Ignoring the results for B1, which seemed to be especially affected by water sampling issues, the remaining simulations with force constants fit to simulation showed generally good agreement (within 1 kcal mol -1 ), demonstrating reasonable reproducibility with this restraints scheme. Averaging B2, B3, B1-P, and B3-P yielded a ∆G o Bound of -6.26 ± 0.72 kcal mol -1 for binding pose A.