title: Surface-based protein binding pocket similarity.
abstract: Protein similarity comparisons may be made on a local or global basis and may consider sequence information or differing levels of structural information. We present a local three-dimensional method that compares protein binding site surfaces in full atomic detail. The approach is based on the morphological similarity method which has been widely applied for global comparison of small molecules. We apply the method to all-by-all comparisons two sets of human protein kinases, a very diverse set of ATP-bound proteins from multiple species, and three heterogeneous benchmark protein binding site data sets. Cases of disagreement between sequence-based similarity and binding site similarity yield informative examples. Where sequence similarity is very low, high pocket similarity can reliably identify important binding motifs. Where sequence similarity is very high, significant differences in pocket similarity are related to ligand binding specificity and similarity. Local protein binding pocket similarity provides qualitatively complementary information to other approaches, and it can yield quantitative information in support of functional annotation.
authors.affiliation: Department of Bioengineering and Therapeutic Sciences, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California 94158-9001, USA.
authors.forename: Russell
authors.initials: R
authors.lastname: Spitzer
authors.forename: Ann E
authors.initials: AE
authors.lastname: Cleves
authors.forename: Ajay N
authors.initials: AN
authors.lastname: Jain
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D006801:Humans; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D011494:Protein Kinases