COMPUTATIONAL STUDIES OF SOLVATION OF BIOMOLECULES

我们工作的总目标是加深对 生物学中结构与功能的关系 分子。该提案侧重于溶剂化的能量学。 对一系列生物重要系统的影响。这个 我们开发和应用的方法是基于宏观的 已在其显微镜下平均的溶剂的描述 各州。它假定水化的总热焓是 分子与分子间的静电相互作用的焓 非阳离子分子的溶剂和水化热 在溶剂中形成相同的空腔。一种新的反应场 用自洽方法处理溶质-溶剂相互作用 溶质和溶剂之间的边界定义为 用于计算静电对热焓的贡献。 量子化学或半经验拟合法被用来 描述溶质的电荷分布。改进 电荷分布的表示及其改进 正在引入具有大基数集的计算，并 探索过了。非静电性对水化的贡献 通过对实验数据的插补，引入了焓的概念 非极性标度粒子理论的结果或结果 分子。经验相关性与简单统计 力学计算将用于水合作用的评估。 以获得水合自由能的熵。方法将是 通过对溶剂化效应具有 都是通过实验测量的。其中包括溶剂化 小离子和各种极性分子的能量，pK 神经递质和蛋白质的差异，以及 水与其他极性或非极性溶剂之间的转移。 计划应用于具有溶剂化效应的其他系统 很可能很重要，包括对氢的计算 键合、离子缔合、离子与载体的结合、螺旋线圈 跃迁，以及静电对氢气速率的影响 蛋白质表面的交换。

The general goal of our work is to further the understanding of the relation between structure and fuction in biological molecules. The proposal focuses on the energetics of solvation effects in a range of biologically important systems. The approach we develop and apply is based on a macroscopic description of solvent already averaged over its microscopic states. It assumes that the total enthalpy of hydration is the sum of the enthalpy of electrostatic interactions of the molecule with the solvent and of the hydration enthalpy of a nonplar molecule forming the same cavity in the solvent. A new reaction field treatment of the solute-solvent interactions with a self-consistent definition of the boundary between the solute and the solvent are used to calculate the electrostatic contribution to the enthalpy. Quantum chemical or semiempirical fitting procedures are used to describe the charge distribution of the solute. Improved representation of the charge distributions as well as improved calculations with large basis sets are being introduced and explored. The non-electrostatic contributions to the hydration enthalpy are introduced through interpolation of experimental results or results of the scaled particle theory for nonpolar molecules. Empirical correlations and simple statistical mechanical calculations will serve in the evaluation of hydration entropy to obtain free energies of hydration. The methods will be tested by applications to systems for which solvation effects have been measured experimentally. These include the solvation energies of small ions and a variety of polar molecules, pK differences in neurotransmitters and proteins, and energies of transfer between water and other polar or non polar solvents. Planned applications to other systems in which solvation effects are likely to be important include calculations on hydrogen bonding, ionic association, ion binding to carriers, helix-coil transitions, and the electrostatic effects on the rate of hydrogen exchange on the surface of proteins.