KcsA钾通道的多级开放过程:靶向分子动力学模拟  

Multi-stage opening of KcsA potassium channel by targeted molecular dynamics simulation

作　　者：钟文宇[1] 郭万林[1] 

机构地区：[1]南京航空航天大学纳米科学研究所,南京210016

出　　处：《计算力学学报》2009年第4期471-476,共6页Chinese Journal of Computational Mechanics

基　　金：国家自然科学基金(10802037;10372044);教育部创新团队(IRT0534);江苏省科技项目前期预研(BK2005217);江苏省自然科学基金创新学者攀登(BK2008042);江苏省博士后资助计划(0802015C)资助项目

摘　　要：钾通道晶体结构的获得为从结构和计算两方面去探索其原子层次的结构-功能关系提供了机会。钾通道门控过程的构型变化是这些正在探索的领域之一。但是发生在微秒层次的钾通道构型动态变化仍不清楚。本文对嵌入在水和磷脂双分子层中的KcsA钾通道进行了以Kv1.2钾通道开式结构为靶子的靶向分子动力学研究来探索其开放的动态细节。模拟中外加的开放驱动能量被降到了实验水平同一量级,模拟时间达到了150纳秒。发现通道以多级阶梯的方式开放。共观察到两级阶梯,每级包括一个扩张态和一个准稳定态。可以推断,在生理过程更长的时间历程中,会有更多级的阶梯出现。Determinations of crystal structures of potassium channels provide opportunities to integrate structural and computational studies to resolve the atomic relationship between the structure and the function of potassium channels. The conformational change underlying the gating process of potassium channels is one of the areas have been investigated. However, the dynamic process underlying the conformational changes, which are on a time scale of microsecond, are still obscured. Here targeted molecular dynamics simulations of KcsA K^＋ channel embedded in a solvated lipid bilayer, with the open Kv1. 2 structure serving as targeted conformation, are performed to investigate the detailed dynamic opening process. The artificial gating energy is lowered down to the order of that in experimental cases and the running time is up to 150 ns. Thus the channel opens in a multi-stage way. Two stages are observed, each consists of an expanding phase and a quasi-stable phase. It is possible that more stages will exist in a real gating process with much longer time course.

关 键 词：钾通道 门控 蛋白质 分子动力学模拟 KCSA Kv1.2 

分 类 号：Q66[生物学—生物物理学] Q71