title: Role of binding entropy in the refinement of protein-ligand docking predictions: analysis based on the use of 11 scoring functions.
abstract: We present results of testing the ability of eleven popular scoring functions to predict native docked positions using a recently developed method (Ruvinsky and Kozintsev, J Comput Chem 2005, 26, 1089) for estimation the entropy contributions of relative motions to protein-ligand binding affinity. The method is based on the integration of the configurational integral over clusters obtained from multiple docked positions. We use a test set of 100 PDB protein-ligand complexes and ensembles of 101 docked positions generated by (Wang et al. J Med Chem 2003, 46, 2287) for each ligand in the test set. To test the suggested method we compared the averaged root-mean square deviations (RMSD) of the top-scored ligand docked positions, accounting and not accounting for entropy contributions, relative to the experimentally determined positions. We demonstrate that the method increases docking accuracy by 10-21% when used in conjunction with the AutoDock scoring function, by 2-25% with G-Score, by 7-41% with D-Score, by 0-8% with LigScore, by 1-6% with PLP, by 0-12% with LUDI, by 2-8% with F-Score, by 7-29% with ChemScore, by 0-9% with X-Score, by 2-19% with PMF, and by 1-7% with DrugScore. We also compared the performance of the suggested method with the method based on ranking by cluster occupancy only. We analyze how the choice of a clustering-RMSD and a low bound of dense clusters impacts on docking accuracy of the scoring methods. We derive optimal intervals of the clustering-RMSD for 11 scoring functions.
authors.affiliation: Center for Bioinformatics, The University of Kansas, 2030 Becker Drive, Lawrence, Kansas 66047, USA. ruvinsky@ku.edu
authors.forename: Anatoly M
authors.initials: AM
authors.lastname: Ruvinsky
mesh_terms: D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D019277:Entropy; D008024:Ligands; D004364:Pharmaceutical Preparations; D011485:Protein Binding; D011506:Proteins / Q000032:analysis* / Q000378:metabolism*
chemical_list: D008024:Ligands; D004364:Pharmaceutical Preparations; D011506:Proteins