piperidines and inositol-1-phosphate

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.

Topics: Algorithms; Antithrombins; Dipeptides; Drug Design; Inositol Phosphates; Ligands; Models, Molecular; Molecular Structure; Phosphoric Monoester Hydrolases; Piperidines; Proteins; Thrombin