With most of these simulations, the cysteine and aspartate from the DCH zinc site move between the two zincs, causing the H3 zinc site to become octahedral with three histidines, crystal water, cysteine, and aspartic acid. The ligand becomes bidentately coordinated to zinc and the coordination changes from tetrahedral to square pyramidal. Figure Comparing the coordination geometries of the outlier transformations to those lying within the gray region in Fig. , we see that in the results that correlate better with experiments (i.e. within the gray region), the zinc coordination is much more conserved. In these simulations, the H3 site still becomes octahedral, with two additional water molecules coordinating to the zinc, but the DCH site remains tetrahedral with the ligand sitting bidentate to zinc. This suggests that the RBFE prediction is less sensitive to the changes in the H3 site as long as the DCH site remains tetrahedral. Furthermore, coordination changes are not unexpected with the restraint approach, as it does not capture the polarization effects of metal coordination. (non-normal), we carried out the Mann-Whitney U statistic between the UAFF and restraint models to determine if the differences in these statistics are statistically significant. Table in the SI shows the Mann-Whitney U test statistic and its corresponding p-value for each statistic. As all p-values are below the chosen significance level of α = 0.05, we reject the null hypothesis that the two distributions are equal and state that the difference is statistically significant.