The European Physical Journal B ( IF 1.6 ) Pub Date : 2021-07-20 , DOI: 10.1140/epjb/s10051-021-00157-0 A Sofia F Oliveira 1, 2 , Giovanni Ciccotti 3, 4, 5 , Shozeb Haider 6 , Adrian J Mulholland 1
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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 \(\upbeta \)-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
中文翻译：
动态非平衡分子动力学揭示了生物分子系统中变构和信号传播的结构基础
摘要
Ciccotti 等人在 1970 年代提出的非平衡分子动力学 (D-NEMD) 的动力学方法正在复兴，并且在生物大分子研究中的影响越来越大。这种 D-NEMD 方法结合了静止（特别是平衡）和非平衡条件下的 MD 模拟，允许使用 Kubo-Onsager 关系确定系统的时间相关结构响应。除了提供系统对外部扰动的动态结构响应的详细图片外，这种方法还具有可以评估响应的统计显着性的优点。D-NEMD 方法最近已被用于确定烟碱型乙酰胆碱受体中域间信号传播的一般机制，以及在\(\upbeta \) -内酰胺酶，例如。它是平衡 MD 的补充，是一种非常有前途的识别和分析变构效应的方法。在这里，我们回顾了 D-NEMD 方法及其在生物分子系统中的应用，包括转运蛋白、受体和酶。
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