Bioinformatics Vol. 18 no. 90001 2002
Pages S71-S77
© 2002 Oxford University Press
Rate4Site: an algorithmic tool for the identification of functional regions in proteins by surface mapping of evolutionary determinants within their homologues
1 The Institute of Statistical Mathematics, 4-6-7 Minami-Azabu,
Minato-ku, Tokyo 106-8569, Japan
2 Department of Biochemistry, George S. Wise Faculty of Life Sciences,
Tel Aviv University, Ramat Aviv 69978, Israel
Received on January 24, 2002
; revised on April 1, 2002
; accepted on April 1, 2002
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.
Availability: Rate4Site can be downloaded at: http://ashtoret.tau.ac.il/ It is implemented as a web server at: bioinfo.tau.ac.il/ConSurf
Contact: tal{at}ism.ac.jp rebell{at}ashtoret.tau.ac.il fabian{at}ashtoret.tau.ac.il bental{at}ashtoret.tau.ac.il
Supplementary Information: Multiple sequence alignment of homologous SH2 domains, the corresponding phylogenetic tree and additional examples are available at http://ashtoret.tau.ac.il/~rebell
Keywords: rate variation among sites; evolutionary conservation; protein evolution; maximum likelihood; SH2 domains.
* To whom correspondence should be addressed.
These authors contributed equally.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Garcia-Boronat, C. M. Diez-Rivero, E. L. Reinherz, and P. A. Reche PVS: a web server for protein sequence variability analysis tuned to facilitate conserved epitope discovery Nucleic Acids Res., April 27, 2008; (2008) gkn211v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Ye, G. Vriend, and A. P. IJzerman Tracing evolutionary pressure Bioinformatics, April 1, 2008; 24(7): 908 - 915. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Guney, N. Tuncbag, O. Keskin, and A. Gursoy HotSprint: database of computational hot spots in protein interfaces Nucleic Acids Res., January 11, 2008; 36(suppl_1): D662 - D666. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Brilli, R. Fani, and P. Lio Current trends in the bioinformatic sequence analysis of metabolic pathways in prokaryotes Brief Bioinform, January 1, 2008; 9(1): 34 - 45. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Boter, B. Amigues, J. Peart, C. Breuer, Y. Kadota, C. Casais, G. Moore, C. Kleanthous, F. Ochsenbein, K. Shirasu, et al. Structural and Functional Analysis of SGT1 Reveals That Its Interaction with HSP90 Is Required for the Accumulation of Rx, an R Protein Involved in Plant Immunity PLANT CELL, November 1, 2007; 19(11): 3791 - 3804. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Stern, A. Doron-Faigenboim, E. Erez, E. Martz, E. Bacharach, and T. Pupko Selecton 2007: advanced models for detecting positive and purifying selection using a Bayesian inference approach Nucleic Acids Res., July 13, 2007; 35(suppl_2): W506 - W511. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. T. Ranjith-Kumar, W. Miller, J. Sun, J. Xiong, J. Santos, I. Yarbrough, R. J. Lamb, J. Mills, K. E. Duffy, S. Hoose, et al. Effects of Single Nucleotide Polymorphisms on Toll-like Receptor 3 Activity and Expression in Cultured Cells J. Biol. Chem., June 15, 2007; 282(24): 17696 - 17705. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Thilakaraj, K. Raghunathan, S. Anishetty, and G. Pennathur In silico identification of putative metal binding motifs Bioinformatics, February 1, 2007; 23(3): 267 - 271. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Doron-Faigenboim and T. Pupko A Combined Empirical and Mechanistic Codon Model Mol. Biol. Evol., February 1, 2007; 24(2): 388 - 397. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Mayrose, T. Shlomi, N. D. Rubinstein, J. M. Gershoni, E. Ruppin, R. Sharan, and T. Pupko Epitope mapping using combinatorial phage-display libraries: a graph-based algorithm Nucleic Acids Res., January 12, 2007; 35(1): 69 - 78. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Chakrabarti and C. J. Lanczycki Analysis and prediction of functionally important sites in proteins Protein Sci., January 1, 2007; 16(1): 4 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Liang, C. Zhang, S. Liu, and Y. Zhou Protein binding site prediction using an empirical scoring function Nucleic Acids Res., August 7, 2006; 34(13): 3698 - 3707. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Carro, M. Tress, D. de Juan, F. Pazos, P. Lopez-Romero, A. del Sol, A. Valencia, and A. M. Rojas TreeDet: a web server to explore sequence space. Nucleic Acids Res., July 1, 2006; 34(Web Server issue): W110 - W115. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Becker, V. Meyer, H. Madaoui, and R. Guerois Detection of a tandem BRCT in Nbs1 and Xrs2 with functional implications in the DNA damage response Bioinformatics, June 1, 2006; 22(11): 1289 - 1292. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Stern and T. Pupko An Evolutionary Space-Time Model with Varying Among-Site Dependencies Mol. Biol. Evol., February 1, 2006; 23(2): 392 - 400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Pei, W. Cai, L. N. Kinch, and N. V. Grishin Prediction of functional specificity determinants from protein sequences using log-likelihood ratios Bioinformatics, January 15, 2006; 22(2): 164 - 171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Gabant, S. Auxilien, I. Tuszynska, M. Locard, M. J. Gajda, G. Chaussinand, B. Fernandez, A. Dedieu, H. Grosjean, B. Golinelli-Pimpaneau, et al. THUMP from archaeal tRNA:m22G10 methyltransferase, a genuine autonomously folding domain. Nucleic Acids Res., January 1, 2006; 34(9): 2483 - 2494. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Kim and Y. Kliger Discovering hidden viral piracy Bioinformatics, December 1, 2005; 21(23): 4216 - 4222. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Landau, I. Mayrose, Y. Rosenberg, F. Glaser, E. Martz, T. Pupko, and N. Ben-Tal ConSurf 2005: the projection of evolutionary conservation scores of residues on protein structures Nucleic Acids Res., July 1, 2005; 33(suppl_2): W299 - W302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Magyar, M. M. Gromiha, G. Pujadas, G. E. Tusnady, and I. Simon SRide: a server for identifying stabilizing residues in proteins Nucleic Acids Res., July 1, 2005; 33(suppl_2): W303 - W305. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Buck and W. R. Atchley Networks of Coevolving Sites in Structural and Functional Domains of Serpin Proteins Mol. Biol. Evol., July 1, 2005; 22(7): 1627 - 1634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Bordner and R. Abagyan REVCOM: a robust Bayesian method for evolutionary rate estimation Bioinformatics, May 15, 2005; 21(10): 2315 - 2321. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Mousson, A. Lautrette, J.-Y. Thuret, M. Agez, R. Courbeyrette, B. Amigues, E. Becker, J.-M. Neumann, R. Guerois, C. Mann, et al. Structural basis for the interaction of Asf1 with histone H3 and its functional implications PNAS, April 26, 2005; 102(17): 5975 - 5980. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Blouin, D. Butt, and A. J. Roger Impact of Taxon Sampling on the Estimation of Rates of Evolution at Sites Mol. Biol. Evol., March 1, 2005; 22(3): 784 - 791. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Guo, Y. Shi, and Z. Sun A novel statistical ligand-binding site predictor: application to ATP-binding sites Protein Eng. Des. Sel., February 1, 2005; 18(2): 65 - 70. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Neshich, A. L. Mancini, M. E. B. Yamagishi, P. R. Kuser, R. Fileto, I. P. Pinto, J. F. Palandrani, J. N. Krauchenco, C. Baudet, A. J. Montagner, et al. STING Report: convenient web-based application for graphic and tabular presentations of protein sequence, structure and function descriptors from the STING database Nucleic Acids Res., January 1, 2005; 33(suppl_1): D269 - D274. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Fleishman, S. Harrington, R. A. Friesner, B. Honig, and N. Ben-Tal An Automatic Method for Predicting Transmembrane Protein Structures Using Cryo-EM and Evolutionary Data Biophys. J., November 1, 2004; 87(5): 3448 - 3459. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Melamed, M. Mark-Danieli, M. Kenan-Eichler, O. Kraus, A. Castiel, N. Laham, T. Pupko, F. Glaser, N. Ben-Tal, and E. Bacharach The Conserved Carboxy Terminus of the Capsid Domain of Human Immunodeficiency Virus Type 1 Gag Protein Is Important for Virion Assembly and Release J. Virol., September 15, 2004; 78(18): 9675 - 9688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Mayrose, D. Graur, N. Ben-Tal, and T. Pupko Comparison of Site-Specific Rate-Inference Methods for Protein Sequences: Empirical Bayesian Methods Are Superior Mol. Biol. Evol., September 1, 2004; 21(9): 1781 - 1791. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Neshich, W. Rocchia, A. L. Mancini, M. E. B. Yamagishi, P. R. Kuser, R. Fileto, C. Baudet, I. P. Pinto, A. J. Montagner, J. F. Palandrani, et al. JavaProtein Dossier: a novel web-based data visualization tool for comprehensive analysis of protein structure Nucleic Acids Res., July 1, 2004; 32(suppl_2): W595 - W601. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Blouin, D. Butt, and A. J. Roger Rapid evolution in conformational space: A study of loop regions in a ubiquitous GTP binding domain Protein Sci., March 1, 2004; 13(3): 608 - 616. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Opatowsky, O. Chomsky-Hecht, M.-G. Kang, K. P. Campbell, and J. A. Hirsch The Voltage-dependent Calcium Channel {beta} Subunit Contains Two Stable Interacting Domains J. Biol. Chem., December 26, 2003; 278(52): 52323 - 52332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Weiss, I. Gottfried, I. Mayrose, S. L. Khare, M. Xiang, S. J. Dawson, and K. B. Avraham The DFNA15 Deafness Mutation Affects POU4F3 Protein Stability, Localization, and Transcriptional Activity Mol. Cell. Biol., November 15, 2003; 23(22): 7957 - 7964. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Bradford and D. R. Westhead Asymmetric mutation rates at enzyme-inhibitor interfaces: Implications for the protein-protein docking problem Protein Sci., September 1, 2003; 12(9): 2099 - 2103. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M RamShankar, S Girirajan, O Dagan, H M Ravi Shankar, R Jalvi, R Rangasayee, K B Avraham, and A Anand Contribution of connexin26 (GJB2) mutations and founder effect to non-syndromic hearing loss in India J. Med. Genet., May 1, 2003; 40(5): e68 - 68. [Full Text] [PDF]
|
|
|
|
|
|
C. Blouin, Y. Boucher, and A. J. Roger Inferring functional constraints and divergence in protein families using 3D mapping of phylogenetic information Nucleic Acids Res., January 15, 2003; 31(2): 790 - 797. [Abstract] [Full Text] [PDF]
|
|