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Two-stage method for protein-ligand docking.

D Hoffmann·B Kramer·T Washio·T Steinmetzer·M Rarey·T Lengauer
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Abstract

A two-stage method for the computational prediction of the structure of protein-ligand complexes is proposed. Given an experimentally determined structure of the protein, in the first stage a large number of plausible ligand conformations is generated using the fast docking algorithm FlexX. In the second stage these conformations are minimized and reranked using a method based on a classical force field. The two-stage method is tested for 10 different protein-ligand complexes. For 9 of them experimentally determined structures are known. It turns out that the two-stage method strongly improves the predictive power as compared to that of the fast docking stage alone. The tenth case is a bona fide prediction of a complex of thrombin with a new inhibitor for which no experimentally determined structure is available so far.

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AlgorithmsAntithrombinsDipeptidesDrug DesignInositol PhosphatesLigandsModels, MolecularMolecular StructurePhosphoric Monoester HydrolasesPiperidinesProteinsThrombinJournal ArticleResearch Support, Non-U.S. Gov't

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D Hoffmann, B Kramer, T Washio, T Steinmetzer, M Rarey, T Lengauer. 1999-10-21. Two-stage method for protein-ligand docking.. https://doi.org/10.1021/jm991090p

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