In a similar vein, given the limited sampling, our goal here is not to draw definitive conclusions about the different force fields and water models and recommend one combination over another but to demonstrate how they should be rigorously and thoroughly interrogated. Ideally, new water models, force fields or versions of force fields should demonstrate appreciably improved performance in terms of error distributions, both absolute and relative, centered around x = 0 kcal/mol and x = 100% (perfect predictions), respectively, being taller and narrower than their predecessor or the previous gold standard, rather than merely improving parameters for one group or another or marginally improving R 2 in benchmarking. This does not appear to be the case for GAFF2.11 and 1.81, at least when using TIP3P water (SI Fig. ). However, again, we reserve judgement until sufficient sampling can be attained, and merely suggest how this matter should be interrogated.