Johnson J, Case D A, Yamazaki T, Gusarov S, Kovalenko A, Luchko T
Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.
J Phys Condens Matter. 2016 Sep 1;28(34):344002. doi: 10.1088/0953-8984/28/34/344002. Epub 2016 Jul 1.
Implicit solvent models offer an attractive way to estimate the effects of a solvent environment on the properties of small or large solutes without the complications of explicit simulations. One common test of accuracy is to compute the free energy of transfer from gas to liquid for a variety of small molecules, since many of these values have been measured. Studies of the temperature dependence of these values (i.e. solvation enthalpies and entropies) can provide additional insights into the performance of implicit solvent models. Here, we show how to compute temperature derivatives of hydration free energies for the 3D-RISM integral equation approach. We have computed hydration free energies of 1123 small drug-like molecules (both neutral and charged). Temperature derivatives were also used to calculate hydration energies and entropies of 74 of these molecules (both neutral and charged) for which experimental data is available. While direct results have rather poor agreement with experiment, we have found that several previously proposed linear hydration free energy correction schemes give good agreement with experiment. These corrections also provide good agreement for hydration energies and entropies though simple extensions are required in some cases.
隐式溶剂模型提供了一种有吸引力的方法，可用于估计溶剂环境对小分子或大分子溶质性质的影响，而无需进行显式模拟带来的复杂计算。一种常见的准确性测试是计算各种小分子从气相转移到液相的自由能，因为其中许多值已被测量。对这些值的温度依赖性（即溶剂化焓和熵）进行研究，可以为隐式溶剂模型的性能提供更多见解。在此，我们展示了如何使用3D-RISM积分方程方法计算水合自由能的温度导数。我们计算了1123个类药物小分子（包括中性和带电分子）的水合自由能。还使用温度导数计算了其中74个分子（包括中性和带电分子）的水合能和熵，这些分子有可用的实验数据。虽然直接结果与实验的一致性相当差，但我们发现，一些先前提出的线性水合自由能校正方案与实验结果吻合良好。通过在某些情况下进行简单扩展，这些校正对于水合能和熵也能提供良好的一致性。
