Conducting-state properties of the KcsA potassium channel from molecular and Brownian dynamics simulations
Conducting-state properties of the KcsA potassium channel from molecular and Brownian dynamics simulations
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DOI：
10.1016/s0006-3495(02)75427-1
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发表时间：
2002-02-01
影响因子：
3.4
通讯作者：
Kuyucak, S
中科院分区：
文献类型：
--
作者：
Chung, SH;Allen, TW;Kuyucak, S
利用静电计算和三维布朗动力学模拟研究了离子跨钾通道的运输机制。我们首先建立开放状态配置的通道与分子动力学模拟，通过拉跨膜螺旋向外，直到通道达到所需的内部半径。为了深入了解离子渗透，我们构建了势能分布经历的离子穿越通道中存在的其他居民离子。这些配置文件显示，在没有外加场的情况下，通道容纳三个钾离子在一个稳定的平衡，两个在选择性过滤器和一个在中心腔。在驱动电位的存在下，这种三离子状态变得不稳定，并且观察到离子渗透穿过通道。这些定性的解释证实了三维布朗动力学模拟的结果。我们发现，当细胞外入口附近的可电离残基是完全带电的，而细胞内侧附近的部分带电时，通道进行。当通道的细胞内口的半径从2埃增加到5埃时，电导急剧增加。我们的模拟结果再现了几个实验观察，包括电流-电压曲线，电导-浓度关系，和电流的外向整流。
The mechanisms underlying transport of ions across the potassium channel are examined using electrostatic calculations and three-dimensional Brownian dynamics simulations. We first build open-state configurations of the channel with molecular dynamics simulations, by pulling the transmembrane helices outward until the channel attains the desired interior radius. To gain insights into ion permeation, we construct potential energy profiles experienced by an ion traversing the channel in the presence of other resident ions. These profiles reveal that in the absence of an applied field the channel accommodates three potassium ions in a stable equilibrium, two in the selectivity filter and one in the central cavity. In the presence of a driving potential, this three-ion state becomes unstable, and ion permeation across the channel is observed. These qualitative explanations are confirmed by the results of three-dimensional Brownian dynamics simulations. We find that the channel conducts when the ionizable residues near the extracellular entrance are fully charged and those near the intracellular side are partially charged. The conductance increases steeply as the radius of the intracellular mouth of the channel is increased from 2 Angstrom to 5 Angstrom. Our simulation results reproduce several experimental observations, including the current-voltage curves, conductance-concentration relationships, and outward rectification of currents.