Levy Ronald M, Zhang Linda Y, Gallicchio Emilio, Felts Anthony K
Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, New Jersey 08854, USA.
J Am Chem Soc. 2003 Aug 6;125(31):9523-30. doi: 10.1021/ja029833a.
Implicit solvent hydration free energy models are an important component of most modern computational methods aimed at protein structure prediction, binding affinity prediction, and modeling of conformational equilibria. The nonpolar component of the hydration free energy, consisting of a repulsive cavity term and an attractive van der Waals solute-solvent interaction term, is often modeled using estimators based on the solvent exposed solute surface area. In this paper, we analyze the accuracy of linear surface area models for predicting the van der Waals solute-solvent interaction energies of native and non-native protein conformations, peptides and small molecules, and the desolvation penalty of protein-protein and protein-ligand binding complexes. The target values are obtained from explicit solvent simulations and from a continuum solvent van der Waals interaction energy model. The results indicate that the standard surface area model, while useful on a coarse-grained scale, may not be accurate or transferable enough for high resolution modeling studies of protein folding and binding. The continuum model constructed in the course of this study provides one path for the development of a computationally efficient implicit solvent nonpolar hydration free energy estimator suitable for high-resolution structural and thermodynamic modeling of biological macromolecules.
隐式溶剂水化自由能模型是大多数旨在进行蛋白质结构预测、结合亲和力预测以及构象平衡建模的现代计算方法的重要组成部分。水化自由能的非极性部分由一个排斥性的空腔项和一个吸引性的范德华溶质 - 溶剂相互作用项组成，通常使用基于溶剂暴露溶质表面积的估计器进行建模。在本文中，我们分析了线性表面积模型预测天然和非天然蛋白质构象、肽和小分子的范德华溶质 - 溶剂相互作用能以及蛋白质 - 蛋白质和蛋白质 - 配体结合复合物去溶剂化惩罚的准确性。目标值来自显式溶剂模拟和连续介质溶剂范德华相互作用能模型。结果表明，标准表面积模型虽然在粗粒度尺度上有用，但对于蛋白质折叠和结合的高分辨率建模研究可能不够准确或缺乏足够的可转移性。在本研究过程中构建的连续介质模型为开发适用于生物大分子高分辨率结构和热力学建模的计算高效的隐式溶剂非极性水化自由能估计器提供了一条途径。
