Voprosy meditsinskoi khimii (ISSN 0042-8809)

Computer aided drug design based on structure of macromolecular target: I. search and description of ligandbinding site in target protein

   


1. Оrekhovich Institute of Biomedical Chemistry of RAMS
PubMed Id: 12243090
Year: 2002 vol: 48  issue:3  pages: 304-315
Abstract: Theapplicability ofmolecular docking method for finding of ligand binding site in target protein was tested.The basic principle of tested approach is the generation of hypotheses of protein-ligandcomplexes by molecular docking ofsmall ligand to all surface of protein. The subsequent scoring of these hypothesesutilizes the values of contact surfaces and complex formation energy. The dockingprocedure was executed using the original software DockSearch running on PC Pentium or SGIcomputers. A set of hypotheses of probable ligand positions on the protein surface wascreated and evaluated with the help of DockSearch. Energy minimization of molecularcomplexes was done using Sybyl 6.5 (Tripos Inc.) running on SGI server Origin200. Thefinal set of the best hypotheses of complexes was selected by the values of contactsurfaces and complex formation energy. The applicability and the limits of this approach were tested using known 3D structures of different proteins in free stateand in complexes with ligands. For most target proteins the method allows to find theligand binding site correctly. The accuracy of description of ligand binding site isadequate for subsequent searching of lead compounds by database mining. The reasons ofsome negative results obtained in testing of this approach are also discussed.
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Reference: Ivanov A.S., Dubanov A.V., Skvortsov V.S., Archakov A.I., Computer aided drug design based on structure of macromolecular target: I. search and description of ligandbinding site in target protein, Voprosy meditsinskoi khimii, 2002, vol: 48(3), 304-315.
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