Accuracy of binding free energy calculations utilizing implicit solvent models is critically affected by parameters of the underlying dielectric boundary, specifically, the atomic and water probe radii. Here, a multidimensional optimization pipeline is used to find optimal atomic radii, specifically for binding calculations in the implicit solvent. To reduce overfitting, the optimization target includes separate, weighted contributions from both binding and hydration free energies. The resulting five-parameter radii set, OPT_BIND5D, is evaluated against experiment for binding free energies of 20 host-guest (H-G) systems, unrelated to the types of structures used in the training. The resulting accuracy for this H-G test set (root mean square error of 2.03 kcal/mol, mean signed error of -0.13 kcal/mol, mean absolute error of 1.68 kcal/mol, and Pearson's correlation of r = 0.79 with the experimental values) is on par with what can be expected from the fixed charge explicit solvent models. Best agreement with the experiment is achieved when the implicit salt concentration is set equal or close to the experimental conditions.

中文翻译：

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在隐式溶剂中绑定自由能估计的最佳介电边界。


利用隐式溶剂模型进行绑定自由能计算的准确性受到底层介电边界参数的严重影响，特别是原子和水探针半径。在这里，多维优化管道用于查找最佳原子半径，特别是用于隐式溶剂中的绑定计算。为了减少过拟合，优化目标包括来自结合能和水合自由能的单独加权贡献。所得的五参数半径集 OPT_BIND5D 根据 20 个主客体 （H-G） 系统的结合自由能实验进行评估，这些系统与训练中使用的结构类型无关。该 H-G 测试集的结果精度（均方根误差为 2.03 kcal/mol，平均符号误差为 -0.13 kcal/mol，平均绝对误差为 1.68 kcal/mol，皮尔逊相关性 r = 0.79 与实验值）与固定电荷显式溶剂模型的预期相当。当隐含盐浓度设置为等于或接近实验条件时，与实验的最佳一致性。