COMPUTATIONAL STUDIES OF SOLVATION OF BIOMOLECULES

我们工作的总目标是进一步了解 生物学中结构与功能关系 分子。 该建议侧重于溶剂化的能量学 影响一系列重要的生物系统。 的 我们开发和应用的方法是基于宏观的 溶剂的描述已经在其显微镜下平均 states. 它假定总水合焓是 静电相互作用的焓 溶剂和非线性分子的水化焓 在溶剂中形成相同的空腔。 一个新的反应场 溶质-溶剂相互作用的自洽处理 溶质和溶剂之间的边界的定义是 用于计算静电对焓的贡献。 量子化学或半经验拟合程序用于 描述溶质的电荷分布。 改进 电荷分布的表示以及改进的 正在引入具有大基组的计算， 探讨了 非静电对水化的贡献 通过实验数据插值引入焓 非极性的标度粒子理论的结果 分子。 经验相关性和简单统计 力学计算将用于评价水化作用 熵，以获得水合自由能。 方法将是 通过应用于溶剂化效应具有 被实验测量。 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， 在水和其它极性或非极性溶剂之间的转移。 计划应用于溶剂化效应的其他系统 包括对氢的计算 成键，离子缔合，离子与载体结合，螺旋-卷曲 跃迁，以及静电对氢的速率的影响 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.