In the current work we report on our participation in the SAMPL7 challenge calculating absolute free energies of the host–guest systems, where 2 guest molecules were probed against 9 hosts-cyclodextrin and its derivatives. Our submission was based on the non-equilibrium free energy calculation protocol utilizing an averaged consensus result from two force fields (GAFF and CGenFF). The submitted prediction achieved accuracy of \({1.38}\,\hbox {kcal}/\hbox {mol}\) in terms of the unsigned error averaged over the whole dataset. Subsequently, we further report on the underlying reasons for discrepancies between our calculations and another submission to the SAMPL7 challenge which employed a similar methodology, but disparate ligand and water force fields. As a result we have uncovered a number of issues in the dihedral parameter definition of the GAFF 2 force field. In addition, we identified particular cases in the molecular topologies where different software packages had a different interpretation of the same force field. This latter observation might be of particular relevance for systematic comparisons of molecular simulation software packages. The aforementioned factors have an influence on the final free energy estimates and need to be considered when performing alchemical calculations.

在目前的工作中，我们报告了我们参与计算主客体系统绝对自由能的 SAMPL7 挑战，其中 2 个客体分子针对 9 个主体 - 环糊精及其衍生物进行了探测。我们的提交基于非平衡自由能计算协议，该协议利用来自两个力场（GAFF 和 CGenFF）的平均共识结果。提交的预测达到了\({1.38}\,\hbox {kcal}/\hbox {mol}\)就整个数据集的平均无符号误差而言。随后，我们进一步报告了我们的计算与另一份提交给 SAMPL7 挑战的结果之间存在差异的根本原因，该挑战采用了类似的方法，但配体和水力场不同。因此，我们在 GAFF 2 力场的二面角参数定义中发现了许多问题。此外，我们确定了分子拓扑结构中的特殊情况，其中不同的软件包对相同的力场有不同的解释。后一种观察可能与分子模拟软件包的系统比较特别相关。上述因素对最终的自由能估计有影响，在进行炼金术计算时需要考虑。