Direct-coupling analysis of residue coevolution captures native contacts across many protein families Faruck Morcos, Andrea Pagnani, Bryan Lunt, Arianna Bertolino, Debora S. Marks, Chris Sander, Riccardo Zecchina, José N. Onuchic, Terence Hwa, and Martin Weigt PNAS December 6, 2011 108 (49) E1293-E1301; https://doi.org/10.1073/pnas.1111471108 Semantic Scholar is a free, AI-powered research tool for scientific literature, based at the Allen Institute for AI. Direct coupling analysis for protein contact prediction. The basic hypothesis connecting correlated substitution pat- terns and residue–residue contacts is very simple: If two residues of a protein or a pair of interacting proteins form a contact, a destabilizing amino acid substitution at one position is expected tobecompensatedbyasubstitutionoftheotherpositionoverthe evolutionary timescale, in order for the residue pair to maintain attractive interaction. DCA is shown to yield a large number of correctly predicted contacts, recapitulating the global structure of the contact map for the majority of the protein domains examined. Can three-dimensional contacts in protein structures be predicted by analysis of correlated mutations? You are currently offline. Quantitative Biology - Quantitative Methods; Condensed Matter - Statistical Mechanics. Direct-coupling analysis of residue coevolution captures native contacts across many protein families. It has long been suggested that the resulting correlations among amino acid compositions at different sequence positions can be exploited to infer spatial contacts within the … It has long been suggested that the resulting correlations among amino acid compositions at different sequence positions can be exploited to infer spatial contacts within the tertiary protein structure. Crucial to this inference is the ability to disentangle direct and indirect correlations, as accomplished by the recently introduced direct-coupling analysis (DCA). Direct-coupling analysis of residue coevolution captures native contacts across many protein families. Use, Smithsonian Direct-coupling analysis of residue coevolution captures native contacts across many protein families The similarity in the three-dimensional structures of homologous proteins imposes strong constraints on their sequence variability. Furthermore, our analysis captures clear signals beyond intradomain residue contacts, arising, e.g., from alternative protein conformations, ligand-mediated residue couplings, and interdomain interactions in protein oligomers. The similarity in the three-dimensional structures of homologous proteins imposes strong constraints on their sequence variability. Some features of the site may not work correctly. Large-scale identification of coevolution signals across homo-oligomeric protein interfaces by direct coupling analysis, Statistical investigations of protein residue direct couplings, Evolutionary couplings detect side-chain interactions, From residue coevolution to protein conformational ensembles and functional dynamics, Patterns of coevolving amino acids unveil structural and dynamical domains. 3D Protein Structure Predicted from Sequence, Mutual information without the influence of phylogeny or entropy dramatically improves residue contact prediction, Using multiple interdependency to separate functional from phylogenetic correlations in protein alignments, Blog posts, news articles and tweet counts and IDs sourced by, Proceedings of the National Academy of Sciences, View 5 excerpts, cites background and methods, Protein science : a publication of the Protein Society, By clicking accept or continuing to use the site, you agree to the terms outlined in our, A Fundamental Breakthrough in Protein Folding. Crucial to this inference is the ability to disentangle direct and indirect correlations, as accomplished by the recently introduced direct-coupling analysis (DCA….