Nymeyer Hugh, Zhou Huan-Xiang
Department of Chemistry and Biochemistry, School of Computational Science, Florida State University, Tallahassee, Florida 32306, USA.
Biophys J. 2008 Feb 15;94(4):1185-93. doi: 10.1529/biophysj.107.117770. Epub 2007 Oct 19.
Continuum electrostatic models have had quantitative success in describing electrostatic-mediated phenomena on atomistic scales; however, there continues to be significant disagreement about how to assign dielectric constants in mixed, nonhomogeneous systems. We introduce a method for determining a position-dependent dielectric profile from molecular dynamics simulations. In this method, the free energy of introducing a test charge is computed two ways: from a free energy perturbation calculation and from a numerical solution to Poisson's Equation. The dielectric profile of the system is then determined by minimizing the discrepancy between these two calculations simultaneously for multiple positions of the test charge. We apply this method to determine the dielectric profile of a lipid bilayer surrounded by water. We find good agreement with dielectric models for lipid bilayers obtained by other approaches. The free energy of transferring an ion from bulk water to the lipid bilayer computed from the atomistic simulations indicates that large errors are introduced when the bilayer is represented as a single slab of low dielectric embedded in the higher-dielectric solvent. Significant improvement results from introducing an additional layer of intermediate dielectric ( approximately 3) on each side of the low dielectric core extending from approximately 12 A to 18 A. A small dip in transfer free energy just outside the lipid headgroups indicates the presence of a very high dielectric. These results have implications for the design of implicit membrane models and our understanding of protein-membrane interactions.
连续介质静电模型在描述原子尺度上的静电介导现象方面取得了定量成功；然而，在如何为混合的非均匀系统分配介电常数方面，仍然存在重大分歧。我们介绍了一种从分子动力学模拟中确定位置依赖介电分布的方法。在这种方法中，引入测试电荷的自由能通过两种方式计算：从自由能微扰计算和泊松方程的数值解。然后通过同时针对测试电荷的多个位置最小化这两种计算之间的差异来确定系统的介电分布。我们应用这种方法来确定被水包围的脂质双层的介电分布。我们发现与通过其他方法获得的脂质双层介电模型有很好的一致性。从原子模拟计算得出的将离子从本体水转移到脂质双层的自由能表明，当将双层表示为嵌入高介电溶剂中的低介电单平板时会引入很大误差。通过在低介电核心的每一侧引入从约12埃到18埃延伸的额外中间介电层（约为3）可得到显著改善。脂质头部基团外侧转移自由能的小下降表明存在非常高的介电常数。这些结果对隐式膜模型的设计以及我们对蛋白质 - 膜相互作用的理解具有启示意义。
