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Docking Calculations (docking + calculation)
Selected AbstractsStudy of a highly accurate and fast protein,ligand docking method based on molecular dynamicsCONCURRENCY AND COMPUTATION: PRACTICE & EXPERIENCE, Issue 14 2005M. Taufer Abstract Few methods use molecular dynamics simulations in concert with atomically detailed force fields to perform protein,ligand docking calculations because they are considered too time demanding, despite their accuracy. In this paper we present a docking algorithm based on molecular dynamics which has a highly flexible computational granularity. We compare the accuracy and the time required with well-known, commonly used docking methods such as AutoDock, DOCK, FlexX, ICM, and GOLD. We show that our algorithm is accurate, fast and, because of its flexibility, applicable even to loosely coupled distributed systems such as desktop Grids for docking. Copyright © 2005 John Wiley & Sons, Ltd. [source] NMR Investigation of the Bound Conformation of Natural and Synthetic Oligomannosides to Banana LectinEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 10 2007Caroline Clavel Abstract The conformational behaviour of three mannose-containing oligosaccharides, namely, the ,1,3[,1,6] trisaccharide, a heptasaccharide with ,1,2, ,1,3 and ,1,6 linkages and a tetrasaccharide consisting of ,1,3 and ,1,2 linkages, when bound to banana lectin (BanLec) has been evaluated by trNOE NMR methods and docking calculations. It was found that the molecular recognition event involves a conformational selection process with only one of the conformations present in the free state of the sugar being recognised at the lectin binding site. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Exploring the primary electron acceptor (QA)-site of the bacterial reaction center from Rhodobacter sphaeroidesFEBS JOURNAL, Issue 4 2002Binding mode of vitamin K derivatives The functional replacement of the primary ubiquinone (QA) in the photosynthetic reaction center (RC) from Rhodobacter sphaeroides with synthetic vitamin K derivatives has provided a powerful tool to investigate the electron transfer mechanism. To investigate the binding mode of these quinones to the QA binding site we have determined the binding free energy and charge recombination rate from QA, to D+ (kAD) of 29 different 1,4-naphthoquinone derivatives with systematically altered structures. The most striking result was that none of the eight tested compounds carrying methyl groups in both positions 5 and 8 of the aromatic ring exhibited functional binding. To understand the binding properties of these quinones on a molecular level, the structures of the reaction center-naphthoquinone complexes were predicted with ligand docking calculations. All protein,ligand structures show hydrogen bonds between the carbonyl oxygens of the quinone and AlaM260 and HisM219 as found for the native ubiquinone-10 in the X-ray structure. The center-to-center distance between the naphthoquinones at QA and the native ubiquinone-10 at QB (the secondary electron acceptor) is essentially the same, compared to the native structure. A detailed analysis of the docking calculations reveals that 5,8-disubstitution prohibits binding due to steric clashes of the 5-methyl group with the backbone atoms of AlaM260 and AlaM249. The experimentally determined binding free energies were reproduced with an rmsd of ,,4 kJ·mol,1 in most cases providing a valuable tool for the design of new artificial electron acceptors and inhibitors. [source] The active site of hydroxynitrile lyase from Prunus amygdalus: Modeling studies provide new insights into the mechanism of cyanogenesisPROTEIN SCIENCE, Issue 2 2002Ingrid Dreveny Abstract The FAD-dependent hydroxynitrile lyase from almond (Prunus amygdalus, PaHNL) catalyzes the cleavage of R -mandelonitrile into benzaldehyde and hydrocyanic acid. Catalysis of the reverse reaction,the enantiospecific formation of ,-hydroxynitriles,is now widely utilized in organic syntheses as one of the few industrially relevant examples of enzyme-mediated C,C bond formation. Starting from the recently determined X-ray crystal structure, systematic docking calculations with the natural substrate were used to locate the active site of the enzyme and to identify amino acid residues involved in substrate binding and catalysis. Analysis of the modeled substrate complexes supports an enzymatic mechanism that includes the flavin cofactor as a mere "spectator" of the reaction and relies on general acid/base catalysis by the conserved His-497. Stabilization of the negative charge of the cyanide ion is accomplished by a pronounced positive electrostatic potential at the binding site. PaHNL activity requires the FAD cofactor to be bound in its oxidized form, and calculations of the pKa of enzyme-bound HCN showed that the observed inactivation upon cofactor reduction is largely caused by the reversal of the electrostatic potential within the active site. The suggested mechanism closely resembles the one proposed for the FAD-independent, and structurally unrelated HNL from Hevea brasiliensis. Although the actual amino acid residues involved in the catalytic cycle are completely different in the two enzymes, a common motif for the mechanism of cyanogenesis (general acid/base catalysis plus electrostatic stabilization of the cyanide ion) becomes evident. [source] | ||||||||||