Department of Biochemistry and Molecular Biology, Gordon Center for Integrative Science, The University of Chicago, Chicago, IL 60637.
J Gen Physiol. 2013 Oct;142(4):465-75. doi: 10.1085/jgp.201311014.
A computational method is developed to allow molecular dynamics simulations of biomembrane systems under realistic ionic gradients and asymmetric salt concentrations while maintaining the conventional periodic boundary conditions required to minimize finite-size effects in an all-atom explicit solvent representation. The method, which consists of introducing a nonperiodic energy step acting on the ionic species at the edge of the simulation cell, is first tested with illustrative applications to a simple membrane slab model and a phospholipid membrane bilayer. The nonperiodic energy-step method is then used to calculate the reversal potential of the bacterial porin OmpF, a large cation-specific β-barrel channel, by simulating the I-V curve under an asymmetric 10:1 KCl concentration gradient. The calculated reversal potential of 28.6 mV is found to be in excellent agreement with the values of 26-27 mV measured from lipid bilayer experiments, thereby demonstrating that the method allows realistic simulations of nonequilibrium membrane transport with quantitative accuracy. As a final example, the pore domain of Kv1.2, a highly selective voltage-activated K(+) channel, is simulated in a lipid bilayer under conditions that recreate, for the first time, the physiological K(+) and Na(+) concentration gradients and the electrostatic potential difference of living cells.
开发了一种计算方法，允许在现实的离子梯度和不对称盐浓度下对生物膜系统进行分子动力学模拟，同时保持传统的周期性边界条件，以最小化全原子显式溶剂表示中的有限尺寸效应。该方法包括在模拟单元的边缘对离子物种施加非周期性能量步，首先通过对简单的膜片模型和磷脂双层膜的说明性应用进行测试。然后，通过在不对称的 10:1 KCl 浓度梯度下模拟 I-V 曲线，使用非周期性能量步方法计算细菌孔蛋白 OmpF（一种大阳离子特异性β桶通道）的反转电位。计算得到的反转电位为 28.6 mV，与从脂质双层实验测量得到的 26-27 mV 值非常吻合，从而证明该方法可以以定量精度对非平衡膜转运进行现实模拟。作为最后一个例子，在脂质双层中模拟 Kv1.2（一种高度选择性的电压激活 K(+)通道）的孔域，首次在生理 K(+)和 Na(+)浓度梯度以及活细胞的静电位差的条件下进行模拟。
