Dissecting protein architecture with communication blocks and communicating segment pairs

BMC Bioinformatics

Research

Elodie Laine¹  Alessandra Carbone²  Yasaman Karami³ 

[1] Sorbonne Universités, UPMC-Univ P6, CNRS, Laboratoire de Biologie Computationnelle et Quantitative - UMR 7238, 15 rue de l’Ecole de Médecine, 75006, Paris, France;Sorbonne Universités, UPMC-Univ P6, CNRS, Laboratoire de Biologie Computationnelle et Quantitative - UMR 7238, 15 rue de l’Ecole de Médecine, 75006, Paris, France;Institut Universitaire de France, 75005, Paris, France;Sorbonne Universités, UPMC-Univ P6, CNRS, Laboratoire de Biologie Computationnelle et Quantitative - UMR 7238, 15 rue de l’Ecole de Médecine, 75006, Paris, France;Sorbonne Universités, UPMC Univ Paris 06, ICS, 75005, Paris, France;

关键词: Protein structure;    Protein dynamics;    Allostery;    Molecular dynamics;    Residue network;   

DOI  :  10.1186/s12859-015-0855-y

来源: Springer

【 摘 要 】

BackgroundProteins adapt to environmental conditions by changing their shape and motions. Characterising protein conformational dynamics is increasingly recognised as necessary to understand how proteins function. Given a conformational ensemble, computational tools are needed to extract in a systematic way pertinent and comprehensive biological information.ResultsHere, we present a method, Communication Mapping (COMMA), to decipher the dynamical architecture of a protein. The method first extracts residue-based dynamic properties from all-atom molecular dynamics simulations. Then, it integrates them in a graph theoretic framework, where it identifies groups of residues or protein regions that mediate short- and long-range communication. COMMA introduces original concepts to contrast the different roles played by these regions, namely communication blocks and communicating segment pairs, and evaluates the connections and communication strengths between them. We show the utility and capabilities of COMMA by applying it to three archetypal proteins, namely protein A, the tyrosine kinase KIT and the tumour suppressor p53.ConclusionOur method permits to compare in a direct way the dynamical behaviour either of proteins with different characteristics or of the same protein in different conditions. It is useful to identify residues playing a key role in protein allosteric regulation and to explain the effects of deleterious mutations in a mechanistic way. COMMA is a fully automated tool with broad applicability. It is freely available to the community at www.lcqb.upmc.fr/COMMA.

【 授权许可】

Unknown   
© Karami et al. 2016. This article is published under license to BioMed Central Ltd. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.