In this study quantum mechanical methods were used to predict the solvation energies of a series of drug-like molecules both in water and in octanol, in the context of the SAMPL6 n-octanol/water partition coefficient challenge. In pharmaceutical design, n-octanol/water partition coefficient, LogP, describes the drug's hydrophobicity and membrane permeability, thus, a well-established theoretical method that rapidly determines the hydrophobicity of a drug, enables the progress of the drug design. In this study, the solvation free energies were obtained via six different methodologies (B3LYP, M06-2X and ωB97XD functionals with 6-311+G** and 6-31G* basis sets) by taking into account the environment implicitly; the methodology chosen (B3LYP/6-311+G**) was used later to evaluate ΔGsolv by using explicit water as solvent. We optimized each conformer in different solvents separately, our calculations have shown that the stability of the conformers is highly dependent on the solvent environment. We have compared implicitly and explicitly solvated systems, the interaction of one explicit water with drug-molecules at the proper location leads to the prediction of more accurate LogP values.

中文翻译：

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SAMPL6的盲目挑战：通过DFT方法了解类药物分子的辛醇-水分配系数。

在这项研究中，在SAMPL6正辛醇/水分配系数挑战的背景下，量子力学方法被用来预测一系列药物样分子在水和辛醇中的溶剂化能。在药物设计中，正辛醇/水分配系数LogP描述了药物的疏水性和膜通透性，因此，一种迅速确定药物疏水性的公认理论方法可以促进药物设计的发展。在这项研究中，通过隐式考虑环境，通过六种不同的方法（具有6-311 + G **和6-31G *基集的B3LYP，M06-2X和ωB97XD官能团）获得了溶剂化自由能。稍后使用所选方法（B3LYP / 6-311 + G **）通过使用显性水作为溶剂来评估ΔGsolv。我们分别在不同溶剂中优化了每个构象异构体，我们的计算表明，构象异构体的稳定性高度依赖于溶剂环境。我们已经比较了隐式和显式溶剂化系统，一种显性水与药物分子在适当位置的相互作用导致预测更准确的LogP值。