Topical Review - Computational Methods
Dynamical nonequilibrium molecular dynamics reveals the structural basis for allostery and signal propagation in biomolecular systems
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
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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