Hassan Sergio A
Center for Molecular Modeling, DCB/CIT, National Institutes of Health, U.S. DHHS, Bethesda, Maryland 20892, USA.
J Phys Chem B. 2007 Jan 11;111(1):227-41. doi: 10.1021/jp0647479.
Molecular interactions in solution are controlled by the bulk medium and by the forces originating in the structured region of the solvent close to the solutes. In this paper, a model of electrostatic and liquid-structure forces for dynamics simulations of biomolecules is presented. The model introduces information on the microscopic nature of the liquid in the vicinity of polar and charged groups and the associated non-pairwise character of the forces, thus improving upon conventional continuum representations. The solvent is treated as a polar and polarizable medium, with dielectric properties described by an inhomogeneous version of the Onsager theory. This treatment leads to an effective position-dependent dielectric permittivity that incorporates saturation effects of the electric field and the spatial variation of the liquid density. The non-pairwise additivity of the liquid-structure forces is represented by centers of force located at specific points in the liquid phase. These out-of-the-solute centers are positioned at the peaks of liquid density and exert local, external forces on the atoms of the solute. The density is calculated from a barometric law, using a Lennard-Jones-type solute-liquid effective interaction potential. The conceptual aspects of the model and its exact numerical solutions are discussed for single alkali and halide ions and for ion-pair interactions. The practical aspects of the model and the simplifications introduced for efficient computation of forces in molecular solutes are discussed in the context of polar and charged amino acid dimers. The model reproduces the contact and solvent-separated minima and the desolvation barriers of intermolecular potentials of mean force of amino acid dimers, as observed in atomistic dynamics simulations. Possible refinements based on an improved treatment of molecular correlations are discussed.
溶液中的分子相互作用受整体介质以及源自溶剂中靠近溶质的结构化区域的力的控制。本文提出了一种用于生物分子动力学模拟的静电和液体结构力模型。该模型引入了关于极性和带电基团附近液体微观性质以及力的相关非成对特征的信息，从而改进了传统的连续介质表示法。溶剂被视为一种极性且可极化的介质，其介电性质由昂萨格理论的非均匀版本描述。这种处理导致了一种有效的位置依赖介电常数，它包含了电场的饱和效应和液体密度的空间变化。液体结构力的非成对加和性由位于液相特定点的力中心表示。这些溶质外的中心位于液体密度的峰值处，并对溶质的原子施加局部外力。密度由气压定律计算得出，使用的是 Lennard - Jones 型溶质 - 液体有效相互作用势。针对单个碱金属和卤离子以及离子对相互作用，讨论了该模型的概念方面及其精确数值解。在极性和带电氨基酸二聚体的背景下，讨论了该模型的实际方面以及为有效计算分子溶质中的力而引入的简化方法。该模型再现了氨基酸二聚体平均力分子间势的接触和溶剂分离最小值以及去溶剂化能垒，这与原子动力学模拟中观察到的结果一致。还讨论了基于对分子相关性的改进处理可能进行的优化。
