Direct coevolutionary couplings reflect biophysical residue interactions in proteins

The Journal of Chemical Physics
Alice CouckeMartin Weigt

Abstract

Coevolution of residues in contact imposes strong statistical constraints on the sequence variability between homologous proteins. Direct-Coupling Analysis (DCA), a global statistical inference method, successfully models this variability across homologous protein families to infer structural information about proteins. For each residue pair, DCA infers 21 × 21 matrices describing the coevolutionary coupling for each pair of amino acids (or gaps). To achieve the residue-residue contact prediction, these matrices are mapped onto simple scalar parameters; the full information they contain gets lost. Here, we perform a detailed spectral analysis of the coupling matrices resulting from 70 protein families, to show that they contain quantitative information about the physico-chemical properties of amino-acid interactions. Results for protein families are corroborated by the analysis of synthetic data from lattice-protein models, which emphasizes the critical effect of sampling quality and regularization on the biochemical features of the statistical coupling matrices.

References

Jan 20, 2018·Physical Review. E·Michael Schmidt, Kay Hamacher
Nov 10, 2017·Reports on Progress in Physics·S CoccoMartin Weigt
Aug 22, 2019·Proceedings of the National Academy of Sciences of the United States of America·John M NicoludisRachelle Gaudet
Jul 3, 2020·BMC Molecular and Cell Biology·Diego MarianoRaquel Cardoso de Melo-Minardi
Jun 13, 2018·Royal Society Open Science·Ricardo Nascimento Dos SantosFaruck Morcos

Citations

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Mar 17, 2011·Physical Review Letters·S Cocco, Rémi Monasson
May 20, 2011·Nucleic Acids Research·Robert D FinnSean R Eddy
Nov 23, 2011·Proceedings of the National Academy of Sciences of the United States of America·Faruck MorcosMartin Weigt
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Dec 18, 2015·Nucleic Acids Research·Robert D FinnAlex Bateman

Related Concepts

Amino Acids, I.V. solution additive
Gene Products, Protein
anthracene-1,5-dicarboxylic acid
Mass Spectrometry
Biophysics
Entropy
Structure
Biophysical Phenomena
Solvents
Analysis

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