First, the 25 ns MD simulations performed with AMOEBA, without replica-averaged NMR restraints, are unlikely to fully explore the equilibrium ground state dynamics of CypA. Field distributions varied between repeat simulations of all four WT and R55A CypA states (Fig. , Table ), suggesting a lack of convergence of the absolute field strengths. However, in all but one simulation AMOEBA fields, projected perpendicular to the proline ring, were relatively smaller than those of either Amber or Charmm. On average, AMOEBA fields also showed a drop in field strength in the R55A mutant simulations, generally supporting the conclusion that R55 makes significant contributions to the active site field in the ground states. Additionally, the control calculation of AMOEBA field strengths taken from a structural ensemble generated with Amber suggests that the use of AMOEBA for MD does not fundamentally change the distribution of configurations explored, in the context of electric fields.