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

doi:10.1140/epjb/s10051-021-00157-0

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 journal › Review article (Academic Journal) › peer-review

18 Citations (Scopus)

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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.

Graphic abstract:

Original language	English
Article number	144
Pages (from-to)	144
Journal	European Physical Journal B: Condensed Matter
Volume	94
Issue number	7
Early online date	20 Jul 2021
DOIs	https://doi.org/10.1140/epjb/s10051-021-00157-0
Publication status	Published - 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.

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© 2021, The Author(s).

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10.1140/epjb/s10051-021-00157-0

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CCP-BioSim: Biomolecular Simulation at the Life Sciences Interface
Mulholland, A. J. (Principal Investigator)
1/07/15 → 30/04/21
Project: Research

HPC (High Performance Computing) and HTC (High Throughput Computing) Facilities
Alam, S. R. (Manager), Williams, D. A. G. (Manager), Eccleston, P. E. (Manager) & Greene, D. (Manager)
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Cite this

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

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.Graphic abstract: ",

author = "Oliveira, {A Sofia F} and Giovanni Ciccotti and Shozeb Haider and Mulholland, {Adrian J}",

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: {\textcopyright} 2021, The Author(s).",

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Dynamical nonequilibrium molecular dynamics reveals the structural basis for allostery and signal propagation in biomolecular systems. / Oliveira, A Sofia F; Ciccotti, Giovanni; Haider, Shozeb et al.
In: European Physical Journal B: Condensed Matter, Vol. 94, No. 7, 144, 20.07.2021, p. 144.

Research output: Contribution to journal › Review article (Academic Journal) › peer-review

TY - JOUR

T1 - Dynamical nonequilibrium molecular dynamics reveals the structural basis for allostery and signal propagation in biomolecular systems

AU - Oliveira, A Sofia F

AU - Ciccotti, Giovanni

AU - Haider, Shozeb

AU - Mulholland, Adrian J

N1 - 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).

PY - 2021/7/20

Y1 - 2021/7/20

N2 - 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.Graphic abstract:

AB - 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.Graphic abstract:

U2 - 10.1140/epjb/s10051-021-00157-0

DO - 10.1140/epjb/s10051-021-00157-0

M3 - Review article (Academic Journal)

C2 - 34720710

SN - 1434-6028

VL - 94

SP - 144

JO - European Physical Journal B: Condensed Matter

JF - European Physical Journal B: Condensed Matter

IS - 7

M1 - 144

ER -

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

Abstract

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HPC (High Performance Computing) and HTC (High Throughput Computing) Facilities

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