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

   
Ivanov A.S.1, Dubanov A.V.1, Skvortsov V.S.1, Archakov A.I.1

1. Orekhovich Institute of Biomedical Chemistry of RAMS
PubMed Id: 12243090
Year: 2002  Volume: 48  Issue: 3  Pages: 304-315
The applicability of molecular docking method for finding of ligand binding site in a target protein was tested. The basic principle of tested approach consists in generation of hypotheses of protein-ligand complexes by molecular docking of small ligand to all surface of protein. The subsequent scoring of these hypotheses utilizes the values of contact surfaces and complex formation energy. The docking procedure was executed using the original software DockSearch running on PC Pentium or SGI computers. A set of hypotheses of probable ligand positions on the protein surface was created and evaluated with the help of DockSearch. Energy minimization of molecular complexes was done using Sybyl 6.5 (Tripos Inc.) running on SGI server Origin 200. The final set of the best hypotheses of complexes were selected by the values of contact surfaces and complex formation energy. The applicability and the limits of this approach was tested using known 3D structures of different proteins in free state and in complexes with ligands. For most target proteins the method allows to find the ligand binding site correctly. The accuracy of description of ligand binding site is adequate for subsequent searching of lead compounds by database mining. The reasons of some negative results obtained in testing of this approach are also discussed.
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Ivanov, A. S., Dubanov, A. V., Skvortsov, V. S., Archakov, A. I. (2002). Computer aided drug design based on structure of macromolecular target: I. search and description of ligandbinding site in target protein. Voprosy meditsinskoi khimii, 48(3), 304-315.
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