title: Inferring functional information from domain co-evolution.
abstract: BACKGROUND
  Co-evolution is a powerful mechanism for understanding protein function. Prior work in this area has shown that co-evolving proteins are more likely to share the same function than those that do not because of functional constraints. Many of the efforts founded on this observation, however, are at the level of entire sequences, implicitly assuming that the complete protein sequence follows a single evolutionary trajectory. Since it is well known that a domain can exist in various contexts, this assumption is not valid for numerous multi-domain proteins. Motivated by these observations, we introduce a novel technique called Coevolutionary-Matrix that captures co-evolution between regions of two proteins. Instead of using existing domain information, the method exploits residue-level conservation to identify co-evolving regions that might correspond to domains.
  
  
  RESULTS
  We show that the Coevolutionary-Matrix method can detect greater number of known functional associations for the Escherichia coli proteins when compared with earlier implementations of phylogenetic profiles. Furthermore, co-evolving regions of proteins detected by our method enable us to make hypotheses about their specific functions, many of which are supported by existing biochemical studies.
authors.affiliation: Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Yohan
authors.initials: Y
authors.lastname: Kim
authors.forename: Mehmet
authors.initials: M
authors.lastname: Koyutürk
authors.forename: Umut
authors.initials: U
authors.lastname: Topkara
authors.forename: Ananth
authors.initials: A
authors.lastname: Grama
authors.forename: Shankar
authors.initials: S
authors.lastname: Subramaniam
mesh_terms: D000465:Algorithms; D001426:Bacterial Proteins / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D030562:Databases, Protein; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism; D019143:Evolution, Molecular; D016680:Genome, Bacterial; D008565:Membrane Proteins / Q000378:metabolism; D000072236:Methyl-Accepting Chemotaxis Proteins; D015233:Models, Statistical; D010802:Phylogeny; D011237:Predictive Value of Tests; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry; D016415:Sequence Alignment; D012984:Software
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D000072236:Methyl-Accepting Chemotaxis Proteins; D011506:Proteins; C489580:KdpD protein, E coli; D011494:Protein Kinases