title: Normal Modes Expose Active Sites in Enzymes.
abstract: Accurate prediction of active sites is an important tool in bioinformatics. Here we present an improved structure based technique to expose active sites that is based on large changes of solvent accessibility accompanying normal mode dynamics. The technique which detects EXPOsure of active SITes through normal modEs is named EXPOSITE. The technique is trained using a small 133 enzyme dataset and tested using a large 845 enzyme dataset, both with known active site residues. EXPOSITE is also tested in a benchmark protein ligand dataset (PLD) comprising 48 proteins with and without bound ligands. EXPOSITE is shown to successfully locate the active site in most instances, and is found to be more accurate than other structure-based techniques. Interestingly, in several instances, the active site does not correspond to the largest pocket. EXPOSITE is advantageous due to its high precision and paves the way for structure based prediction of active site in enzymes.
authors.affiliation: Faculty of Medicine in the Galilee, Bar Ilan University, Safed, Israel.
authors.forename: Yitav
authors.initials: Y
authors.lastname: Glantz-Gashai
authors.affiliation: Faculty of Medicine in the Galilee, Bar Ilan University, Safed, Israel.
authors.forename: Tomer
authors.identifier: 0000-0002-5011-5477
authors.initials: T
authors.lastname: Meirson
authors.affiliation: Faculty of Medicine in the Galilee, Bar Ilan University, Safed, Israel.
authors.forename: Abraham O
authors.initials: AO
authors.lastname: Samson
mesh_terms: D020134:Catalytic Domain; D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D004798:Enzymes / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure*; D008958:Models, Molecular; D012997:Solvents
chemical_list: D004798:Enzymes; D012997:Solvents