https://doi.org/10.1140/epjb/s10051-021-00157-0
Topical Review - Computational Methods
Dynamical nonequilibrium molecular dynamics reveals the structural basis for allostery and signal propagation in biomolecular systems
1
School of Chemistry, Centre for Computational Chemistry, University of Bristol, BS8 1TS, Bristol, UK
2
BrisSynBio, Life Sciences Building, Tyndall Avenue, BS8 1TQ, Bristol, UK
3
Institute for Applied Computing “Mauro Picone” (IAC), CNR, Via dei Taurini 19, 00185, Rome, Italy
4
School of Physics, University College of Dublin, UCD-Belfield, Dublin 4, Ireland
5
Università di Roma La Sapienza, Ple. A. Moro 5, 00185, Rome, Italy
6
School of Pharmacy, University College London, WC1N 1AX, London, UK
a
sofia.oliveira@bristol.ac.uk
d
adrian.mulholland@bristol.ac.uk
Received:
19
April
2021
Accepted:
5
July
2021
Published online:
20
July
2021
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 
-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.
© The Author(s) 2021
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