title: Determinants of protein function revealed by combinatorial entropy optimization.
abstract: We use a new algorithm (combinatorial entropy optimization [CEO]) to identify specificity residues and functional subfamilies in sets of proteins related by evolution. Specificity residues are conserved within a subfamily but differ between subfamilies, and they typically encode functional diversity. We obtain good agreement between predicted specificity residues and experimentally known functional residues in protein interfaces. Such predicted functional determinants are useful for interpreting the functional consequences of mutations in natural evolution and disease.
authors.affiliation: Computational Biology Center, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. borisr@mskcc.org
authors.forename: Boris
authors.initials: B
authors.lastname: Reva
authors.forename: Yevgeniy
authors.initials: Y
authors.lastname: Antipin
authors.forename: Chris
authors.initials: C
authors.lastname: Sander
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D020650:Combinatorial Chemistry Techniques; D019277:Entropy; D019143:Evolution, Molecular; D020558:GTP Phosphohydrolases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
chemical_list: D018797:Cell Cycle Proteins; D020558:GTP Phosphohydrolases