title: Direct coupling analysis for protein contact prediction.
abstract: During evolution, structure, and function of proteins are remarkably conserved, whereas amino-acid sequences vary strongly between homologous proteins. Structural conservation constrains sequence variability and forces different residues to coevolve, i.e., to show correlated patterns of amino-acid occurrences. However, residue correlation may result from direct coupling, e.g., by a contact in the folded protein, or be induced indirectly via intermediate residues. To use empirically observed correlations for predicting residue-residue contacts, direct and indirect effects have to be disentangled. Here we present mechanistic details on how to achieve this using a methodology called Direct Coupling Analysis (DCA). DCA has been shown to produce highly accurate estimates of amino-acid pairs that have direct reciprocal constraints in evolution. Specifically, we provide instructions and protocols on how to use the algorithmic implementations of DCA starting from data extraction to predicted-contact visualization in contact maps or representative protein structures.
authors.affiliation: Center for Theoretical Biological Physics, Rice University, Houston, TX, USA.
authors.forename: Faruck
authors.initials: F
authors.lastname: Morcos
authors.forename: Terence
authors.initials: T
authors.lastname: Hwa
authors.forename: José N
authors.initials: JN
authors.lastname: Onuchic
authors.forename: Martin
authors.initials: M
authors.lastname: Weigt
mesh_terms: D000465:Algorithms; D000596:Amino Acids; D001665:Binding Sites; D008958:Models, Molecular; D054730:Protein Interaction Domains and Motifs; D011506:Proteins / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D011506:Proteins