Department of Chemistry, Carnegie Mellon University, Pittsburgh, Pennsylvania 15213, USA.
J Phys Chem B. 2010 Nov 25;114(46):15180-90. doi: 10.1021/jp1046062. Epub 2010 Oct 28.
A soft repulsion (SR) model of short-range interactions between mobile ions and protein atoms is introduced in the framework of continuum representation of the protein and solvent. The Poisson-Nernst-Plank (PNP) theory of ion transport through biological channels is modified to incorporate this soft wall protein model. Two sets of SR parameters are introduced. The first is parametrized for all essential amino acid residues using all atom molecular dynamic simulations; the second is a truncated Lennard-Jones potential. We have further designed an energy-based algorithm for the determination of the ion accessible volume, which is appropriate for a particular system discretization. The effects of these models of short-range interactions were tested by computing current-voltage characteristics of the α-hemolysin channel. The introduced SR potentials significantly improve prediction of channel selectivity. In addition, we studied the effect of the choice of some space-dependent diffusion coefficient distributions on the predicted current-voltage properties. We conclude that the diffusion coefficient distributions largely affect total currents and have little effect on rectifications, selectivity, or reversal potential. The PNP-SR algorithm is implemented in a new efficient parallel Poisson, Poisson-Boltzmann, and PNP equation solver, also incorporated in a graphical molecular modeling package HARLEM.
引入了一种软斥力（SR）模型，用于描述可移动离子与蛋白质原子之间的短程相互作用，该模型基于蛋白质和溶剂的连续体表示。对通过生物通道的离子输运的泊松-纳斯特-普朗克（PNP）理论进行了修正，以纳入这种软壁蛋白质模型。引入了两组 SR 参数。第一组是使用全原子分子动力学模拟针对所有必需氨基酸残基进行参数化的；第二组是截断的 Lennard-Jones 势能。我们进一步设计了一种基于能量的算法，用于确定离子可及体积，该算法适用于特定的系统离散化。通过计算α-溶血素通道的电流-电压特性来测试这些短程相互作用模型的效果。引入的 SR 势显著改善了通道选择性的预测。此外，我们研究了一些空间相关扩散系数分布的选择对预测电流-电压特性的影响。我们得出结论，扩散系数分布在很大程度上影响总电流，而对整流、选择性或反转电位的影响很小。PNP-SR 算法在一个新的高效并行泊松、泊松-玻尔兹曼和 PNP 方程求解器中实现，也被纳入图形分子建模包 HARLEM 中。
