Blind predictions of octanol/water partition coefficients at 298 K for 11 kinase inhibitor fragment like compounds were made for the SAMPL6 challenge. We used the conventional, "untrained", free energy based approach wherein the octanol/water partition coefficient was computed directly as the difference in solvation free energy in water and 1-octanol. We additionally proposed and used two different forms of a "trained" approach. Physically, the goal of the trained approach is to relate the partition coefficient computed using pure 1-octanol to that using water-saturated 1-octanol. In the first case, we assumed the partition coefficient using water-saturated 1-octanol and pure 1-octanol are linearly correlated. In the second approach, we assume the solvation free energy in water-saturated 1-octanol can be written as a linear combination of the solvation free energy in pure water and 1-octanol. In all cases here, the solvation free energies were computed using electronic structure calculations in the SM12, SM8, and SMD universal solvent models. In the context of the present study, our results in general do not support the additional effort of the trained approach.

中文翻译：

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使用 SM12、SM8 和 SMD 溶剂化模型预测 SAMPL6 挑战的辛醇/水分配系数。

对于 SAMPL6 挑战，对 11 种激酶抑制剂片段样化合物在 298 K 下的辛醇/水分配系数进行了盲目预测。我们使用传统的、“未经训练的”、基于自由能的方法，其中辛醇/水分配系数直接计算为水和 1-辛醇中溶剂化自由能的差异。我们还提出并使用了两种不同形式的“训练有素”方法。在物理上，训练方法的目标是将使用纯 1-辛醇计算的分配系数与使用水饱和 1-辛醇计算的分配系数相关联。在第一种情况下，我们假设使用水饱和 1-辛醇和纯 1-辛醇的分配系数呈线性相关。在第二种方法中，我们假设水饱和的 1-辛醇中的溶剂化自由能可以写成纯水和 1-辛醇中的溶剂化自由能的线性组合。在此处的所有情况下，溶剂化自由能均使用 SM12、SM8 和 SMD 通用溶剂模型中的电子结构计算来计算。在本研究的背景下，我们的结果一般不支持训练方法的额外努力。