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Predicting protein dynamics and allostery using multi-protein atomic distance constraints

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Title: Predicting protein dynamics and allostery using multi-protein atomic distance constraints
Authors: Greener, JG
Filippis, I
Sternberg, MJE
Item Type: Journal Article
Abstract: The related concepts of protein dynamics, conformational ensembles and allostery are of- ten difficult to study with molecular dynamics (MD) due to the timescales involved. We present ExProSE (Exploration of Protein Structural Ensembles), a distance geometry-based method that generates an ensemble of protein structures from two input structures. ExProSE provides a unified framework for the exploration of protein structure and dynamics in a fast and accessible way. Using a dataset of apo/holo pairs it is shown that existing coarse-grained methods can often not span large conformational changes. For T4-lysozyme ExProSE is able to generate ensembles that are more native-like than tCONCOORD and NMSim, and com- parable to targeted MD. By adding additional constraints representing potential modulators, ExProSE can predict allosteric sites. ExProSE ranks an allosteric pocket first or second for 27 out of 58 allosteric proteins, which is similar and complementary to existing methods. The ExProSE source code is freely-available.
Issue Date: 9-Feb-2017
Date of Acceptance: 20-Dec-2016
URI: http://hdl.handle.net/10044/1/43553
DOI: https://dx.doi.org/10.1016/j.str.2017.01.008
ISSN: 1878-4186
Publisher: Elsevier (Cell Press)
Start Page: 546
End Page: 558
Journal / Book Title: Structure
Volume: 25
Issue: 3
Copyright Statement: © 2017 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Sponsor/Funder: Biotechnology and Biological Sciences Research Council
Keywords: Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Biophysics
Cell Biology
RELEVANT CONFORMATIONAL TRANSITIONS
BINDING-SITES
WEB SERVER
DISCOVERY
MOTIONS
FLUCTUATIONS
INHIBITORS
ENSEMBLES
DOCKING
ENZYMES
T4-lysozyme
allostery
catabolite activator protein
cyclin-dependent kinase 2
distance geometry
ensemble
protein dynamics
stochastic proximity embedding
06 Biological Sciences
08 Information And Computing Sciences
03 Chemical Sciences
Publication Status: Published
Appears in Collections:Faculty of Natural Sciences



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