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Abstract：
The voltage-dependent anion channel (VDAC) forms the major pore in the outer mitochondrial membrane. Its high conducting open state features a moderate anion selectivity. There is some evidence indicating that the electrophysiological properties of VDAC vary with the salt concentration. Using a theoretical approach the molecular basis for this concentration dependence was investigated. Molecular dynamics simulations and continuum electrostatic calculations performed on the mouse VDAC1 isoform clearly demonstrate that the distribution of fixed charges in the channel creates an electric field, which determines the anion preference of VDAC at low salt concentration. Increasing the salt concentration in the bulk results in a higher concentration of ions in the VDAC wide pore. This event induces a large electrostatic screening of the charged residues promoting a less anion selective channel. Residues that are responsible for the electrostatic pattern of the channel were identified using the molecular dynamics trajectories. Some of these residues are found to be conserved suggesting that ion permeation between different VDAC species occurs through a common mechanism. This inference is buttressed by electrophysiological experiments performed on bean VDAC32 protein akin to mouse VDAC.
摘要：
电压依赖性阴离子通道(VDAC)形成线粒体外膜中的主要孔。其高导电开放状态具有中等的阴离子选择性。有一些证据表明VDAC的电生理特性随盐浓度而变化。使用理论方法研究了这种浓度依赖性的分子基础。对小鼠VDAC1同工型进行的分子动力学模拟和连续静电计算清楚地表明，通道中固定电荷的分布会产生电场，这决定了VDAC在低盐浓度下的阴离子偏好。增加主体中的盐浓度导致在VDAC宽孔中更高的离子浓度。该事件引起带电残基的大的静电屏蔽,促进较少阴离子选择性通道。使用分子动力学轨迹识别负责通道的静电模式的残基。发现这些残基中的一些是保守的，表明不同VDAC物种之间的离子渗透是通过共同的机制发生的。对类似于小鼠VDAC的豆VDAC32蛋白进行的电生理实验支持了这一推论。
