Computational Biomolecular Dynamics Group, Max Planck Institute for Multidisciplinary Sciences, Göttingen 37077, Germany.
J Chem Theory Comput. 2023 May 9;19(9):2574-2589. doi: 10.1021/acs.jctc.3c00061. Epub 2023 Apr 11.
Potassium channels are responsible for the selective yet efficient permeation of potassium ions across cell membranes. Despite many available high-resolution structures of potassium channels, those conformations inform only on static information on the ion permeation processes. Here, we use molecular dynamics simulations and Markov state models to obtain dynamical details of ion permeation. The permeation cycles, expressed in terms of selectivity filter occupancy and representing ion permeation events, are illustrated. We show that the direct knock-on permeation represents the dominant permeation mechanism over a wide range of potassium concentrations, temperatures, and membrane voltages for the pore of MthK. Direct knock-on is also observed in other potassium channels with a highly conserved selectivity filter, demonstrating the robustness of the permeation mechanism. Lastly, we investigate the charge strength dependence of permeation cycles. Our results shed light on the underlying permeation details, which are valuable in studying conduction mechanisms in potassium channels.
钾通道负责选择性但高效地跨细胞膜渗透钾离子。尽管有许多可用的钾通道高分辨率结构，但这些构象仅提供关于离子渗透过程的静态信息。在这里，我们使用分子动力学模拟和马科夫状态模型来获得离子渗透的动态细节。渗透循环，以选择性过滤器占有率表示，并代表离子渗透事件，被说明。我们表明，直接撞击渗透代表了在广泛的钾浓度、温度和膜电压范围内的主要渗透机制，对于 MthK 的孔。在具有高度保守的选择性过滤器的其他钾通道中也观察到直接撞击渗透，证明了渗透机制的稳健性。最后，我们研究了渗透循环的电荷强度依赖性。我们的结果揭示了潜在的渗透细节，这对于研究钾通道中的传导机制是有价值的。
