Abstract
Molecular recognition plays a fundamental role in all biological processes, and that is why great efforts have been made to understand and predict protein–ligand interactions. Finding a molecule that can potentially bind to a target protein is particularly essential in drug discovery and still remains an expensive and time‐consuming task. In silico, tools are frequently used to screen molecular libraries to identify new lead compounds, and if protein structure is known, various protein–ligand docking programs can be used. The aim of docking procedure is to predict correct poses of ligand in the binding site of the protein as well as to score them according to the strength of interaction in a reasonable time frame. The purpose of our studies was to present the novel consensus approach to predict both protein–ligand complex structure and its corresponding binding affinity. Our method used as the input the results from seven docking programs (Surflex, LigandFit, Glide, GOLD, FlexX, eHiTS, and AutoDock) that are widely used for docking of ligands. We evaluated it on the extensive benchmark dataset of 1300 protein–ligands pairs from refined PDBbind database for which the structural and affinity data was available. We compared independently its ability of proper scoring and posing to the previously proposed methods. In most cases, our method is able to dock properly approximately 20% of pairs more than docking methods on average, and over 10% of pairs more than the best single program. The RMSD value of the predicted complex conformation versus its native one is reduced by a factor of 0.5 Å. Finally, we were able to increase the Pearson correlation of the predicted binding affinity in comparison with the experimental value up to 0.5. © 2010 Wiley Periodicals, Inc. J Comput Chem 32: 568–581, 2011