Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, CA, USA.
Department of Pharmacology, School of Medicine, University of California, Davis, CA, USA.
J Physiol. 2019 Feb;597(3):679-698. doi: 10.1113/JP277088. Epub 2018 Dec 19.
Ion channels are implicated in many essential physiological events such as electrical signal propagation and cellular communication. The advent of K and Na ion channel structure determination has facilitated numerous investigations of molecular determinants of their behaviour. At the same time, rapid development of computer hardware and molecular simulation methodologies has made computational studies of large biological molecules in all-atom representation tractable. The concurrent evolution of experimental structural biology with biomolecular computer modelling has yielded mechanistic details of fundamental processes unavailable through experiments alone, such as ion conduction and ion channel gating. This review is a short survey of the atomistic computational investigations of K and Na ion channels, focusing on KcsA and several voltage-gated channels from the K and Na families, which have garnered many successes and engendered several long-standing controversies regarding the nature of their structure-function relationship. We review the latest advancements and challenges facing the field of molecular modelling and simulation regarding the structural and energetic determinants of ion channel function and their agreement with experimental observations.
离子通道参与许多重要的生理事件，如电信号的传播和细胞通讯。钾和钠离子通道结构测定的出现促进了对其行为的分子决定因素的大量研究。与此同时，计算机硬件和分子模拟方法的快速发展使得在全原子表示形式下对大型生物分子进行计算研究变得可行。实验结构生物学与生物分子计算机建模的共同发展，提供了仅通过实验无法获得的基本过程的机制细节，例如离子传导和离子通道门控。本文综述了钾和钠离子通道的原子计算研究，重点介绍了 KcsA 和钾和钠家族中的几个电压门控通道，这些通道取得了许多成功，并引发了关于其结构-功能关系性质的几个长期争议。我们回顾了分子建模和模拟领域在离子通道功能的结构和能量决定因素方面的最新进展和挑战，以及它们与实验观察结果的一致性。
