Two-stage method for protein-ligand docking. |
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Authors: | D Hoffmann B Kramer T Washio T Steinmetzer M Rarey T Lengauer |
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Affiliation: | German National Research Center for Information Technology, Institute for Algorithms and Scientific Computing (GMD-SCAI), Schloss Birlinghoven, D-53754 Sankt Augustin, Germany. Daniel.Hoffmann@GMD.DE |
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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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