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Predicting Protein Dynamics and Allostery Using Multi-Protein Atomic Distance Constraints

Greener, JG; Filippis, I; Sternberg, MJE; (2017) Predicting Protein Dynamics and Allostery Using Multi-Protein Atomic Distance Constraints. Structure , 25 (3) pp. 546-558. 10.1016/j.str.2017.01.008. Green open access

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Abstract

The related concepts of protein dynamics, conformational ensembles and allostery are often 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 often cannot span large conformational changes. For T4-lysozyme, ExProSE is able to generate ensembles that are more native-like than tCONCOORD and NMSim, and comparable with 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.

Type: Article
Title: Predicting Protein Dynamics and Allostery Using Multi-Protein Atomic Distance Constraints
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.str.2017.01.008
Publisher version: https://doi.org/10.1016/j.str.2017.01.008
Language: English
Additional information: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: distance geometry, ensemble, allostery, protein dynamics, T4-lysozyme, cyclin-dependent kinase 2, catabolite activator protein, stochastic proximity embedding
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Computer Science
URI: http://discovery.ucl.ac.uk/id/eprint/10060280
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