Protein ligand docking based on empirical method for binding affinity estimation

An empirical protein-ligand binding affinity estimation method, SCORE, was incorporated into a popular docking program, DOCK4. The combined program, S coreDock, was used to reconstruct the 200 protein-ligand complex structures and found to give good results for the complexes with high binding affinit ies. A quality assessment method for docking results from ScoreDock was dev eloped based on the whole test set and tested by additionally selected comp lexes. The method significantly improves the docking accuracy and was shown to be reliable in docking quality assessment. As a docking tool in structu ral based drug design, ScoreDock can screen out final hits directly based o n the predicted negative logarithms of dissociation equilibrium constants o f protein-ligand complexes, and can explicitly deal with structure water mo lecules, as well as metal atoms.