title: Codon-level information improves predictions of inter-residue contacts in proteins by correlated mutation analysis.
abstract: Methods for analysing correlated mutations in proteins are becoming an increasingly powerful tool for predicting contacts within and between proteins. Nevertheless, limitations remain due to the requirement for large multiple sequence alignments (MSA) and the fact that, in general, only the relatively small number of top-ranking predictions are reliable. To date, methods for analysing correlated mutations have relied exclusively on amino acid MSAs as inputs. Here, we describe a new approach for analysing correlated mutations that is based on combined analysis of amino acid and codon MSAs. We show that a direct contact is more likely to be present when the correlation between the positions is strong at the amino acid level but weak at the codon level. The performance of different methods for analysing correlated mutations in predicting contacts is shown to be enhanced significantly when amino acid and codon data are combined.
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.|Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Etai
authors.initials: E
authors.lastname: Jacob
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel.
authors.forename: Ron
authors.initials: R
authors.lastname: Unger
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Amnon
authors.initials: A
authors.lastname: Horovitz
mesh_terms: D003062:Codon; D019295:Computational Biology / Q000379:methods*; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011485:Protein Binding; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D003062:Codon; D050505:Mutant Proteins; D011506:Proteins
keywords: biophysics; computational biology; correlated mutations; none; protein evolution; structural biology; structure prediction; systems biology