cap alpha..--glucosidic linkage has a fixed conformation while the ..beta..--linkage is less rigid. A conformational model for AFGP 1-4, which is based on the calculations has the peptide in an extended left-handed helix with three residues per turn similar to polyproline II. The model is consistent with CD data, amide proton coupling constants, temperature dependence of amide proton chemical shifts.

  18. National Automated Conformity Inspection Process

    Data.gov (United States)

    Department of Transportation — The National Automated Conformity Inspection Process (NACIP) Application is intended to expedite the workflow process as it pertains to the FAA Form 81 0-10 Request...

  19. Some Progress in Conformal Geometry

    Directory of Open Access Journals (Sweden)

    Sun-Yung A. Chang

    2007-12-01

    Full Text Available This is a survey paper of our current research on the theory of partial differential equations in conformal geometry. Our intention is to describe some of our current works in a rather brief and expository fashion. We are not giving a comprehensive survey on the subject and references cited here are not intended to be complete. We introduce a bubble tree structure to study the degeneration of a class of Yamabe metrics on Bach flat manifolds satisfying some global conformal bounds on compact manifolds of dimension 4. As applications, we establish a gap theorem, a finiteness theorem for diffeomorphism type for this class, and diameter bound of the $sigma_2$-metrics in a class of conformal 4-manifolds. For conformally compact Einstein metrics we introduce an eigenfunction compactification. As a consequence we obtain some topological constraints in terms of renormalized volumes.

  20. Hierarchically Nanoporous Bioactive Glasses for High Efficiency Immobilization of Enzymes

    DEFF Research Database (Denmark)

    He, W.; Min, D.D.; Zhang, X.D.;

    2014-01-01

    Bioactive glasses with hierarchical nanoporosity and structures have been heavily involved in immobilization of enzymes. Because of meticulous design and ingenious hierarchical nanostructuration of porosities from yeast cell biotemplates, hierarchically nanostructured porous bioactive glasses can...

  1. Synthesis and evaluation of novel bioactive composite starch/bioactive glass microparticles

    OpenAIRE

    Silva, G. A.; Costa, F. J.; Coutinho, O. P.; Radin, S.; Ducheyne, P.; Reis, R. L.

    2004-01-01

    The aim of the development of composite materials is to combine the most desired properties of two or more materials. In this work, the biodegradable character, good controlled-release properties, and natural origin of starch-based biomaterials are combined with the bioactive and bone-bonding properties of bioactive glass (BG). Novel, bioactive composite starch-BG microparticles were synthesized starting from a blend of starch and polylactic acid (50%/50% wt) with BG 45S5 powder using a simpl...

  2. Selection of conformational states in self-assembled surface structures formed from an oligo(naphthylene-ethynylene) 3-bit binary switch

    DEFF Research Database (Denmark)

    Ning, Yanxiao; Cramer, Jacob Roland; Nuermaimaiti, Ajiguli;

    2015-01-01

    Supra-molecular self-assembly on surfaces often involves molecular conformational flexibility which may act to enrich the variation and complexity of the structures formed. However, systematic and explicit investigations of how molecular conformational states are selected in surface self-assembly...

  3. Methods of Manufacturing Bioactive Gels from Extracellular Matrix Material

    Science.gov (United States)

    Kentner, Kimberly A. (Inventor); Stuart, Katherine A. (Inventor); Janis, Abram D. (Inventor)

    2016-01-01

    The present invention is directed to methods of manufacturing bioactive gels from ECM material, i.e., gels which retain bioactivity, and can serve as scaffolds for preclinical and clinical tissue engineering and regenerative medicine approaches to tissue reconstruction. The manufacturing methods take advantage of a new recognition that bioactive gels from ECM material can be created by digesting particularized ECM material in an alkaline environment and neutralizing to provide bioactive gels.

  4. Mushroom Lectins: Specificity, Structure and Bioactivity Relevant to Human Disease

    Directory of Open Access Journals (Sweden)

    Mohamed Ali Abol Hassan

    2015-04-01

    Full Text Available Lectins are non-immunoglobulin proteins that bind diverse sugar structures with a high degree of selectivity. Lectins play crucial role in various biological processes such as cellular signaling, scavenging of glycoproteins from the circulatory system, cell–cell interactions in the immune system, differentiation and protein targeting to cellular compartments, as well as in host defence mechanisms, inflammation, and cancer. Among all the sources of lectins, plants have been most extensively studied. However, more recently fungal lectins have attracted considerable attention due to their antitumor, antiproliferative and immunomodulatory activities. Given that only 10% of mushroom species are known and have been taxonomically classified, mushrooms represent an enormous unexplored source of potentially useful and novel lectins. In this review we provide an up-to-date summary on the biochemical, molecular and structural properties of mushroom lectins, as well as their versatile applications specifically focusing on mushroom lectin bioactivity.

  5. Computer graphic modeling in drug design--conformational analysis of antifolate binding to avian dihydrofolate reductase: crystal and molecular structures of 2,4-diamino-5-cyclohexyl-6-methylpyrimidine and 5-cyclohexyl-6-methyluracil.

    Science.gov (United States)

    Cody, V; Ciszak, E

    1991-05-01

    The results of crystal structure determinations of the antifolate 2,4-diamino-5-cyclohexyl-6-methylprimidine (I), and its uracil derivative (II), show that the 5-cyclohexyl ring is gauche to the planar pyrimidine ring with torsion angles 82.4 (3) degrees and 63.7 (3) degrees for (I) and (II), respectively. Hydrogen bond patterns observed for these free base pyrimidines indicate a preference for N...N or N...O dimer formation around inversion centers, as observed in other antifolate structures. Computer graphic modeling studies were carried out comparing the avian dihydrofolate reductase active site interactions of the cyclohexyl antifolate (I) with the more potent 5-adamantyl analog and the less potent 5-hexyl and 5-heptyl antifolates. These data showed that although the cyclohexyl ring fits into the same conformational space as adamantyl, it makes fewer hydrophobic contacts. Similarly, cyclohexyl fills the active site better than either the 5-n-hexyl or heptyl side chains. These data are consistent with the increased potency of the adamantyl and cyclohexyl antifolates compared to n-alkyl analogs with similar hydrophobicities. These data indicate that the rigid structure of these ring systems increases their hydrophobic interactions, thus enhancing their biochemical activity.

  6. Delineating the conformational flexibility of trisaccharides from NMR spectroscopy experiments and computer simulations.

    Science.gov (United States)

    Yang, Mingjun; Angles d'Ortoli, Thibault; Säwén, Elin; Jana, Madhurima; Widmalm, Göran; MacKerell, Alexander D

    2016-07-28

    The conformation of saccharides in solution is challenging to characterize in the context of a single well-defined three-dimensional structure. Instead, they are better represented by an ensemble of conformations associated with their structural diversity and flexibility. In this study, we delineate the conformational heterogeneity of five trisaccharides via a combination of experimental and computational techniques. Experimental NMR measurements target conformationally sensitive parameters, including J couplings and effective distances around the glycosidic linkages, while the computational simulations apply the well-calibrated additive CHARMM carbohydrate force field in combination with efficient enhanced sampling molecular dynamics simulation methods. Analysis of conformational heterogeneity is performed based on sampling of discreet states as defined by dihedral angles, on root-mean-square differences of Cartesian coordinates and on the extent of volume sampled. Conformational clustering, based on the glycosidic linkage dihedral angles, shows that accounting for the full range of sampled conformations is required to reproduce the experimental data, emphasizing the utility of the molecular simulations in obtaining an atomic detailed description of the conformational properties of the saccharides. Results show the presence of differential conformational preferences as a function of primary sequence and glycosidic linkage types. Significant differences in conformational ensembles associated with the anomeric configuration of a single glycosidic linkage reinforce the impact of such changes on the conformational properties of carbohydrates. The present structural insights of the studied trisaccharides represent a foundation for understanding the range of conformations adopted in larger oligosaccharides and how these molecules encode their conformational heterogeneity into the monosaccharide sequence. PMID:27346493

  7. Computerized molecular modeling of carbohydrates

    Science.gov (United States)

    Computerized molecular modleing continues to increase in capability and applicability to carbohydrates. This chapter covers nomenclature and conformational aspects of carbohydrates, perhaps of greater use to carbohydrate-inexperienced computational chemists. Its comments on various methods and studi...

  8. Encapsulation for preservation of functionality and targeted delivery of bioactive food components

    NARCIS (Netherlands)

    de Vos, Paul; Faas, Marijke M.; Spasojevic, Milica; Sikkema, Jan

    2010-01-01

    There has been a tremendous increase in the number of food products containing bioactive components with a health promoting or disease preventing effect. Bioactive food components can be divided into bioactive molecules and bioactive living cells (probiotics). Both bioactive molecules and bioactive

  9. Lipids and Fatty Acids of Nudibranch Mollusks: Potential Sources of Bioactive Compounds

    OpenAIRE

    Zhukova, Natalia V

    2014-01-01

    The molecular diversity of chemical compounds found in marine animals offers a good chance for the discovery of novel bioactive compounds of unique structures and diverse biological activities. Nudibranch mollusks, which are not protected by a shell and produce chemicals for various ecological uses, including defense against predators, have attracted great interest for their lipid composition. Lipid analysis of eight nudibranch species revealed dominant phospholipids, sterols and monoalkyldia...

  10. Study on the bioactivity changes of hydroxylated sulfonylureas derivatives: A possible metabolism

    Institute of Scientific and Technical Information of China (English)

    Shu Rong Ban; Cong Wei Niu; Wen Bin Chen; Zhi Hong Yu; Si Wu; Chen Wang; Zhen Xi

    2007-01-01

    Some new sulfonylureas and their hydroxylation products had been synthesized from 2-amino-4-methylpyrimidine. Their bioactivities against E. Coli AHAS Ⅱ in vitro were tested and the results indicated that the hydroxylation decreased the inhibition activities of sulfonylureas significantly. Subsequently herbicidal tests against stem-growth of barnyard grass and root-growth of rape confirmed the above conclusion. The preliminary molecular docking studies were also carried out to investigate the binding modes of non-hydroxylated and hydroxylated sulfonylureas with AHAS.

  11. Determination of The Bioactive Compund and Total Antioxidant Capacity of Apple Species Grown Around Ardahan Region

    OpenAIRE

    Z. A. ABACI; E. SEVİNDİK; Coşkun, F.; K. GEZER; A. CELİK; O. KAYGUSUZ; A. ERMİŞ

    2014-01-01

    Phenolic compounds are seconder metabolytes that have low molecular weight amd they have a high density of presence in frruits and vegetables. Also, they have a antioxidative capacity compared to other bioactive compounds. It was suggested by several researchers that they have beneficial effects that improve human health. It was asserted that Phenolic compounds inhibit cancer cells, helps to decrease blood pressure and antimutagenic activity and it also aids in lowering cardiovascular risks. ...

  12. Conformational fluctuations affect protein alignment in dilute liquid crystal media

    DEFF Research Database (Denmark)

    Louhivuori, M.; Otten, R.; Lindorff-Larsen, Kresten;

    2006-01-01

    The discovery of dilute liquid crystalline media to align biological macromolecules has opened many new possibilities to study protein and nucleic acid structures by NMR spectroscopy. We inspect the basic alignment phenomenon for an ensemble of protein conformations to deduce relative contributions...... of each member to the residual dipolar coupling signals. We find that molecular fluctuations can affect the alignment and discover a resulting emphasis of certain conformations. However, the internal fluctuations are largely uncorrelated with those of the alignment, implying that proteins have liquidlike...

  13. Fluctuation Flooding Method (FFM) for accelerating conformational transitions of proteins

    Science.gov (United States)

    Harada, Ryuhei; Takano, Yu; Shigeta, Yasuteru

    2014-03-01

    A powerful conformational sampling method for accelerating structural transitions of proteins, "Fluctuation Flooding Method (FFM)," is proposed. In FFM, cycles of the following steps enhance the transitions: (i) extractions of largely fluctuating snapshots along anisotropic modes obtained from trajectories of multiple independent molecular dynamics (MD) simulations and (ii) conformational re-sampling of the snapshots via re-generations of initial velocities when re-starting MD simulations. In an application to bacteriophage T4 lysozyme, FFM successfully accelerated the open-closed transition with the 6 ns simulation starting solely from the open state, although the 1-μs canonical MD simulation failed to sample such a rare event.

  14. Preparation of bioactive glasses with controllable degradation behavior and their bioactive characterization

    Institute of Scientific and Technical Information of China (English)

    YAO AiHua; WANG DePing; FU Qiang; HUANG WenHai; Mohamed N. RAHAMAN

    2007-01-01

    Bioactive glasses and ceramics have been widely investigated for bone repair because of their excellent bioactive characteristics. However, these biomaterials undergo incomplete conversion into a bone-like material, which severely limits their biomedical application. In this paper, borosilicate bioactive glasses were prepared by traditional melting process. The results showed that borosilicate glasses possessed high biocompatibility and bioactivity. In addition, when immersed in a 0.02 mol/L K2HPO4 solution, particles of a borate glass were fully converted to HA. The desirable conversion rate to HA may be achieved through the adjustment of the B2O3/SiO2 ratio. The results of XRD and FTIR analysis indicated that the degradation product was carbonate-substituted hydroxyapatite, which was similar to the inorganic component of bone.

  15. Bioactive Terpenes from Marine-Derived Fungi

    Directory of Open Access Journals (Sweden)

    Ahmed M. Elissawy

    2015-04-01

    Full Text Available Marine-derived fungi continue to be a prolific source of secondary metabolites showing diverse bioactivities. Terpenoids from marine-derived fungi exhibit wide structural diversity including numerous compounds with pronounced biological activities. In this review, we survey the last five years’ reports on terpenoidal metabolites from marine-derived fungi with particular attention on those showing marked biological activities.

  16. Glutathione conjugation as a bioactivation reaction

    NARCIS (Netherlands)

    Bladeren, P.J. van

    2000-01-01

    In general, glutathione conjugation is regarded as a detoxication reaction. However, depending on the properties of the substrate, bioactivation is also possible. Four types of activation reaction have been recognized: direct-acting compounds, conjugates that are activated through cysteine conjugate

  17. Marine Bioactives and Potential Application in Sports

    Directory of Open Access Journals (Sweden)

    Maria Alessandra Gammone

    2014-04-01

    Full Text Available An enriched diet with antioxidants, such as vitamin E, vitamin C, β-carotene and phenolic compounds, has always been suggested to improve oxidative stress, preventing related diseases. In this respect, marine natural product (MNP, such as COX inhibitors, marine steroids, molecules interfering with factors involved in the modulation of gene expression (such as NF-κB, macrolides, many antioxidant agents, thermogenic substances and even substances that could help the immune system and that result in the protection of cartilage, have been recently gaining attention. The marine world represents a reserve of bioactive ingredients, with considerable potential as functional food. Substances, such as chitin, chitosan, n-3 oils, carotenoids, vitamins, minerals and bioactive peptides, can provide several health benefits, such as the reduction of cardiovascular diseases, anti-inflammatory and anticarcinogenic activities. In addition, new marine bioactive substances with potential anti-inflammatory, antioxidant and thermogenic capacity may provide health benefits and performance improvement, especially in those who practice physical activity, because of their increased free radical and Reacting Oxygen Species (ROS production during exercise, and, particularly, in athletes. The aim of this review is to examine the potential pharmacological properties and application of many marine bioactive substances in sports.

  18. Bioactive alkaloids in vertically transmitted fungal endophytes

    Science.gov (United States)

    Plants form mutualistic symbioses with a variety of microorganisms, including endophytic fungi that live inside the plant and cause no symptoms of infection. Some endophytic fungi form defensive mutualisms based on the production of bioactive metabolites that protect the plant from herbivores in exc...

  19. Citrus Limonoids: Analysis, Bioactivity, and Biomedical Prospects

    Science.gov (United States)

    This publication is a review of the chemistry, biochemistry and bioactivity of limonoids occurring in citrus. The review chronologically relates the evolution of research in citrus limonoids beginning with their association with bitterness development in citrus juices. The chemical and biochemical...

  20. Marine bioactives and potential application in sports.

    Science.gov (United States)

    Gammone, Maria Alessandra; Gemello, Eugenio; Riccioni, Graziano; D'Orazio, Nicolantonio

    2014-04-30

    An enriched diet with antioxidants, such as vitamin E, vitamin C, β-carotene and phenolic compounds, has always been suggested to improve oxidative stress, preventing related diseases. In this respect, marine natural product (MNP), such as COX inhibitors, marine steroids, molecules interfering with factors involved in the modulation of gene expression (such as NF-κB), macrolides, many antioxidant agents, thermogenic substances and even substances that could help the immune system and that result in the protection of cartilage, have been recently gaining attention. The marine world represents a reserve of bioactive ingredients, with considerable potential as functional food. Substances, such as chitin, chitosan, n-3 oils, carotenoids, vitamins, minerals and bioactive peptides, can provide several health benefits, such as the reduction of cardiovascular diseases, anti-inflammatory and anticarcinogenic activities. In addition, new marine bioactive substances with potential anti-inflammatory, antioxidant and thermogenic capacity may provide health benefits and performance improvement, especially in those who practice physical activity, because of their increased free radical and Reacting Oxygen Species (ROS) production during exercise, and, particularly, in athletes. The aim of this review is to examine the potential pharmacological properties and application of many marine bioactive substances in sports.

  1. Bioactive compounds in whole grain wheat

    NARCIS (Netherlands)

    Mateo Anson, N.

    2010-01-01

    Bread can be healthier! Consuming whole-grain foods can prevent cardiovascular diseases, type-2 diabetes and metabolic syndrome. This is due to bioactive compounds in whole grain, such as antioxidants and anti-inflammatory compounds. We found that the different fractions of a wheat grain vary much i

  2. Preparation and bioactive properties of nano bioactive glass and segmented polyurethane composites.

    Science.gov (United States)

    Aguilar-Pérez, Fernando J; Vargas-Coronado, Rossana F; Cervantes-Uc, Jose M; Cauich-Rodríguez, Juan V; Covarrubias, Cristian; Pedram-Yazdani, Merhdad

    2016-04-01

    Composites of glutamine-based segmented polyurethanes with 5 to 25 wt.% bioactive glass nanoparticles were prepared, characterized, and their mineralization potential was evaluated in simulated body fluid. Biocompatibility with dental pulp stem cells was assessed by MTS to an extended range of compositions (1 to 25 wt.% of bioactive glass nanoparticles). Physicochemical characterization showed that composites retained many of the matrix properties, i.e. those corresponding to semicrystalline elastomeric polymers as they exhibited a glass transition temperature (Tg) between -41 and -36℃ and a melting temperature (Tm) between 46 and 49℃ in agreement with X-ray reflections at 23.6° and 21.3°. However, with bioactive glass nanoparticles addition, tensile strength and strain were reduced from 22.2 to 12.2 MPa and 667.2 to 457.8%, respectively with 25 wt.% of bioactive glass nanoparticles. Although Fourier transform infrared spectroscopy did not show evidence of mineralization after conditioning of these composites in simulated body fluid, X-ray diffraction, scanning electron microscopy, and energy dispersive X-ray microanalysis showed the formation of an apatite layer on the surface which increased with higher bioactive glass concentrations and longer conditioning time. Dental pulp stem cells proliferation at day 5 was improved in bioactive glass nanoparticles composites containing lower amounts of the filler (1-2.5 wt.%) but it was compromised at day 9 in composites containing high contents of nBG (5, 15, 25 wt.%). However, Runx2 gene expression was particularly upregulated for the dental pulp stem cells cultured with composites loaded with 15 and 25 wt.% of bioactive glass nanoparticles. In conclusion, low content bioactive glass nanoparticles and segmented polyurethanes composites deserve further investigation for applications such as guided bone regeneration membranes, where osteoconductivity is desirable but not a demanding mechanical performance.

  3. Conformal Window and Correlation Functions in Lattice Conformal QCD

    CERN Document Server

    Iwasaki, Y

    2012-01-01

    We discuss various aspects of Conformal Field Theories on the Lattice. We investigate the SU(3) gauge theory with Nf fermions in the fundamental representation. First we make a brief review of our previous works on the phase structure of lattice gauge theories in terms of the gauge coupling constant and the quark mass. We thereby clarify the reason why we conjecture that the conformal window is 7 = 1 exhibit the characteristics of the conformal function with IR cutoff, an exponential damping with power correction. Investigating our numerical data by a new method, the "micro-analysis" of propagators, we observe that our data are consistent with the picture that the Nf=7 case and the Nf=2 at T ~ 2Tc case are close to the meson unparticle model. On the other hand, the Nf=16 case and the Nf=2 at T= 10^2 ~10^5 Tc cases are close to the fermion unparticle model.

  4. Bioactive macroporous titanium implants highly interconnected.

    Science.gov (United States)

    Caparrós, Cristina; Ortiz-Hernandez, Mónica; Molmeneu, Meritxell; Punset, Miguel; Calero, José Antonio; Aparicio, Conrado; Fernández-Fairén, Mariano; Perez, Román; Gil, Francisco Javier

    2016-10-01

    Intervertebral implants should be designed with low load requirements, high friction coefficient and low elastic modulus in order to avoid the stress shielding effect on bone. Furthermore, the presence of a highly interconnected porous structure allows stimulating bone in-growth and enhancing implant-bone fixation. The aim of this study was to obtain bioactive porous titanium implants with highly interconnected pores with a total porosity of approximately 57 %. Porous Titanium implants were produced by powder sintering route using the space holder technique with a binder phase and were then evaluated in an in vivo study. The size of the interconnection diameter between the macropores was about 210 μm in order to guarantee bone in-growth through osteblastic cell penetration. Surface roughness and mechanical properties were analyzed. Stiffness was reduced as a result of the powder sintering technique which allowed the formation of a porous network. Compression and fatigue tests exhibited suitable properties in order to guarantee a proper compromise between mechanical properties and pore interconnectivity. Bioactivity treatment effect in novel sintered porous titanium materials was studied by thermo-chemical treatments and were compared with the same material that had undergone different bioactive treatments. Bioactive thermo-chemical treatment was confirmed by the presence of sodium titanates on the surface of the implants as well as inside the porous network. Raman spectroscopy results suggested that the identified titanate structures would enhance in vivo apatite formation by promoting ion exchange for the apatite formation process. In vivo results demonstrated that the bioactive titanium achieved over 75 % tissue colonization compared to the 40 % value for the untreated titanium. PMID:27582071

  5. Trace Levels of Staphylococcal Enterotoxin Bioactivity Are Concealed in a Mucosal Niche during Pulmonary Inflammation.

    Directory of Open Access Journals (Sweden)

    Antoine Ménoret

    Full Text Available Pathogen and cellular by-products released during infection or trauma are critical for initiating mucosal inflammation. The localization of these factors, their bioactivity and natural countermeasures remain unclear. This concept was studied in mice undergoing pulmonary inflammation after Staphylococcal enterotoxin A (SEA inhalation. Highly purified bronchoalveolar lavage fluid (BALF fractions obtained by sequential chromatography were screened for bioactivity and subjected to mass spectrometry. The Inflammatory and inhibitory potentials of the identified proteins were measured using T cells assays. A potent pro-inflammatory factor was detected in BALF, and we hypothesized SEA could be recovered with its biological activity. Highly purified BALF fractions with bioactivity were subjected to mass spectrometry. SEA was the only identified protein with known inflammatory potential, and unexpectedly, it co-purified with immunosuppressive proteins. Among them was lactoferrin, which inhibited SEA and anti-CD3/-CD28 stimulation by promoting T cell death and reducing TNF synthesis. Higher doses of lactoferrin were required to inhibit effector compared to resting T cells. Inhibition relied on the continual presence of lactoferrin rather than a programming event. The data show a fraction of bioactive SEA resided in a mucosal niche within BALF even after the initiation of inflammation. These results may have clinical value in human diagnostic since traces levels of SEA can be detected using a sensitive bioassay, and may help pinpoint potential mediators of lung inflammation when molecular approaches fail.

  6. 40 CFR 93.154 - Conformity analysis.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Conformity analysis. 93.154 Section 93...) DETERMINING CONFORMITY OF FEDERAL ACTIONS TO STATE OR FEDERAL IMPLEMENTATION PLANS Determining Conformity of General Federal Actions to State or Federal Implementation Plans § 93.154 Conformity analysis. Any...

  7. Conformal Gravity Rotation Curves with a Conformal Higgs Halo

    CERN Document Server

    Horne, Keith

    2016-01-01

    We discuss the effect of a conformally coupled Higgs field on conformal gravity (CG) predictions for the rotation curves of galaxies. The Mannheim-Kazanas (MK) metric is a valid vacuum solution of CG's 4-th order Poisson equation only if the Higgs field has a particular radial profile, S(r)=S_0 a/(r+a), decreasing from S_0 at r=0 with radial scale length a. Since particle rest masses scale with S(r)/S_0, their world lines do not follow time-like geodesics of the MK metric g_{\\mu\

  8. Specific chemical reactivities of spatially separated 3-aminophenol conformers with cold Ca$^+$ ions

    CERN Document Server

    Chang, Yuan-Pin; Küpper, Jochen; Rösch, Daniel; Wild, Dieter; Willitsch, Stefan

    2013-01-01

    Many molecules exhibit multiple rotational isomers (conformers) that interconvert thermally and are difficult to isolate. Consequently, a precise characterization of their role in chemical reactions has proven challenging. We have probed the reactivity of specific conformers using an experimental technique based on their spatial separation in a molecular beam by electrostatic deflection. The separated conformers react with a target of Coulomb-crystallized ions in a trap. In the reaction of Ca$^+$ with 3-aminophenol, we find a twofold larger rate constant for the \\textit{cis}- compared to the \\textit{trans}-conformer (differentiated by the O-H bond orientation). This result is explained by conformer-specific differences in the long-range ion-molecule interaction potentials. Our approach demonstrates the possibility of controlling reactivity through selection of conformational states.

  9. New potentials for conformal mechanics

    CERN Document Server

    Papadopoulos, G

    2012-01-01

    We show that V=\\alpha x^2+\\beta x^{-2} arises as a potential of 1-dimensional conformal theories. This class of conformal models includes the DFF model \\alpha=0 and the harmonic oscillator \\beta=0. The construction is based on a different embedding of the conformal symmetry group into the time re-parameterizations from that of the DFF model and its generalizations. Depending on the range of the couplings $\\alpha, \\beta$, these models can have a ground state and a well-defined energy spectrum, and exhibit either a $SL(2,\\bR)$ or a SO(3) conformal symmetry. The latter group can also be embedded in Diff(S^1). We also present several generalizations of these models which include the Calogero models with harmonic oscillator couplings and non-linear models with suitable metric and potential couplings. In addition, we give the conditions on the couplings for a class of gaugetheories to admit a SL(2,\\bR) or SO(3) conformal symmetry. We present examples of such systems with general gauge groups and global symmetries t...

  10. Renyi entropy and conformal defects

    Energy Technology Data Exchange (ETDEWEB)

    Bianchi, Lorenzo [Humboldt-Univ. Berlin (Germany). Inst. fuer Physik; Hamburg Univ. (Germany). II. Inst. fuer Theoretische Physik; Meineri, Marco [Scuola Normale Superiore, Pisa (Italy); Perimeter Institute for Theoretical Physics, Waterloo, ON (Canada); Istituto Nazionale di Fisica Nucleare, Pisa (Italy); Myers, Robert C. [Perimeter Institute for Theoretical Physics, Waterloo, ON (Canada); Smolkin, Michael [California Univ., Berkely, CA (United States). Center for Theoretical Physics and Department of Physics

    2016-04-18

    We propose a field theoretic framework for calculating the dependence of Renyi entropies on the shape of the entangling surface in a conformal field theory. Our approach rests on regarding the corresponding twist operator as a conformal defect and in particular, we define the displacement operator which implements small local deformations of the entangling surface. We identify a simple constraint between the coefficient defining the two-point function of the displacement operator and the conformal weight of the twist operator, which consolidates a number of distinct conjectures on the shape dependence of the Renyi entropy. As an example, using this approach, we examine a conjecture regarding the universal coefficient associated with a conical singularity in the entangling surface for CFTs in any number of spacetime dimensions. We also provide a general formula for the second order variation of the Renyi entropy arising from small deformations of a spherical entangling surface, extending Mezei's results for the entanglement entropy.

  11. Lectures on Conformal Field Theory

    CERN Document Server

    Qualls, Joshua D

    2015-01-01

    These lectures notes are based on courses given at National Taiwan University, National Chiao-Tung University, and National Tsing Hua University in the spring term of 2015. Although the course was offered primarily for graduate students, these lecture notes have been prepared for a more general audience. They are intended as an introduction to conformal field theories in various dimensions, with applications related to topics of particular interest: topics include the conformal bootstrap program, boundary conformal field theory, and applications related to the AdS/CFT correspondence. We assume the reader to be familiar with quantum mechanics at the graduate level and to have some basic knowledge of quantum field theory. Familiarity with string theory is not a prerequisite for this lectures, although it can only help.

  12. Conformal Anomalies and Gravitational Waves

    CERN Document Server

    Meissner, Krzysztof A

    2016-01-01

    We argue that the presence of conformal anomalies in gravitational theories can lead to observable modifications to Einstein's equations via the induced anomalous effective actions, whose non-localities can overwhelm the smallness of the Planck scale. The fact that no such effects have been seen in recent cosmological or gravitational wave observations therefore imposes strong restrictions on the field content of possible extensions of Einstein's theory: all viable theories should have vanishing conformal anomalies. We then show that, among presently known theories, a complete cancellation of conformal anomalies in $D=4$ for both the $C^2$ invariant and the Euler (Gauss-Bonnet) invariant $E_4$ can only be achieved for $N$-extended supergravities with $N\\geq 5$, as well as for M theory compactified to four dimensions.

  13. Conformal geometry and quasiregular mappings

    CERN Document Server

    Vuorinen, Matti

    1988-01-01

    This book is an introduction to the theory of spatial quasiregular mappings intended for the uninitiated reader. At the same time the book also addresses specialists in classical analysis and, in particular, geometric function theory. The text leads the reader to the frontier of current research and covers some most recent developments in the subject, previously scatterd through the literature. A major role in this monograph is played by certain conformal invariants which are solutions of extremal problems related to extremal lengths of curve families. These invariants are then applied to prove sharp distortion theorems for quasiregular mappings. One of these extremal problems of conformal geometry generalizes a classical two-dimensional problem of O. Teichmüller. The novel feature of the exposition is the way in which conformal invariants are applied and the sharp results obtained should be of considerable interest even in the two-dimensional particular case. This book combines the features of a textbook an...

  14. Conformal Mapping for Multiple Terminals

    CERN Document Server

    Wang, Weimin; Wang, Qiang; Ren, Hao

    2015-01-01

    Conformal mapping is an important mathematical tool in many physical and engineering fields, especially in electrostatics, fluid mechanics, classical mechanics, and transformation optics. However in the existing textbooks and literatures, it is only adopted to solve the problems which have only two terminals. Two terminals with electric potential differences, pressure difference, optical path difference, etc., can be mapped conformally onto a solvable structure, e.g., a rectangle, where the two terminals are mapped onto two opposite edges of the rectangle. Here we show a conformal mapping method for multiple terminals, which is more common in practical applications. Through accurate analysis of the boundary conditions, additional terminals or boundaries are folded in the inner of the mapped rectangle. Then the solution will not be influenced. The method is described in several typical situations and two application examples are detailed. The first example is an electrostatic actuator with three electrodes. A ...

  15. Universality class in conformal inflation

    Energy Technology Data Exchange (ETDEWEB)

    Kallosh, Renata; Linde, Andrei, E-mail: kallosh@stanford.edu, E-mail: alinde@stanford.edu [Department of Physics and SITP, Stanford University, Stanford, California 94305 (United States)

    2013-07-01

    We develop a new class of chaotic inflation models with spontaneously broken conformal invariance. Observational consequences of a broad class of such models are stable with respect to strong deformations of the scalar potential. This universality is a critical phenomenon near the point of enhanced symmetry, SO(1,1), in case of conformal inflation. It appears because of the exponential stretching of the moduli space and the resulting exponential flattening of scalar potentials upon switching from the Jordan frame to the Einstein frame in this class of models. This result resembles stretching and flattening of inhomogeneities during inflationary expansion. It has a simple interpretation in terms of velocity versus rapidity near the Kähler cone in the moduli space, similar to the light cone of special theory of relativity. This effect makes inflation possible even in the models with very steep potentials. We describe conformal and superconformal versions of this cosmological attractor mechanism.

  16. The insulin receptor activation process involves localized conformational changes.

    Science.gov (United States)

    Baron, V; Kaliman, P; Gautier, N; Van Obberghen, E

    1992-11-15

    The molecular process by which insulin binding to the receptor alpha-subunit induces activation of the receptor beta-subunit with ensuing substrate phosphorylation remains unclear. In this study, we aimed at approaching this molecular mechanism of signal transduction and at delineating the cytoplasmic domains implied in this process. To do this, we used antipeptide antibodies to the following sequences of the receptor beta-subunit: (i) positions 962-972 in the juxtamembrane domain, (ii) positions 1247-1261 at the end of the kinase domain, and (iii) positions 1294-1317 and (iv) positions 1309-1326, both in the receptor C terminus. We have previously shown that insulin binding to its receptor induces a conformational change in the beta-subunit C terminus. Here, we demonstrate that receptor autophosphorylation induces an additional conformational change. This process appears to be distinct from the one produced by ligand binding and can be detected in at least three different beta-subunit regions: the juxtamembrane domain, the kinase domain, and the C terminus. Hence, the cytoplasmic part of the receptor beta-subunit appears to undergo an extended conformational change upon autophosphorylation. By contrast, the insulin-induced change does not affect the juxtamembrane domain 962-972 nor the kinase domain 1247-1261 and may be limited to the receptor C terminus. Further, we show that the hormone-dependent conformational change is maintained in a kinase-deficient receptor due to a mutation at lysine 1018. Therefore, during receptor activation, the ligand-induced change could precede ATP binding and receptor autophosphorylation. We propose that insulin binding leads to a transient receptor form that may allow ATP binding and, subsequently, autophosphorylation. The second conformational change could unmask substrate-binding sites and stabilize the receptor in an active conformation. PMID:1331080

  17. Conformational biosensors reveal GPCR signalling from endosomes

    DEFF Research Database (Denmark)

    Irannejad, R; Tomshine, Jin C; Tomshine, Jon R;

    2013-01-01

    A long-held tenet of molecular pharmacology is that canonical signal transduction mediated by G-protein-coupled receptor (GPCR) coupling to heterotrimeric G proteins is confined to the plasma membrane. Evidence supporting this traditional view is based on analytical methods that provide limited...... or no subcellular resolution. It has been subsequently proposed that signalling by internalized GPCRs is restricted to G-protein-independent mechanisms such as scaffolding by arrestins, or GPCR activation elicits a discrete form of persistent G protein signalling, or that internalized GPCRs can indeed contribute...... to the acute G-protein-mediated response. Evidence supporting these various latter hypotheses is indirect or subject to alternative interpretation, and it remains unknown if endosome-localized GPCRs are even present in an active form. Here we describe the application of conformation-specific single...

  18. Epigenetic dominance of prion conformers.

    Directory of Open Access Journals (Sweden)

    Eri Saijo

    2013-10-01

    Full Text Available Although they share certain biological properties with nucleic acid based infectious agents, prions, the causative agents of invariably fatal, transmissible neurodegenerative disorders such as bovine spongiform encephalopathy, sheep scrapie, and human Creutzfeldt Jakob disease, propagate by conformational templating of host encoded proteins. Once thought to be unique to these diseases, this mechanism is now recognized as a ubiquitous means of information transfer in biological systems, including other protein misfolding disorders such as those causing Alzheimer's and Parkinson's diseases. To address the poorly understood mechanism by which host prion protein (PrP primary structures interact with distinct prion conformations to influence pathogenesis, we produced transgenic (Tg mice expressing different sheep scrapie susceptibility alleles, varying only at a single amino acid at PrP residue 136. Tg mice expressing ovine PrP with alanine (A at (OvPrP-A136 infected with SSBP/1 scrapie prions propagated a relatively stable (S prion conformation, which accumulated as punctate aggregates in the brain, and produced prolonged incubation times. In contrast, Tg mice expressing OvPrP with valine (V at 136 (OvPrP-V136 infected with the same prions developed disease rapidly, and the converted prion was comprised of an unstable (U, diffusely distributed conformer. Infected Tg mice co-expressing both alleles manifested properties consistent with the U conformer, suggesting a dominant effect resulting from exclusive conversion of OvPrP-V136 but not OvPrP-A136. Surprisingly, however, studies with monoclonal antibody (mAb PRC5, which discriminates OvPrP-A136 from OvPrP-V136, revealed substantial conversion of OvPrP-A136. Moreover, the resulting OvPrP-A136 prion acquired the characteristics of the U conformer. These results, substantiated by in vitro analyses, indicated that co-expression of OvPrP-V136 altered the conversion potential of OvPrP-A136 from the S to

  19. Nonlocal gravity: Conformally flat spacetimes

    CERN Document Server

    Bini, Donato

    2016-01-01

    The field equations of the recent nonlocal generalization of Einstein's theory of gravitation are presented in a form that is reminiscent of general relativity. The implications of the nonlocal field equations are studied in the case of conformally flat spacetimes. Even in this simple case, the field equations are intractable. Therefore, to gain insight into the nature of these equations, we investigate the structure of nonlocal gravity in two-dimensional spacetimes. While any smooth 2D spacetime is conformally flat and satisfies Einstein's field equations, only a subset containing either a Killing vector or a homothetic Killing vector can satisfy the field equations of nonlocal gravity.

  20. Influence of barium substitution on bioactivity, thermal and physico-mechanical properties of bioactive glass

    Energy Technology Data Exchange (ETDEWEB)

    Arepalli, Sampath Kumar, E-mail: askumar.rs.cer11@iitbhu.ac.in; Tripathi, Himanshu; Vyas, Vikash Kumar; Jain, Shubham; Suman, Shyam Kumar; Pyare, Ram; Singh, S.P., E-mail: spsinghceram@gmail.com

    2015-04-01

    Barium with low concentration in the glasses acts as a muscle stimulant and is found in human teeth. We have made a primary study by substituting barium in the bioactive glass. The chemical composition containing (46.1 − X) SiO{sub 2−}–24.3 Na{sub 2}O–26.9 CaO–2.6 P{sub 2}O{sub 5}, where X = 0, 0.4, 0.8, 1.2 and 1.6 mol% of BaO was chosen and melted in an electric furnace at 1400 ± 5 °C. The glasses were characterized to determine their use in biomedical applications. The nucleation and crystallization regimes were determined by DTA and the controlled crystallization was carried out by suitable heat treatment. The crystalline phase formed was identified by using XRD technique. Bioactivity of these glasses was assessed by immersion in simulated body fluid (SBF) for various time periods. The formation of hydroxy carbonate apatite (HCA) layer was identified by FTIR spectrometry, scanning electron microscope (SEM) and XRD which showed the presence of HCA as the main phase in all tested bioactive glass samples. Flexural strength and densities of bioactive glasses have been measured and found to increase with increasing the barium content. The human blood compatibility of the samples was evaluated and found to be pertinent. - Highlights: • In vitro bioactivity of soda-lime–baria-phospho-silicate glass was investigated. • HCA formed on surface of glasses was confirmed by XRD, SEM and FTIR spectrometry. • Mechanical properties of glasses were found to increase with barium addition. • Hemolysis showed that 1.2 mol% BaO bioactive glass exhibited better biocompatibility. • Barium substituted bioactive glasses can be used as bone implants.

  1. SIMS: a hybrid method for rapid conformational analysis.

    Directory of Open Access Journals (Sweden)

    Bryant Gipson

    Full Text Available Proteins are at the root of many biological functions, often performing complex tasks as the result of large changes in their structure. Describing the exact details of these conformational changes, however, remains a central challenge for computational biology due the enormous computational requirements of the problem. This has engendered the development of a rich variety of useful methods designed to answer specific questions at different levels of spatial, temporal, and energetic resolution. These methods fall largely into two classes: physically accurate, but computationally demanding methods and fast, approximate methods. We introduce here a new hybrid modeling tool, the Structured Intuitive Move Selector (sims, designed to bridge the divide between these two classes, while allowing the benefits of both to be seamlessly integrated into a single framework. This is achieved by applying a modern motion planning algorithm, borrowed from the field of robotics, in tandem with a well-established protein modeling library. sims can combine precise energy calculations with approximate or specialized conformational sampling routines to produce rapid, yet accurate, analysis of the large-scale conformational variability of protein systems. Several key advancements are shown, including the abstract use of generically defined moves (conformational sampling methods and an expansive probabilistic conformational exploration. We present three example problems that sims is applied to and demonstrate a rapid solution for each. These include the automatic determination of "active" residues for the hinge-based system Cyanovirin-N, exploring conformational changes involving long-range coordinated motion between non-sequential residues in Ribose-Binding Protein, and the rapid discovery of a transient conformational state of Maltose-Binding Protein, previously only determined by Molecular Dynamics. For all cases we provide energetic validations using well

  2. Predicting protein ligand binding motions with the conformation explorer

    Directory of Open Access Journals (Sweden)

    Flores Samuel C

    2011-10-01

    Full Text Available Abstract Background Knowledge of the structure of proteins bound to known or potential ligands is crucial for biological understanding and drug design. Often the 3D structure of the protein is available in some conformation, but binding the ligand of interest may involve a large scale conformational change which is difficult to predict with existing methods. Results We describe how to generate ligand binding conformations of proteins that move by hinge bending, the largest class of motions. First, we predict the location of the hinge between domains. Second, we apply an Euler rotation to one of the domains about the hinge point. Third, we compute a short-time dynamical trajectory using Molecular Dynamics to equilibrate the protein and ligand and correct unnatural atomic positions. Fourth, we score the generated structures using a novel fitness function which favors closed or holo structures. By iterating the second through fourth steps we systematically minimize the fitness function, thus predicting the conformational change required for small ligand binding for five well studied proteins. Conclusions We demonstrate that the method in most cases successfully predicts the holo conformation given only an apo structure.

  3. Flap Conformations in HIV-1 Protease are Altered by Mutations

    Science.gov (United States)

    Fanucci, Gail; Blackburn, Mandy; Veloro, Angelo; Galiano, Luis; Fangu, Ding; Simmerling, Carlos

    2009-03-01

    HIV-1 protease (PR) is an enzyme that is a major drug target in the treatment of AIDS. Although the structure and function of HIV-1 PR have been studied for over 20 years, questions remain regarding the conformations and dynamics of the β-hairpin turns (flaps) that cover the active site cavity. Distance measurements with pulsed EPR spectroscopy of spin labeled constructs of HIV-1 PR have been used to characterize the flap conformations in the apo and inhibitor bound states. From the most probably distances and the breadth of the distance distribution profiles from analysis of the EPR data, insights regarding the flap conformations and flexibility are gained. The EPR results clearly show how drug pressure selected mutations alter the average conformation of the flaps and the degree of opening of the flaps. Molecular dynamics simulations successfully regenerate the experimentally determined distance distribution profiles, and more importantly, provide structural models for full interpretation of the EPR results. By combining experiment and theory to understand the role that altered flap flexibility/conformations play in the mechanism of drug resistance, key insights are gained toward the rational development of new inhibitors of this important enzyme.

  4. Conformational elasticity can facilitate TALE-DNA recognition.

    Science.gov (United States)

    Lei, Hongxing; Sun, Jiya; Baldwin, Enoch P; Segal, David J; Duan, Yong

    2014-01-01

    Sequence-programmable transcription activator-like effector (TALE) proteins have emerged as a highly efficient tool for genome engineering. Recent crystal structures depict a transition between an open unbound solenoid and more compact DNA-bound solenoid formed by the 34 amino acid repeats. How TALEs switch conformation between these two forms without substantial energetic compensation, and how the repeat-variable di-residues (RVDs) discriminate between the cognate base and other bases still remain unclear. Computational analysis on these two aspects of TALE-DNA interaction mechanism has been conducted in order to achieve a better understanding of the energetics. High elasticity was observed in the molecular dynamics simulations of DNA-free TALE structure that started from the bound conformation where it sampled a wide range of conformations including the experimentally determined apo and bound conformations. This elastic feature was also observed in the simulations starting from the apo form which suggests low free energy barrier between the two conformations and small compensation required upon binding. To analyze binding specificity, we performed free energy calculations of various combinations of RVDs and bases using Poisson-Boltzmann surface area (PBSA) and other approaches. The PBSA calculations indicated that the native RVD-base structures had lower binding free energy than mismatched structures for most of the RVDs examined. Our theoretical analyses provided new insight on the dynamics and energetics of TALE-DNA binding mechanism.

  5. Physiological removal of silicon from bioactive glass

    Energy Technology Data Exchange (ETDEWEB)

    Lai, W. [Pennsylvania Univ., Philadelphia, PA (United States). Dept. of Bioengineering; Garino, J. [Pennsylvania Univ., Philadelphia, PA (United States). Dept. of Orthopaedic Surgery; Flaitz, C.M. [Texas Univ., Houston, TX (United States). Div. of Oral and Maxillofacial Pathology; Ducheyne, P. [Pennsylvania Univ., Philadelphia, PA (United States). Dept. of Bioengineering; Pennsylvania Univ., Philadelphia, PA (United States). Dept. of Orthopaedic Surgery

    2001-07-01

    Bioactive glass granules were implanted in the paraspinal muscle and tibiae of rabbits in order to determine the pathway of the silicon released from bioactive glass in vivo. We traced and quantified the silicon released by obtaining 24-hour urine samples, as well as blood samples for up to 7 months after implantation. Furthermore, local muscle and bone tissue as well as the following organs were resected for chemical and histopathological analyses: brain, heart, kidney, liver, lung, lymph nodes, spleen, and thymus. The concentrations of silicon found in the urine were well below saturation and no accumulation of silicon was found in the major organs after silicon excretion had halted. The removal of silicon from the body matrix was slower overall compared to an intramuscular site, taking a total of 24 weeks versus 19 weeks to complete silicon removal, respectively. (orig.)

  6. Bioactivity of mica/apatite glass ceramics

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The bioactivity of mica/apatite glass ceramic composites, including the in vitro behavior in simulated body fluid and the histological appearance of the interface between the mica/apatite glass ceramics and the rabbit mandible defect in vivo under a dynamic condition. The results show that biological apatite layer forms on the surface of the mica/apatite glass ceramics after 1 d of immersion in the simulated body fluid, and becomes dense after 14 d. In vivo tests indicate that bone formation occurs after implantation for 14 d, and strong bonding of bone to the implant occurs after 42 d. No aseptic loosening occurs during 42 d of implantation. The finding shows that mica/apatite glass ceramics have good bioactivity and osteoconductivity for constructing bone graft, and can be promising for biomedical application.

  7. Bioactive foods and ingredients for health.

    Science.gov (United States)

    Weaver, Connie M

    2014-05-01

    Bioactive compounds in foods have been gaining interest, and processes to consider them for public health recommendations are being discussed. However, the evidence base is difficult to assemble. It is difficult to demonstrate causality, and there often is not a single compound-single effect relation. Furthermore, health benefits may be due to metabolites produced by the host or gut microbiome rather than the food constituent per se. Properties that can be measured in a food may not translate to in vivo health effects. Compounds that are being pursued may increase gut microbial diversity, improve endothelial function, improve cognitive function, reduce bone loss, and so forth. A new type of bioactive component is emerging from epigenetic modifications by our diet, including microRNA transfer from our diet, which can regulate expression of human genes. Policy processes are needed to establish the level of evidence needed to determine dietary advice and policy recommendations and to set research agendas.

  8. Temperature: Human Regulating, Ants Conforming

    Science.gov (United States)

    Clopton, Joe R.

    2007-01-01

    Biological processes speed up as temperature rises. Procedures for demonstrating this with ants traveling on trails, and data gathered by students on the Argentine ant ("Linepithema humile") are presented. The concepts of temperature regulation and conformity are detailed with a focus on the processes rather than on terms that label the organisms.

  9. Defects in conformal field theory

    Science.gov (United States)

    Billò, Marco; Gonçalves, Vasco; Lauria, Edoardo; Meineri, Marco

    2016-04-01

    We discuss consequences of the breaking of conformal symmetry by a flat or spherical extended operator. We adapt the embedding formalism to the study of correlation functions of symmetric traceless tensors in the presence of the defect. Two-point functions of a bulk and a defect primary are fixed by conformal invariance up to a set of OPE coefficients, and we identify the allowed tensor structures. A correlator of two bulk primaries depends on two cross-ratios, and we study its conformal block decomposition in the case of external scalars. The Casimir equation in the defect channel reduces to a hypergeometric equation, while the bulk channel blocks are recursively determined in the light-cone limit. In the special case of a defect of codimension two, we map the Casimir equation in the bulk channel to the one of a four-point function without defect. Finally, we analyze the contact terms of the stress-tensor with the extended operator, and we deduce constraints on the CFT data. In two dimensions, we relate the displacement operator, which appears among the contact terms, to the reflection coefficient of a conformal interface, and we find unitarity bounds for the latter.

  10. Boundary Logarithmic Conformal Field Theory

    CERN Document Server

    Kogan, I I; Kogan, Ian I.; Wheater, John F.

    2000-01-01

    We discuss the effect of boundaries in boundary logarithmic conformal field theory and show, with reference to both $c=-2$ and $c=0$ models, how they produce new features even in bulk correlation functions which are not present in the corresponding models without boundaries. We show how Cardy's relation between boundary states and bulk quantities is modified.

  11. Bioactive Compounds from Marine Bacteria and Fungi

    OpenAIRE

    Debbab, Abdessamad; Aly, Amal H.; Lin, Wen H.; Proksch, Peter

    2010-01-01

    Summary Marine bacteria and fungi are of considerable importance as new promising sources of a huge number of biologically active products. Some of these marine species live in a stressful habitat, under cold, lightless and high pressure conditions. Surprisingly, a large number of species with high diversity survive under such conditions and produce fascinating and structurally complex natural products. Up till now, only a small number of microorganisms have been investigated for bioactive me...

  12. Bioactive Compounds Found in Brazilian Cerrado Fruits

    OpenAIRE

    Elisa Flávia Luiz Cardoso Bailão; Ivano Alessandro Devilla; Edemilson Cardoso da Conceição; Leonardo Luiz Borges

    2015-01-01

    Functional foods include any natural product that presents health-promoting effects, thereby reducing the risk of chronic diseases. Cerrado fruits are considered a source of bioactive substances, mainly phenolic compounds, making them important functional foods. Despite this, the losses of natural vegetation in the Cerrado are progressive. Hence, the knowledge propagation about the importance of the species found in Cerrado could contribute to the preservation of this biome. This review provi...

  13. Purification, structure and function of bioactive peptides

    OpenAIRE

    Eriste, Elo

    2004-01-01

    Peptides are vitally important molecules and many evoke cellular responses. The completion of several genome sequencing projects has revealed a number of new genes. However, as functional peptides often contain posttranslational modifications and/or occur at various lengths, it is of great importance to detect, purify and characterize novel bioactive peptides. To achieve these goals, new methods for peptide detection, isolation and functional characterization have to be d...

  14. Nanoencapsulation of bioactive compounds for food applications

    OpenAIRE

    Sessa, Mariarenata

    2012-01-01

    2010 - 2011 The increase in dietary-intake-related illnesses, such as obesity, cardiovascular diseases, hypertension, diabetes and cancer, have made in recent years the development of health-and-wellness promoting foods a priority of the food industry. Clinical studies have demonstrated tangible health benefits that may be derived from the intake of bioactive compounds. However many difficulties are associated with their inclusion in food matrices, due to a very low solubility in water and...

  15. Fluoride-containing bioactive glasses: Glass design, structure, bioactivity, cellular interactions, and recent developments.

    Science.gov (United States)

    Shah, Furqan A

    2016-01-01

    Bioactive glasses (BGs) are known to bond to both hard and soft tissues. Upon exposure to an aqueous environment, BG undergoes ion exchange, hydrolysis, selective dissolution and precipitation of an apatite layer on their surface, which elicits an interfacial biological response resulting in bioactive fixation, inhibiting further dissolution of the glass, and preventing complete resorption of the material. Fluorine is considered one of the most effective in-vivo bone anabolic factors. In low concentrations, fluoride ions (F(-)) increase bone mass and mineral density, improve the resistance of the apatite structure to acid attack, and have well documented antibacterial properties. F(-) ions may be incorporated into the glass in the form of calcium fluoride (CaF2) either by part-substitution of network modifier oxides, or by maintaining the ratios of the other constituents relatively constant. Fluoride-containing bioactive glasses (FBGs) enhance and control osteoblast proliferation, differentiation and mineralisation. And with their ability to release fluoride locally, FBGs make interesting candidates for various clinical applications, dentinal tubule occlusion in the treatment of dentin hypersensitivity. This paper reviews the chemistry of FBGs and the influence of F(-) incorporation on the thermal properties, bioactivity, and cytotoxicity; and novel glass compositions for improved mechanical properties, processing, and bioactive potential.

  16. A mathematical model for predicting controlled release of bioactive agents from composite fiber structures.

    Science.gov (United States)

    Zilberman, Meital; Sofer, Moran

    2007-03-01

    A mathematical model for predicting bioactive agent release profiles from core/shell fiber structures was developed and studied. These new composite fibers, which combine good mechanical properties with desired protein release profiles, are designed for use in tissue regeneration and other biomedical applications. These fibers are composed of an inner dense polymeric core surrounded by a porous bioresorbable shell, which encapsulates the bioactive agent molecules. The model is based on Fick's second law of diffusion, and on two major assumptions: (a) first-order degradation kinetics of the porous shell, and (b) a nonconstant diffusion coefficient for the bioactive agent, which increases with time because of degradation of the host polymer. Three factors are evaluated and included in this model: a porosity factor, a tortuosity factor, and a polymer concentration factor. Our study indicates that the model correlates well with in vitro release results, exhibiting a mean error of less than 2.2% for most studied cases. In this study, the model was used for predicting protein release profiles from fibers with shells of various initial molecular weights and for predicting the release of proteins with various molecular weights. This new model exhibits a potential for simulating fibrous systems for a wide variety of biomedical applications. PMID:17072845

  17. Turnover mechanisms of organic conformation on turbidity in drinking water

    Institute of Scientific and Technical Information of China (English)

    ZHONG Runsheng; ZHU Chunwei; ZHANG Xihui; GUAN Yuntao

    2007-01-01

    The turbidity variation in artificial water and samples from a water plant was investigated in the presence of organics with different relative molecular mass.The results show that recessive turbidity existed when water chemical conditions were changing.The formation of turbidity depended on organic relative molecular mass and their conformations on particles.At higher pH and lower ionic strength,the organic chains with a more extended conformation resulted in rising turbidity of the suspension.At lower pH,the reconformarion of organics took place due to charge neutralization by the proton,resulting in a decline in turbidity.The addition of NaCl and MgCl2 at pH 7.00 also resulted in a decrease of turbidity in the suspension.It is believed that the occurrence of recessive turbidity has a significant influence on the stability of water supply quality.

  18. A new bio-active glass ceramic

    International Nuclear Information System (INIS)

    Since 1960 fine ceramics such as alumina have been used side by side with metallic materials for bone and joint replacement. They have high mechanical strength and are free from corrosion problem faced by metals. However they don't bond to the natural living bone and hence are called bio-inactive. This was followed by the development of bio-active glasses and glass-ceramics which bond to the natural bone but have low mechanical strength. In the present work a new bio-active glass-ceramic, based on CaO-SiO/sub 2/-P/sub 2/O/sub 3/-MgO composition, has been developed which has mechanical strength compared to that of a bio-inactive glass ceramic and also bonds strongly to the natural bone. X-ray diffraction analysis reveals wollastanite and apatite phases in the glass ceramic. A new bio-active cement has also been developed which can be used to join broken pieces of bone or by itself at a filler. (author)

  19. Are bioactive-rich fractions functionally richer?

    Science.gov (United States)

    Imam, Mustapha Umar; Ismail, Maznah; Ooi, Der Jiun; Azmi, Nur Hanisah; Sarega, Nadarajan; Chan, Kim Wei; Bhanger, Muhammad Iqbal

    2016-08-01

    Plant bioresources are relied upon as natural, inexpensive, and sustainable remedies for the management of several chronic diseases worldwide. Plants have historically been consumed for medicinal purposes based on traditional belief, but this trend is currently changing. The growing interest in the medicinal properties of plant bioresources stems from concerns of side effects and other adverse effects caused by synthetic drugs. This interest has yielded a better understanding of the roles of plant bioactive compounds in health promotion and disease prevention, including the underlying mechanisms involved in such functional effects. The desire to maximize the potential of phytochemicals has led to the development of "rich fractions," in which extracts contain bioactive compounds in addition to elevated levels of the primary compound. Although a rich fraction effectively increases the bioactivity of the extract, the standardization and quality assurance process can be challenging. However, the supercritical fluid extraction (SFE) system is a promising green technology in this regard. Future clinical and pharmacological studies are needed to fully elucidate the implications of these preparations in the management of human diseases, thereby fostering a move toward evidence-based medicine. PMID:25641328

  20. Transfersomes: self-optimizing carriers for bioactives.

    Science.gov (United States)

    Rai, Kavita; Gupta, Yashwant; Jain, Anekant; Jain, Sanjay K

    2008-01-01

    The transdermal route of drug delivery has gained great interest of pharmaceutical research, as it circumvents number of problems associated with oral route of drug administration. The major barrier in transdermal delivery of drug is the skin intrinsic barrier, the stratum corneum, the outermost envelop of the skin that offers the principal hurdle for diffusion of hydrophilic ionizable bioactives. Recently, various strategies have been used to augment the transdermal delivery of bioactives. Mainly, they include iontophoresis, electrophoresis, sonophoresis, chemical permeation enhancers, microneedles, and vesicular system (liposomes, niosomes, elastic liposomes such as ethosomes and transfersomes). Among these strategies transferosomes appear promising. Transport of this vesicular system through skin and epithelial hurdle depends upon the flexibility of their membrane, which can be attained using appropriate ratio of surfactant. Transfersomes have shown immense potential in drug delivery across the skin. Recent success also demonstrates the potential of transfersome in vaccine, steroid, protein, and peptide delivery across the skin. It is also used for transporting genetic material and achieving transfection. This review highlights the various aspects of the transferosomes in the effective delivery of drug/bioactives across the skin. PMID:19055232

  1. Conformational re-analysis of (+)-meptazinol: an opioid with mixed analgesic pharmacophores

    Institute of Scientific and Technical Information of China (English)

    Wei LI; Xing-hai WANG; Choi-wan LAU; Yun TANG; Qiong XIE; Zhui-bai QIU

    2006-01-01

    Aim: To further investigate the analgesic pharmacophore of (+)-meptazinol. Methods: Two different opioid pharmacophores, Pharm-Ⅰ and Pharm-Ⅱ, were established from structures of nine typical opiates and meperidine by using molecular modeling approaches according to their different structure activity relationship properties. They were further validated by a set of conformationally constrained arylpiperidines. Two conformers of (+)-meptazinol (Conformer-Ⅰ and Con-former-Ⅱ) detected in solution were then fitted into the pharmacophores, respectively, by Fit Atoms facilities available in SYBYL, a computational modeling tool kit for molecular design and analysis. Results: Conformer-Ⅰ fit Pharm-Ⅰ from typical opiates well. However, Conformer-Ⅱ fit none of these pharmacophores. Instead, it was found to be similar to another potent analgesic, benzofuro[2,3-c] pyridin-6-ol, whose pharmacophore was suggested to hold the transitional state between the two established pharmacophores. Unlike typical analgesics derived from 4-aryl piperidine (eg, meperidine) with one conformer absolutely overwhelming, the (+)-meptazinol exists in two conformers with similar amounts in solution. Furthermore, both conformers can not transform to each other freely in ordinary conditions based on our NMR results. Conclusion: (+)-meptazinol was suggested to be an opioid with mixed analgesic pharmacophores, which may account for the complicated pharmacological properties of meptazinol.

  2. Conformational States of Melittin at a Bilayer Interface

    OpenAIRE

    Andersson, Magnus; Ulmschneider, Jakob P.; Ulmschneider, Martin B.; White, Stephen H.

    2013-01-01

    The distribution of peptide conformations in the membrane interface is central to partitioning energetics. Molecular-dynamics simulations enable characterization of in-membrane structural dynamics. Here, we describe melittin partitioning into dioleoylphosphatidylcholine lipids using CHARMM and OPLS force fields. Although the OPLS simulation failed to reproduce experimental results, the CHARMM simulation reported was consistent with experiments. The CHARMM simulation showed melittin to be repr...

  3. The puzzle of bond length variation in substituted cyclobutenes. A new example: molecular structure and conformations of 1,2-dimethoxy-3,3,4,4-tetrafluorocyclobut-1-ene.

    Science.gov (United States)

    Richardson, Alan D; Hedberg, Kenneth; Lunelli, Bruno

    2010-04-29

    The structure and composition of 1,2-dimethoxy-3,3,4,4-tetrafluorocyclobut-1-ene (DMCB) have been measured by electron diffraction from the gas at a temperature of 370 K with the help of auxiliary data from molecular orbital and normal coordinate calculations, the former at several levels of theory and basis-set size, most importantly B3LYP/cc-pVTZ. The compound was found to exist primarily as a rotamer of C(s) symmetry (ca. 98%; 2sigma = 11%) with the remainder one of C(2v) symmetry; theory predicts about 88% C(s). Values for some of the more important parameters (r(g)/A; angle(alpha)/deg) of the C(s) form are r(C=C) = 1.337(21), r(C1-C4) = 1.496(8), r(C2-C3) = 1.501(8), r(C3-C4) = 1.567(12), r(C1-O) = 1.318(12), r(C2-O) = 1.340(12), r(C3-F) = 1.375(4), r(C4-F) = 1.368(4), angle(ave)(C=C-C) = 94.4(4), angle(ave)(C=C-O) = 133.5(12), angle(ave)(C-O-C) = 119.6(13), and angle(ave)(F-C-F) = 104.4(7). Surprisingly, although electron-diffraction values for the fluorinated C3-C4 bond in other cyclobutenes are greater than that for cyclobutene itself, that is not the case for DMCB where it is found to be about the same. Details of the DMCB structure, together with possible reasons for the observed variations in the length of the C3-C4 bond in fluorinated cyclobutene-like molecules, are discussed.

  4. An experimental and theoretical investigation of Acenaphthene-5-boronic acid: Conformational study, NBO and NLO analysis, molecular structure and FT-IR, FT-Raman, NMR and UV spectra

    Science.gov (United States)

    Karabacak, Mehmet; Sinha, Leena; Prasad, Onkar; Asiri, Abdullah M.; Cinar, Mehmet

    2013-11-01

    The solid state Fourier transform infrared (FT-IR) and FT-Raman spectra of Acenaphthene-5-boronic acid (AN-5-BA), have been recorded in the range 4000-400 cm-1 and 4000-10 cm-1, respectively. Density functional theory (DFT), with the B3LYP functional was used for the optimization of the ground state geometry and simulation of the infrared and Raman spectra of the molecule. The vibrational wave numbers and their assignments were examined theoretically using the Gaussian 09 set of quantum chemistry codes and the normal modes were assigned by a scaled quantum mechanical (SQM) force field approach. Hydrogen-bonded dimer of AN-5-BA, optimized by counterpoise correction, has also been studied by B3LYP at the 6-311++G(d,p) level and the effects of molecular association through O-H⋯O hydrogen bonding have been discussed. The 1H and 13C nuclear magnetic resonance (NMR) chemical shifts of the molecule were calculated by Gauge-Including Atomic Orbital (GIAO) method. Natural bond orbital (NBO) analysis has been applied to study stability of the molecule arising from charge delocalization. UV spectrum of the title compound was also recorded and the electronic properties, such as frontier orbitals, and band gap energies were measured by TD-DFT approach. The first order hyperpolarizability , its components and associated properties such as average polarizability and anisotropy of the polarizability (α and Δα) of AN-5-BA was calculated using the finite-field approach.

  5. Fake conformal symmetry in unimodular gravity

    Science.gov (United States)

    Oda, Ichiro

    2016-08-01

    We study Weyl symmetry (local conformal symmetry) in unimodular gravity. It is shown that the Noether currents for both Weyl symmetry and global scale symmetry vanish exactly as in conformally invariant scalar-tensor gravity. We clearly explain why in the class of conformally invariant gravitational theories, the Noether currents vanish by starting with conformally invariant scalar-tensor gravity. Moreover, we comment on both classical and quantum-mechanical equivalences in Einstein's general relativity, conformally invariant scalar-tensor gravity, and the Weyl-transverse gravity. Finally, we discuss the Weyl current in the conformally invariant scalar action and see that it is also vanishing.

  6. Natural Phyto-Bioactive Compounds for the Treatment of Type 2 Diabetes: Inflammation as a Target

    Science.gov (United States)

    Gothai, Sivapragasam; Ganesan, Palanivel; Park, Shin-Young; Fakurazi, Sharida; Choi, Dong-Kug; Arulselvan, Palanisamy

    2016-01-01

    Diabetes is a metabolic, endocrine disorder which is characterized by hyperglycemia and glucose intolerance due to insulin resistance. Extensive research has confirmed that inflammation is closely involved in the pathogenesis of diabetes and its complications. Patients with diabetes display typical features of an inflammatory process characterized by the presence of cytokines, immune cell infiltration, impaired function and tissue destruction. Numerous anti-diabetic drugs are often prescribed to diabetic patients, to reduce the risk of diabetes through modulation of inflammation. However, those anti-diabetic drugs are often not successful as a result of side effects; therefore, researchers are searching for efficient natural therapeutic targets with less or no side effects. Natural products’ derived bioactive molecules have been proven to improve insulin resistance and associated complications through suppression of inflammatory signaling pathways. In this review article, we described the extraction, isolation and identification of bioactive compounds and its molecular mechanisms in the prevention of diabetes associated complications. PMID:27527213

  7. EFFECTS OF INCORPORATING NATURAL MINERALS ON PRODUCTION AND BIOACTIVITY OF BIOACTIVE GLASS CERAMICS

    Directory of Open Access Journals (Sweden)

    Franco Matias Stabile

    2016-07-01

    Full Text Available Two glass-ceramics composition were produced from natural minerals. Quartzes and feldspars were pre-selected on the basis of their purities studied by X-ray diffraction (XRD and chemical analysis. Prepared compositions of glasses precursors were two different theoretical leucite (KAlSi₂O₆ /Bioglass 45S5 (L/Bg ratios. Transformations of raw materials mixtures and glass precursors were studied by differential thermal analyses. On the basis of thermal analysis results, glass ceramics were produced and characterized by XRD. Glass-ceramics were composed of two major crystalline phases, leucite and sodium calcium silicate. Bioactivity tests were performed submerging the glass-ceramics into simulated body fluid (SBF for different periods (1, 5 and 10 days. Bioactive behavior was monitored by XRD and scanning electron microscopy (SEM. Studied samples were found to be bioactive, in which hydroxyapatite layer was developed within 5 days of contact with SBF.

  8. Probing insulin bioactivity in oral nanoparticles produced by ultrasonication-assisted emulsification/internal gelation

    Directory of Open Access Journals (Sweden)

    Lopes MA

    2015-09-01

    Full Text Available Marlene A Lopes,1,2,* Bárbara Abrahim-Vieira,3,* Claudia Oliveira,4,5 Pedro Fonte,6,7 Alessandra M T Souza,3 Tammy Lira,3 Joana A D Sequeira,1,2 Carlos R Rodrigues,3 Lúcio M Cabral,3 Bruno Sarmento,6–8 Raquel Seiça,9 Francisco Veiga,1,2 António J Ribeiro1,4,5 1Faculty of Pharmacy, University of Coimbra, Coimbra, Portugal; 2CNC – Center for Neuroscience and Cell Biology, Coimbra, Portugal; 3Department of Pharmaceutics, Faculty of Pharmacy, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 4I3S, Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal; 5Group Genetics of Cognitive Dysfunction, IBMC – Instituto de Biologia Molecular e Celular, Porto, Portugal; 6REQUIMTE, Department of Chemical Sciences – Applied Chemistry Lab, Faculty of Pharmacy, University of Porto, Porto, Portugal; 7CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Gandra, Portugal; 8INEB – Instituto de Engenharia Biomédica, University of Porto, Porto, Portugal; 9IBILI – Institute of Biomedical Research in Light and Image, Faculty of Medicine, University of Coimbra, Coimbra, Portugal *These authors contributed equally to this work Abstract: Alginate–dextran sulfate-based particles obtained by emulsification/internal gelation technology can be considered suitable carriers for oral insulin delivery. A rational study focused on the emulsification and particle recovery steps was developed in order to reduce particles to the nanosize range while keeping insulin bioactivity. There was a decrease in size when ultrasonication was used during emulsification, which was more pronounced when a cosurfactant was added. Ultrasonication add-on after particle recovery decreased aggregation and led to a narrower nanoscale particle-size distribution. Insulin encapsulation efficiency was 99.3%±0.5%, attributed to the strong pH-stabilizing electrostatic effect between insulin and

  9. Conformal Gravity rotation curves with a conformal Higgs halo

    Science.gov (United States)

    Horne, Keith

    2016-06-01

    We discuss the effect of a conformally coupled Higgs field on conformal gravity (CG) predictions for the rotation curves of galaxies. The Mannheim-Kazanas (MK) metric is a valid vacuum solution of CG's fourth-order Poisson equation if and only if the Higgs field has a particular radial profile, S(r) = S0 a/(r + a), decreasing from S0 at r = 0 with radial scalelength a. Since particle rest masses scale with S(r)/S0, their world lines do not follow time-like geodesics of the MK metric gμν, as previously assumed, but rather those of the Higgs-frame MK metric tilde{g}_{μ ν }=Ω ^2 g_{μ ν }, with the conformal factor Ω(r) = S(r)/S0. We show that the required stretching of the MK metric exactly cancels the linear potential that has been invoked to fit galaxy rotation curves without dark matter. We also formulate, for spherical structures with a Higgs halo S(r), the CG equations that must be solved for viable astrophysical tests of CG using galaxy and cluster dynamics and lensing.

  10. The interplay of solvation, molecular conformation and supramolecular assembly in 1,1'-({[(ethane-1,2-diyl)dioxy](1,2-phenylene)}bis(methanylylidene))bis(thiosemicarbazide) and its N,N-dimethylformamide disolvate.

    Science.gov (United States)

    Mohamed, Shaaban K; Younes, Sabry H H; Abdel-Raheem, Eman M M; Mague, Joel T; Akkurt, Mehmet; Glidewell, Christopher

    2015-11-01

    The wide diversity of applications of thiosemicarbazones and bis(thiosemicarbazones) has seen them used as anticancer and antitubercular agents, and as ligands in metal complexes designed to act as site-specific radiopharmaceuticals. Molecules of 1,1'-({[(ethane-1,2-diyl)dioxy](1,2-phenylene)}bis(methanylylidene))bis(thiosemicarbazide) {alternative name: 2,2'-[ethane-1,2-diylbis(oxy)]dibenzaldehyde bis(thiosemicarbazide)}, C18H20N6O2S2, (I), lie across twofold rotation axes in the space group C2/c, with an O-C-C-O torsion angle of -59.62 (13)° and a trans-planar arrangement of the thiosemicarbazide fragments relative to the adjacent aryl rings. The molecules of (I) are linked by N-H...S hydrogen bonds to form sheets containing R(2)4(38) rings and two types of R(2)2(8) ring. In the N,N-dimethylformamide disolvate, C18H20N6O2S2·2C3H7NO, (II), the independent molecular components all lie in general positions, but one of the solvent molecules is disordered over two sets of atomic sites having occupancies of 0.839 (3) and 0.161 (3). The O-C-C-O torsion angle in the ArOCH2CH2OAr component is -75.91 (14)° and the independent thiosemicarbazide fragments both adopt a cis-planar arrangement relative to the adjacent aryl rings. The ArOCH2CH2OAr components in (II) are linked by N-H...S hydrogen bonds to form deeply puckered sheets containing R(2)2(8), R(2)4(8) and two types of R(2)2(38) rings, and which contain cavities which accommodate all of the solvent molecules in the interior of the sheets. Comparisons are made with some related compounds. PMID:26524167

  11. Conformational heterogeneity of the calmodulin binding interface

    Science.gov (United States)

    Shukla, Diwakar; Peck, Ariana; Pande, Vijay S.

    2016-04-01

    Calmodulin (CaM) is a ubiquitous Ca2+ sensor and a crucial signalling hub in many pathways aberrantly activated in disease. However, the mechanistic basis of its ability to bind diverse signalling molecules including G-protein-coupled receptors, ion channels and kinases remains poorly understood. Here we harness the high resolution of molecular dynamics simulations and the analytical power of Markov state models to dissect the molecular underpinnings of CaM binding diversity. Our computational model indicates that in the absence of Ca2+, sub-states in the folded ensemble of CaM's C-terminal domain present chemically and sterically distinct topologies that may facilitate conformational selection. Furthermore, we find that local unfolding is off-pathway for the exchange process relevant for peptide binding, in contrast to prior hypotheses that unfolding might account for binding diversity. Finally, our model predicts a novel binding interface that is well-populated in the Ca2+-bound regime and, thus, a candidate for pharmacological intervention.

  12. Mannich reaction: A versatile and convenient approach to bioactive skeletons

    Indian Academy of Sciences (India)

    Selva Ganesan Subramaniapillai

    2013-05-01

    This review gives an insight into the recent applications of Mannich reaction and its variants in the construction of bioactive molecules. Emphasis is given to the Mannich reaction that provides bioactive molecules and/or modifies the property of an existing bioactive molecule. The role of Mannich reaction in the construction of antimalarial, antitumour, antimicrobial, antitubercular, antiinflammatory and anticonvulsant molecules and also the significance of aminoalkyl Mannich side chain on the biological property of molecules is discussed here.

  13. Conformal invariance in the quantum field theory

    International Nuclear Information System (INIS)

    Basic features concerning the present knowledge of conformal symmetry are illustrated in a simple model. Composite field dimensions of this model are computed and related to the conformal group. (author)

  14. Conformal methods in general relativity

    CERN Document Server

    Valiente Kroon, Juan A

    2016-01-01

    This book offers a systematic exposition of conformal methods and how they can be used to study the global properties of solutions to the equations of Einstein's theory of gravity. It shows that combining these ideas with differential geometry can elucidate the existence and stability of the basic solutions of the theory. Introducing the differential geometric, spinorial and PDE background required to gain a deep understanding of conformal methods, this text provides an accessible account of key results in mathematical relativity over the last thirty years, including the stability of de Sitter and Minkowski spacetimes. For graduate students and researchers, this self-contained account includes useful visual models to help the reader grasp abstract concepts and a list of further reading, making this the perfect reference companion on the topic.

  15. Conformal gravity and "gravitational bubbles"

    CERN Document Server

    Berezin, V A; Eroshenko, Yu N

    2015-01-01

    We describe the general structure of the spherically symmetric solutions in the Weyl conformal gravity. The corresponding Bach equations are derived for the special type of metrics, which can be considered as the representative of the general class. The complete set of the pure vacuum solutions, consisting of two classes, is found. The first one contains the solutions with constant two-dimensional curvature scalar, and the representatives are the famous Robertson--Walker metrics. We called one of them the "gravitational bubbles", which is compact and with zero Weyl tensor. These "gravitational bubbles" are the pure vacuum curved space-times (without any material sources, including the cosmological constant), which are absolutely impossible in General Relativity. This phenomenon makes it easier to create the universe from "nothing". The second class consists of the solutions with varying curvature scalar. We found its representative as the one-parameter family, which can be conformally covered by the thee-para...

  16. Conformal Bootstrap in Mellin Space

    CERN Document Server

    Gopakumar, Rajesh; Sen, Kallol; Sinha, Aninda

    2016-01-01

    We propose a new approach towards analytically solving for the dynamical content of Conformal Field Theories (CFTs) using the bootstrap philosophy. This combines the original bootstrap idea of Polyakov with the modern technology of the Mellin representation of CFT amplitudes. We employ exchange Witten diagrams with built in crossing symmetry as our basic building blocks rather than the conventional conformal blocks in a particular channel. Demanding consistency with the operator product expansion (OPE) implies an infinite set of constraints on operator dimensions and OPE coefficients. We illustrate the power of this method in the epsilon expansion of the Wilson-Fisher fixed point by computing operator dimensions and, strikingly, OPE coefficients to higher orders in epsilon than currently available using other analytic techniques (including Feynman diagram calculations). Our results enable us to get a somewhat better agreement of certain observables in the 3d Ising model, with the precise numerical values that...

  17. History and trends of bioactive glass-ceramics.

    Science.gov (United States)

    Montazerian, Maziar; Dutra Zanotto, Edgar

    2016-05-01

    The interest around bioactive glass-ceramics (GCs) has grown significantly over the last two decades due to their appropriate biochemical and mechanical properties. The intense research effort in this field has led to some new commercial products for biomedical applications. This review article begins with the basic concepts of GC processing and development via controlled heat treatments of monolithic pieces or sinter-crystallization of powdered glasses. We then go on to describe the processing, properties, and applications of some commercial bioactive GCs and discuss selected valuable reported researches on several promising types of bioactive GCs. The article finishes with a section on open relevant research directions for bioactive GC development.

  18. Bioactive Peptides from Muscle Sources: Meat and Fish

    Directory of Open Access Journals (Sweden)

    Catherine Stanton

    2011-08-01

    Full Text Available Bioactive peptides have been identified in a range of foods, including plant, milk and muscle, e.g., beef, chicken, pork and fish muscle proteins. Bioactive peptides from food proteins offer major potential for incorporation into functional foods and nutraceuticals. The aim of this paper is to present an outline of the bioactive peptides identified in the muscle protein of meat to date, with a focus on muscle protein from domestic animals and fish. The majority of research on bioactives from meat sources has focused on angiotensin-1-converting enzyme (ACE inhibitory and antioxidant peptides.

  19. Conformal Transformations and Accelerated Cosmologies

    OpenAIRE

    Crooks, James L.; Frampton, Paul H.

    2006-01-01

    A cosmological theory that predicts a late-time accelerated attractor with a constant dark matter to dark energy ratio can be said to solve the Coincidence Problem. Such cosmologies are naturally generated in the context of non-standard gravity theories under conformal transformation because of the resulting couplings between scalar fields and matter. The present work examines four classes of these transformed theories and finds that only a small subset--those with a single scalar field--are ...

  20. Conformal symmetries in warped manifolds

    Energy Technology Data Exchange (ETDEWEB)

    Apostolopoulos, P S [University of Athens, Department of Physics, Nuclear and Particle Physics Section, Panepistimiopolis, Zografos 15771, Athens (Greece); Carot, J G [Departament de Fisica, Universitat de les Illes Balears, Cra. Valldemossa km 7.5, E-07122 Palma de Mallorca (Spain)

    2005-01-01

    The existence of a Conformal Vector Field (CVF) is studied in the important class of warped manifolds of arbitrary dimension generalizing in this way the corresponding results of the four dimensional geometries. As a concrete example we apply the geometric results in the case of brane-world scenarios when the bulk geometry admits a hypersurface orthogonal Killing Vector Field (KVF) and is filled with a perfect fluid matter content.