Chung Shin-Ho, Allen Toby W, Kuyucak Serdar
Department of Physics, Faculty of Sciences, Australian National University, Canberra, ACT 0200, Australia.
Biophys J. 2002 Feb;82(2):628-45. doi: 10.1016/S0006-3495(02)75427-1.
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 A to 5 A. Our simulation results reproduce several experimental observations, including the current-voltage curves, conductance-concentration relationships, and outward rectification of currents.
利用静电计算和三维布朗动力学模拟研究了离子通过钾通道运输的潜在机制。我们首先通过分子动力学模拟构建通道的开放态构型，将跨膜螺旋向外拉，直到通道达到所需的内部半径。为了深入了解离子渗透，我们构建了在存在其他驻留离子的情况下离子穿越通道时所经历的势能分布。这些分布表明，在没有外加电场的情况下，通道在稳定平衡中容纳三个钾离子，两个在选择性过滤器中，一个在中央腔中。在存在驱动电位的情况下，这种三离子状态变得不稳定，并观察到离子通过通道的渗透。这些定性解释得到了三维布朗动力学模拟结果的证实。我们发现，当细胞外入口附近的可电离残基完全带电而细胞内侧附近的可电离残基部分带电时，通道导通。当通道细胞内口的半径从2埃增加到5埃时，电导率急剧增加。我们的模拟结果重现了几个实验观察结果，包括电流-电压曲线、电导率-浓度关系以及电流的外向整流。
