Promisingly, however, studies of enzyme activity and mechanism with polarizable force fields have already begun to allow quantitative insights into electrostatically-driven biological mechanisms that additive force fields appear unable to provide. The results we present from simulations of CypA cannot unambiguously determine a reaction mechanism, nor were they intended to. They are supportive of, but not limited to, an electrostatic role for R55, consistent with what is known for CypA. However the fact that AMOEBA can determine electric fields in CypA with almost DFT-level accuracy indicates that, with suitably equilibrated structural ensembles, provided for example by high-performance software implementations, AMOEBA could be used to accurately probe the ground-state dynamics and electric fields of the wider cyclophilin family within single simulations, and at substantially lower computational cost than is currently required for QM/MM or QM post-processing approaches.