Our results are therefore broadly consistent with the electrostatic mechanism proposed by Camilloni and coworkers, but may not have captured all catalytically-relevant CypA motions too, as the magnitude of the overall field contribution is small. The limitations of the short simulations performed here, notwithstanding the fact that the AMOEBA 2013 protein force field has not been as widely tested and validated as either of the two additive models investigated, mean that we cannot draw unambiguous conclusions regarding the CypA mechanism. Recent detailed investigations of CypA dynamics have required both innovative biophysical techniques, and lengthy advanced sampling methodologies for simulations, and the use of polarizable force fields does not negate this necessity for adequate sampling. However, the accuracy of AMOEBA fields compared to DFT suggests that polarizable simulations provide a promising avenue to better explore the electrostatic contributions to mechanism across members of the cyclophilin family, in a computationally efficient way.