ACCURATE CALCULATION OF HYDRATION FREE-ENERGIES USING MACROSCOPIC SOLVENT MODELS
ACCURATE CALCULATION OF HYDRATION FREE-ENERGIES USING MACROSCOPIC SOLVENT MODELS
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DOI：
10.1021/j100058a043
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发表时间：
1994-02-17
影响因子：
--
通讯作者：
HONIG, B
中科院分区：
文献类型：
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作者：
SITKOFF, D;SHARP, KA;HONIG, B
描述了一种可以快速准确计算水合自由能的方法和参数化方案。溶质被视为由分子表面定义的形状的可极化空腔，在原子核位置包含点电荷。静电对溶剂化的贡献源自：泊松方程的有限差分解（FDPB 方法）。非极性（空腔/范德华）能量作为表面积相关项添加，并具有源自水中碳氢化合物溶解度的单一表面张力系数（γ）。原子电荷和半径是通过修改现有的力场或量子力学导出的值，通过拟合小有机分子的实验溶剂化能来获得的。专门为 FDPB/gamma 方法开发了一个新的简单参数集（溶剂化能参数，PARSE），通过选择原子电荷和半径来重现对简单官能团溶剂化的估计贡献。 PARSE 参数再现了 67 个分子测试集的水合自由能，平均误差为 0.4 kcal/mol。对于氨基酸侧链和肽主链类似物，平均误差仅为 0.1 kcal/mol。
A method and parametrization scheme which allow fast and accurate calculations of hydration free energies are described. The solute is treated as a polarizable cavity of a shape defined by the molecular surface, containing point charges at the location of atomic nuclei. Electrostatic contributions to solvation are derived from:finite difference solutions of the Poisson equation (FDPB method). Nonpolar (cavity/van der Waals) energies are added as a surface area dependent term, with a single surface tension coefficient (gamma) derived from hydrocarbon solubility in water. Atomic charges and radii are obtained by modifying existing force-field or quantum-mechanically-derived values, by fitting to experimental solvation energies of small organic molecules. A new, simple parameter set (parameters for solvation energy, PARSE) is developed specifically for the FDPB/gamma method, by choosing atomic charges and radii which reproduce the estimated contributions to solvation of simple functional groups. The PARSE parameters reproduce hydration free energies for a test set of 67 molecules with an average error of 0.4 kcal/mol. For amino acid side chain and peptide backbone analogs the average error is only 0.1 kcal/mol.