Evaluation of the Searching Abilities of HBOP and HBSITE for Binding Pocket Detection

We evaluated the pocket-searching abilities of the computer programs HBOP and HBSITE, in which hydrophobic potentials calculated on grid points generated around a protein function as an indicator of the pocket-like property-using a test set of 458 experimentally observed structures of protein-ligand complexes. The results were compared with those obtained using the alternative algorithms PASS and SiteID, which only consider geometric properties, and Q-SiteFinder, which considers not only geometry but also physicochemical properties. The comparison revealed that HBOP and HBSITE could detect experimentally observed ligand-binding pockets for more test complexes than PASS and SiteID. In addition, the success rate of HBOP for detecting binding pockets was higher than that of Q-SiteFinder, and that of HBSITE was comparable with that of Q-SiteFinder. Results of tests for ligand-unbound state proteins indicated that HBSITE was more appropriate than Q-SiteFinder for pocket searches of ligand-unbound proteins, and HBSITE was more robust than Q-SiteFinder against structural differences between ligand-bound and -unbound state proteins. (C) 2009 Wiley Periodicals, Inc. J Comput Chem 30: 2728-2737, 2009