title: Rapid comparison of protein binding site surfaces with property encoded shape distributions.
abstract: Patterns in shape and property distributions on the surface of binding sites are often conserved across functional proteins without significant conservation of the underlying amino-acid residues. To explore similarities of these sites from the viewpoint of a ligand, a sequence and fold-independent method was created to rapidly and accurately compare binding sites of proteins represented by property-mapped triangulated Gauss-Connolly surfaces. Within this paradigm, signatures for each binding site surface are produced by calculating their property-encoded shape distributions (PESD), a measure of the probability that a particular property will be at a specific distance to another on the molecular surface. Similarity between the signatures can then be treated as a measure of similarity between binding sites. As postulated, the PESD method rapidly detected high levels of similarity in binding site surface characteristics even in cases where there was very low similarity at the sequence level. In a screening experiment involving each member of the PDBBind 2005 data set as a query against the rest of the set, PESD was able to retrieve a binding site with identical E.C. (Enzyme Commission) numbers as the top match in 79.5% of cases. The ability of the method in detecting similarity in binding sites with low sequence conservations was compared to state-of-the-art binding site comparison methods.
authors.affiliation: Department of Chemistry and Chemical Biology, and RECCR Center, Rensselaer Polytechnic Institute, 110 Eighth Street, Troy, New York 12180.
authors.forename: Sourav
authors.initials: S
authors.lastname: Das
authors.forename: Arshad
authors.initials: A
authors.lastname: Kokardekar
authors.forename: Curt M
authors.initials: CM
authors.lastname: Breneman
mesh_terms: D001665:Binding Sites; D003201:Computers; D018698:Glutamic Acid / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D013997:Time Factors; D014584:User-Computer Interface
chemical_list: D007295:Inositol Phosphates; D008024:Ligands; D011506:Proteins; D018698:Glutamic Acid