Residues Coevolution Guides the Systematic Identification of Alternative Functional Conformations in Proteins

被引：41

作者：

Sfriso, Pedro ^{[1
,2
]}

Duran-Frigola, Miquel ^{[1
,2
]}

Mosca, Roberto ^{[1
,2
]}

Emperador, Agusti ^{[1
,2
]}

Aloy, Patrick ^{[1
,2
,3
]}

Orozco, Modesto ^{[1
,2
,4
]}

机构：

[1] IRB Barcelona, Inst Res Biomed, C Baldiri Reixac 10, Barcelona 08028, Spain

[2] Joint BSC IRB Res Program Computat Biol, C Baldiri Reixac 10, Barcelona 08028, Spain

[3] ICREA, Pg Lluis Companys 23, Barcelona 08011, Spain

[4] Univ Barcelona, Dept Biochem & Mol Biol, Av Diagonal 647, E-08028 Barcelona, Spain

来源：

STRUCTURE | 2016年 / 24卷 / 01期

基金：

欧洲研究理事会;

关键词：

DISCRETE MOLECULAR-DYNAMICS; TRANSITION PATHWAYS; SIMULATION; EFFICIENT; REPRESENTATION; PREDICTION; CONTACTS; SEQUENCE; MOTIONS; MODELS;

D O I：

10.1016/j.str.2015.10.025

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We present here a new approach for the systematic identification of functionally relevant conformations in proteins. Our fully automated pipeline, based on discrete molecular dynamics enriched with coevolutionary information, is able to capture alternative conformational states in 76% of the proteins studied, providing key atomic details for understanding their function and mechanism of action. We also demonstrate that, given its sampling speed, our method is well suited to explore structural transitions in a high-throughput manner, and can be used to determine functional conformational transitions at the entire proteome level.

引用

页码：116 / 126

页数：11

共 65 条

[11]

2-M

[12] Emerging methods in protein co-evolution [J].

de Juan, David ;

Pazos, Florencio ;

Valencia, Alfonso .

NATURE REVIEWS GENETICS, 2013, 14 (04) :249-261

[13] Biomolecular Simulation: A Computational Microscope for Molecular Biology [J].

Dror, Ron O. ;

Dirks, Robert M. ;

Grossman, J. P. ;

Xu, Huafeng ;

Shaw, David E. .

ANNUAL REVIEW OF BIOPHYSICS, VOL 41, 2012, 41 :429-452

[14] Enzyme dynamics during catalysis [J].

Eisenmesser, EZ ;

Bosco, DA ;

Akke, M ;

Kern, D .

SCIENCE, 2002, 295 (5559) :1520-1523

[15] Long-timescale simulation methods [J].

Elber, R .

CURRENT OPINION IN STRUCTURAL BIOLOGY, 2005, 15 (02) :151-156

[16] A milestoning study of the kinetics of an allosteric transition:: Atomically detailed simulations of deoxy Scapharca hemoglobin [J].

Elber, Ron .

BIOPHYSICAL JOURNAL, 2007, 92 (09) :L85-L87

[17] Atomically detailed simulation of the recovery stroke in myosin by Milestoning [J].

Elber, Ron ;

West, Anthony .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (11) :5001-5005

[18] Exploring the suitability of coarse-grained techniques for the representation of protein dynamics [J].

Emperador, Agusti ;

Carrillo, Oliver ;

Rueda, Manuel ;

Orozco, Modesto .

BIOPHYSICAL JOURNAL, 2008, 95 (05) :2127-2138

[19] United-Atom Discrete Molecular Dynamics of Proteins Using Physics-Based Potentials [J].

Emperador, Agusti ;

Meyer, Tim ;

Orozco, Modesto .

JOURNAL OF CHEMICAL THEORY AND COMPUTATION, 2008, 4 (12) :2001-2010

[20] Structural aspects of protein kinase control - role of conformational flexibility [J].

Engh, RA ;

Bossemeyer, D .

PHARMACOLOGY & THERAPEUTICS, 2002, 93 (2-3) :99-111

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