Computational studies of transport in ion channels using metadynamics
Computational studies of transport in ion channels using metadynamics
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DOI：
10.1016/j.bbamem.2016.02.015
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发表时间：
2016-07-01
影响因子：
3.4
通讯作者：
Domene, Carmen
中科院分区：
文献类型：
--
作者：
Furini, Simone;Domene, Carmen
分子动力学模拟通过在原子水平上提供对复杂系统的结构和动力学的见解，在许多科学领域发挥了重要作用。然而，在大多数情况下，标准分子动力学的详尽抽样在计算上是禁止的，并且可获得的时间尺度仍然明显短于许多感兴趣的生物过程。特别是在离子通道的研究中，描述渗透和门控的真实模型需要考虑大量的粒子和精确的相互作用势，这严重限制了模拟的长度。为了克服这些限制，提出了几种先进的方法，其中包括元动力学。在该算法中，引入了一个外部偏置电位来加速沿选定的集体变量的采样。这种潜在的偏见阻碍了对已经探索过的构型空间的访问。此外，偏差势提供了自由能的估计，作为一旦模拟收敛所选择的集体变量的函数。在这篇综述中，讨论了元动力学在离子通道领域的最新贡献，包括如何使用元动力学来搜索过渡态，预测渗透途径，处理门控和渗透之间耦合的构象柔韧性，或计算渗透剖面的自由能。本文是《膜蛋白》特刊的一部分，由J.C. Gumbart和Sergei Noskov编辑。(C) 2016 Elsevier B.V.版权所有
Molecular dynamics simulations have played a fundamental role in numerous fields of science by providing insights into the structure and dynamics of complex systems at the atomistic level. However, exhaustive sampling by standard molecular dynamics is in most cases computationally prohibitive, and the time scales accessible remain significantly shorter than many biological processes of interest. In particular, in the study of ion channels, realistic models to describe permeation and gating require accounting for large numbers of particles and accurate interaction potentials, which severely limits the length of the simulations. To overcome such limitations, several advanced methods have been proposed among which is metadynamics. In this algorithm, an external bias potential to accelerate sampling along selected collective variables is introduced. This bias potential discourages visiting regions of the configurational space already explored. In addition, the bias potential provides an estimate of the free energy as a function of the collective variables chosen once the simulation has converged. In this review, recent contributions of metadynamics to the field of ion channels are discussed, including how metadynamics has been used to search for transition states, predict permeation pathways, treat conformational flexibility that underlies the coupling between gating and permeation, or compute free energy of permeation profiles. This article is part of a Special Issue entitled: Membrane Proteins edited by J.C. Gumbart and Sergei Noskov. (C) 2016 Elsevier B.V. All rights reserved.