Exobiology Branch, MS 239-4, NASA Ames Research Center , Moffett Field, California 94035, United States.
Department of Pharmaceutical Chemistry University of California , San Francisco, California 94132, United States.
J Phys Chem B. 2017 Apr 20;121(15):3607-3619. doi: 10.1021/acs.jpcb.6b09598. Epub 2016 Dec 12.
We examine the validity and utility of the electrodiffusion (ED) equation, i.e., the generalized Nernst-Planck equation, to characterize, in combination with molecular dynamics, the electrophysiological behavior of simple ion channels. As models, we consider three systems-two naturally occurring channels formed by α-helical bundles of peptaibols, trichotoxin, and alamethicin, and a synthetic, hexameric channel, formed by a peptide that contains only leucine and serine. All these channels mediate transport of potassium and chloride ions. Starting with equilibrium properties, such as the potential of mean force experienced by an ion traversing the channel and diffusivity, obtained from molecular dynamics simulations, the ED equation can be used to determine the full current-voltage dependence with modest or no additional effort. The potential of mean force can be obtained not only from equilibrium simulations, but also, with comparable accuracy, from nonequilibrium simulations at a single voltage. The main assumptions underlying the ED equation appear to hold well for the channels and voltages studied here. To expand the utility of the ED equation, we examine what are the necessary and sufficient conditions for Ohmic and nonrectifying behavior and relate deviations from this behavior to the shape of the ionic potential of mean force.
我们检验了电扩散（ED）方程的有效性和实用性，即广义能斯特-普朗克方程，结合分子动力学来描述简单离子通道的电生理行为。作为模型，我们考虑了三个系统：两个由肽聚糖的α-螺旋束形成的天然通道、三毒素和短杆菌肽，以及一个由仅含有亮氨酸和丝氨酸的肽形成的合成六聚体通道。所有这些通道都介导钾离子和氯离子的转运。从分子动力学模拟中获得的离子穿过通道的平均力势和扩散率等平衡性质出发，ED 方程可以用于确定具有适度或无需额外努力的全电流-电压依赖性。平均力势不仅可以从平衡模拟中获得，而且还可以以相当的精度从单个电压下的非平衡模拟中获得。ED 方程的主要假设似乎对这里研究的通道和电压都适用。为了扩大 ED 方程的实用性，我们研究了欧姆和非整流行为的必要和充分条件，并将偏离这种行为与离子平均力势的形状联系起来。
