MOTIVATION: A number of proteins of known three-dimensional (3D) structure exist, with yet unknown function. In light of the recent progress in structure determination methodology, this number is likely to increase rapidly. A novel method is presented here: 'Rate4Site', which maps the rate of evolution among homologous proteins onto the molecular surface of one of the homologues whose 3D-structure is known. Functionally important regions often correspond to surface patches of slowly evolving residues. RESULTS: Rate4Site estimates the rate of evolution of amino acid sites using the maximum likelihood (ML) principle. The ML estimate of the rates considers the topology and branch lengths of the phylogenetic tree, as well as the underlying stochastic process. To demonstrate its potency, we study the Src SH2 domain. Like previously established methods, Rate4Site detected the SH2 peptide-binding groove. Interestingly, it also detected inter-domain interactions between the SH2 domain and the rest of the Src protein that other methods failed to detect.
MOTIVATION: A number of proteins of known three-dimensional (3D) structure exist, with yet unknown function. In light of the recent progress in structure determination methodology, this number is likely to increase rapidly. A novel method is presented here: 'Rate4Site', which maps the rate of evolution among homologous proteins onto the molecular surface of one of the homologues whose 3D-structure is known. Functionally important regions often correspond to surface patches of slowly evolving residues. RESULTS: Rate4Site estimates the rate of evolution of amino acid sites using the maximum likelihood (ML) principle. The ML estimate of the rates considers the topology and branch lengths of the phylogenetic tree, as well as the underlying stochastic process. To demonstrate its potency, we study the Src SH2 domain. Like previously established methods, Rate4Site detected the SH2 peptide-binding groove. Interestingly, it also detected inter-domain interactions between the SH2 domain and the rest of the Src protein that other methods failed to detect.
Authors: Debanu Das; Piotr Kozbial; Herbert L Axelrod; Mitchell D Miller; Daniel McMullan; S Sri Krishna; Polat Abdubek; Claire Acosta; Tamara Astakhova; Prasad Burra; Dennis Carlton; Connie Chen; Hsiu-Ju Chiu; Thomas Clayton; Marc C Deller; Lian Duan; Ylva Elias; Marc-André Elsliger; Dustin Ernst; Carol Farr; Julie Feuerhelm; Anna Grzechnik; Slawomir K Grzechnik; Joanna Hale; Gye Won Han; Lukasz Jaroszewski; Kevin K Jin; Hope A Johnson; Heath E Klock; Mark W Knuth; Abhinav Kumar; David Marciano; Andrew T Morse; Kevin D Murphy; Edward Nigoghossian; Amanda Nopakun; Linda Okach; Silvya Oommachen; Jessica Paulsen; Christina Puckett; Ron Reyes; Christopher L Rife; Natasha Sefcovic; Sebastian Sudek; Henry Tien; Christine Trame; Christina V Trout; Henry van den Bedem; Dana Weekes; Aprilfawn White; Qingping Xu; Keith O Hodgson; John Wooley; Ashley M Deacon; Adam Godzik; Scott A Lesley; Ian A Wilson Journal: Proteins Date: 2009-05-01