Dynamical nonequilibrium molecular dynamics reveals the structural basis for allostery and signal propagation in biomolecular systems

A Sofia F Oliveira, Giovanni Ciccotti, Shozeb Haider, Adrian J Mulholland

Research output: Contribution to journalReview article (Academic Journal)peer-review

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Abstract

Abstract: A dynamical approach to nonequilibrium molecular dynamics (D-NEMD), proposed in the 1970s by Ciccotti et al., is undergoing a renaissance and is having increasing impact in the study of biological macromolecules. This D-NEMD approach, combining MD simulations in stationary (in particular, equilibrium) and nonequilibrium conditions, allows for the determination of the time-dependent structural response of a system using the Kubo-Onsager relation. Besides providing a detailed picture of the system's dynamic structural response to an external perturbation, this approach also has the advantage that the statistical significance of the response can be assessed. The D-NEMD approach has been used recently to identify a general mechanism of inter-domain signal propagation in nicotinic acetylcholine receptors, and allosteric effects in β -lactamase enzymes, for example. It complements equilibrium MD and is a very promising approach to identifying and analysing allosteric effects. Here, we review the D-NEMD approach and its application to biomolecular systems, including transporters, receptors, and enzymes.

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Original languageEnglish
Article number144
Pages (from-to)144
JournalEuropean Physical Journal B: Condensed Matter
Volume94
Issue number7
Early online date20 Jul 2021
DOIs
Publication statusPublished - 20 Jul 2021

Bibliographical note

Funding Information:
AJM and ASFO thank EPSRC (grant number EP/M022609/1). We also thank BrisSynBio, a BBSRC/EPSRC Synthetic Biology Research Centre (Grant Number:BB/L01386X/1) for funding ASFO. We thank Dr Joao Damas and Barbara Abreu for their help with Figs. and , respectively. We thank the Advanced Computing Research Centre, University of Bristol ( http://www.bris.ac.uk/acrc ) and Oracle for Research for computer time for simulations reviewed here. SH acknowledges a grant from the National Institutes of Health (USA) under award number RO1AI063517 and a Case studentship award from Astra Zeneca-EPSRC.

Funding Information:
AJM and ASFO thank EPSRC (grant number EP/M022609/1). We also thank BrisSynBio, a BBSRC/EPSRC Synthetic Biology Research Centre (Grant Number:BB/L01386X/1) for funding ASFO. We thank Dr Joao Damas and Barbara Abreu for their help with Figs. 3 and 4 , respectively. We thank the Advanced Computing Research Centre, University of Bristol (http://www.bris.ac.uk/acrc) and Oracle for Research for computer time for simulations reviewed here. SH acknowledges a grant from the National Institutes of Health (USA) under award number RO1AI063517 and a Case studentship award from Astra Zeneca-EPSRC.

Publisher Copyright:
© 2021, The Author(s).

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