Accurate solvation free energy ΔGsolv predictions require well parametrized force fields. In order to refit Lennard-Jones (LJ) parameters for improved ΔGsolv predictions for a variety of compound classes and chemical environments, a large number of ΔGsolv calculations is required. As the calculation of ΔGsolv is computational expensive, there is need for efficient but precise calculation methods. In this work, we focus on the computation of non-aqueous solvation free energies. We compare ΔGsolv results from highly precise reference simulations for transferring a solute from the vacuum into a condensed phase and results obtained from a thermodynamic cycle implementation. As test systems, we alter LJ parameters ε and σ of widely used GAFF atom types ca, cl, n1, oh and os in various solute/solvent combinations. We examine the degree of configurational space overlap and find an impact by hydrogen bonds and the solvent accessible surface area. We conclude that the application of a thermodynamic cycle for the parametrization of force fields targeting ΔGsolv is useful if the adaptation of LJ parameters is limited to atom types in the solute or if only ε is changed.

中文翻译：

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热力学循环方法对以非水溶剂化自由能为目标的力场参数化的适用性。

准确的溶剂化自由能ΔGsolv预测需要参数化的力场。为了重新调整Lennard-Jones（LJ）参数以改善各种化合物类别和化学环境的ΔGsolv预测，需要进行大量的ΔGsolv计算。由于ΔGsolv的计算在计算上是昂贵的，因此需要有效但精确的计算方法。在这项工作中，我们专注于非水溶剂化自由能的计算。我们比较了用于将溶质从真空转移到冷凝相的高精度参考模拟得到的ΔGsolv结果，以及从热力学循环实现中得到的结果。作为测试系统，我们以各种溶质/溶剂组合更改了广泛使用的GAFF原子类型ca，cl，n1，oh和os的LJ参数ε和σ。我们检查了结构空间重叠的程度，并发现了氢键和溶剂可及表面积的影响。我们得出结论，如果将LJ参数的调整限制为溶质中的原子类型，或者仅更改ε，则将热力学循环应用于以ΔGsolv为目标的力场的参数化将很有用。