A method to determine dielectric constants in nonhomogeneous systems: Application to biological membranes
A method to determine dielectric constants in nonhomogeneous systems: Application to biological membranes
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DOI：
10.1529/biophysj.107.117770
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发表时间：
2008-02-15
影响因子：
3.4
通讯作者：
Zhou, Huan-Xiang
中科院分区：
文献类型：
--
作者：
Nymeyer, Hugh;Zhou, Huan-Xiang
连续统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，对于如何在混合非均匀体系中分配介电常数仍然存在重大分歧。我们介绍了一种确定位置相关介电系数的方法。从分子动力学模拟。在这种方法中，引入测试电荷的自由能通过两种方式计算：从自由能摄动计算和从泊松方程的数值解计算。然后通过最小化这两个计算之间的差异来确定系统的介电剖面，同时用于测试电荷的多个位置。我们用这种方法来测定介电系数。被水包围的脂质双分子层的一部分。我们发现与其他方法得到的脂质双分子层的介电模型有很好的一致性。原子模拟计算的离子从散装水转移到脂质双分子层的自由能表明，当双分子层被表示为嵌入高介电溶剂中的单个低介电板时，会引入较大的误差。通过在低介电磁芯的每侧引入额外的中间介电层（类似于3），从类似于12埃延伸到18埃，可以得到显著的改进。脂质头基团外的传递自由能的微小下降表明存在非常高的介电。这些结果对隐式膜模型的设计和我们对蛋白质-膜相互作用的理解具有启示意义。
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 pro. le 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 pro. le 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 (similar to 3) on each side of the low dielectric core extending from similar to 12 angstrom to 18 angstrom. 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.