Direct coupling analysis for protein contact prediction

Methods in Molecular Biology
Faruck MorcosMartin Weigt

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.

References

Jul 3, 2015·BMC Bioinformatics·Rocío EspadaDiego U Ferreiro
Dec 22, 2016·PLoS Computational Biology·Andrew F Neuwald, Stephen F Altschul
Jul 26, 2017·Nature Structural & Molecular Biology·Tom LopezJudith Frydman
Sep 5, 2015·Scientific Reports·Ricardo N Dos SantosJosé N Onuchic
Aug 16, 2019·PLoS Computational Biology·Jacopo MarchiThierry Mora
Jul 19, 2018·Bioinformatics·Ruben Sanchez-GarciaJoan Segura
Oct 7, 2019·Proteins·Rojan ShresthaAndras Fiser
Jan 17, 2020·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Francesca NerattiniIvan Coluzza
May 31, 2018·Microbial Genomics·Santeri PuranenJukka Corander
Oct 17, 2019·BMC Bioinformatics·Yiren JianChen Zeng
Jun 13, 2018·Royal Society Open Science·Ricardo Nascimento Dos SantosFaruck Morcos

Related Concepts

Protein Interaction Domains and Motifs
Homologous Gene

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