Direct coevolutionary couplings reflect biophysical residue interactions in proteins

The Journal of Chemical Physics
Alice CouckeMartin Weigt


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.


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


Mar 1, 1997·Protein Science : a Publication of the Protein Society·J SkolnickA Godzik
Jan 27, 1999·Bioinformatics·Sean R Eddy
Dec 11, 1999·Nucleic Acids Research·H M BermanP E Bourne
Nov 1, 2006·Protein Science : a Publication of the Protein Society·Min-Yi Shen, Andrej Sali
Jan 1, 2009·Proceedings of the National Academy of Sciences of the United States of America·Martin WeigtTerence Hwa
Jan 27, 2011·Proteins·Sivaraman BalakrishnanChristopher James Langmead
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
Feb 16, 2013·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·Magnus EkebergErik Aurell
Sep 7, 2013·Proceedings of the National Academy of Sciences of the United States of America·Hetunandan KamisettyDavid Baker
Aug 15, 2014·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·J P BartonRémi Monasson
Oct 10, 2014·PLoS Computational Biology·Christoph FeinauerErik Aurell
Oct 29, 2014·Nucleic Acids Research·UniProt Consortium
Oct 22, 2015·Proceedings of the National Academy of Sciences of the United States of America·Ludovico SuttoFrancesco Luigi Gervasio
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
Biophysical Phenomena

Trending Feeds


Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Sexual Dimorphism in Neurodegeneration

There exist sex differences in neurodevelopmental and neurodegenerative disorders. For instance, multiple sclerosis is more common in women, whereas Parkinson’s disease is more common in men. Here is the latest research on sexual dimorphism in neurodegeneration

HLA Genetic Variation

HLA genetic variation has been found to confer risk for a wide variety of diseases. Identifying these associations and understanding their molecular mechanisms is ongoing and holds promise for the development of therapeutics. Find the latest research on HLA genetic variation here.

Super-resolution Microscopy

Super-resolution microscopy is the term commonly given to fluorescence microscopy techniques with resolutions that are not limited by the diffraction of light. Here are the latest discoveries pertaining to super-resolution microscopy.

Genetic Screens in iPSC-derived Brain Cells

Genetic screening is a critical tool that can be employed to define and understand gene function and interaction. This feed focuses on genetic screens conducted using induced pluripotent stem cell (iPSC)-derived brain cells.

Brain Lower Grade Glioma

Low grade gliomas in the brain form from oligodendrocytes and astrocytes and are the slowest-growing glioma in adults. Discover the latest research on these brain tumors here.

CD4/CD8 Signaling

Cluster of differentiation 4 and 8 (CD8 and CD8) are glycoproteins founds on the surface of immune cells. Here is the latest research on their role in cell signaling pathways.

Alignment-free Sequence Analysis Tools

Alignment-free sequence analyses have been applied to problems ranging from whole-genome phylogeny to the classification of protein families, identification of horizontally transferred genes, and detection of recombined sequences. Here is the latest research.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Faruck MorcosMartin Weigt
Methods in Molecular Biology
Faruck MorcosMartin Weigt
Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics
Magnus EkebergErik Aurell
Proceedings of the National Academy of Sciences of the United States of America
Thomas GueudréAndrea Pagnani
© 2020 Meta ULC. All rights reserved