We have calculated relative binding affinities for eight tetrafluorophenyl-triazole-thiogalactoside inhibitors of galectin-3 with the alchemical free-energy perturbation approach. We obtain a mean absolute deviation from experimental estimates of only 2-3 kJ/mol and a correlation coefficient (R2) of 0.5-0.8 for seven relative affinities spanning a range of up to 11 kJ/mol. We also studied the effect of using different methods to calculate the charges of the inhibitor and different sizes of the perturbed group (the atoms that are described by soft-core potentials and are allowed to have differing coordinates). However, the various approaches gave rather similar results and it is not possible to point out one approach as consistently and significantly better than the others. Instead, we suggest that such small and reasonable variations in the computational method can be used to check how stable the calculated results are and to obtain a more accurate estimate of the uncertainty than if performing only one calculation with a single computational setup.

中文翻译：

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通过执行方法中的变化来评估自由能扰动计算的稳定性。

我们已经用炼金术自由能微扰方法计算了八种galectin-3的四氟苯基-三唑-硫代半乳糖苷抑制剂的相对结合亲和力。我们从实验估计值中获得的平均绝对偏差仅为2-3 kJ / mol，七个相对亲和力的相关系数（R2）为0.5-0.8，跨度最大为11 kJ / mol。我们还研究了使用不同方法计算抑制剂电荷和不同大小的扰动基团（通过软核势描述且允许具有不同坐标的原子）的效果。但是，各种方法得出的结果都非常相似，因此不可能指出一种方法始终如一且明显优于其他方法。代替，