title: Two-stage method for protein-ligand docking.
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.
authors.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
authors.forename: D
authors.initials: D
authors.lastname: Hoffmann
authors.forename: B
authors.initials: B
authors.lastname: Kramer
authors.forename: T
authors.initials: T
authors.lastname: Washio
authors.forename: T
authors.initials: T
authors.lastname: Steinmetzer
authors.forename: M
authors.initials: M
authors.lastname: Rarey
authors.forename: T
authors.initials: T
authors.lastname: Lengauer
mesh_terms: D000465:Algorithms; D000991:Antithrombins / Q000737:chemistry; D004151:Dipeptides / Q000737:chemistry; D015195:Drug Design; D007295:Inositol Phosphates / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry; D010880:Piperidines / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000737:chemistry
chemical_list: D000991:Antithrombins; D004151:Dipeptides; D007295:Inositol Phosphates; D008024:Ligands; D010880:Piperidines; D011506:Proteins; C002647:inositol 1-phosphate; C038708:N(alpha)-(2-naphthylsulfonylglycyl)-4-amidinophenylalanine piperidide; D010744:Phosphoric Monoester Hydrolases; C021822:myo-inositol-1 (or 4)-monophosphatase; D013917:Thrombin