King's College London, London, United Kingdom.
University of Siena, Siena, Italy.
Curr Top Membr. 2016;78:183-214. doi: 10.1016/bs.ctm.2015.12.002. Epub 2016 Mar 14.
The permeation of ions and other molecules across biological membranes is an inherent requirement of all cellular organisms. Ion channels, in particular, are responsible for the conduction of charged species, hence modulating the propagation of electrical signals. Despite the universal physiological implications of this property, the molecular functioning of ion channels remains ambiguous. The combination of atomistic structural data with computational methodologies, such as molecular dynamics (MD) simulations, is now considered routine to investigate structure-function relationships in biological systems. A fuller understanding of conduction, selectivity, and gating, therefore, is steadily emerging due to the applicability of these techniques to ion channels. However, because their structure is known at atomic resolution, studies have consistently been biased toward K(+) channels, thus the molecular determinants of ionic selectivity, activation, and drug blockage in Na(+) channels are often overlooked. The recent increase of available crystallographic data has eminently encouraged the investigation of voltage-gated sodium (NaV) channels via computational methods. Here, we present an overview of simulation studies that have contributed to our understanding of key principles that underlie ionic conduction and selectivity in Na(+) channels, in comparison to the K(+) channel analogs.
离子和其他分子跨生物膜的渗透是所有细胞生物的固有要求。特别是离子通道，负责传导带电物质，因此调节电信号的传播。尽管这种特性具有普遍的生理意义，但离子通道的分子功能仍然不清楚。将原子结构数据与计算方法（如分子动力学 (MD) 模拟）相结合，现在被认为是研究生物系统结构-功能关系的常规方法。由于这些技术在离子通道中的适用性，因此对传导、选择性和门控的理解正在稳步提高。然而，由于其结构在原子分辨率下是已知的，因此研究一直偏向于 K(+) 通道，因此 Na(+) 通道中离子选择性、激活和药物阻断的分子决定因素经常被忽视。最近可用晶体学数据的增加极大地鼓励了通过计算方法研究电压门控钠 (NaV) 通道。在这里，我们概述了模拟研究，这些研究有助于我们理解离子在 Na(+) 通道中传导和选择性的关键原理，并与 K(+) 通道类似物进行了比较。
