Assessing this physical accuracy by comparison to experiment has substantial difficulties. Biophysical techniques for measuring intramolecular electric fields are technically challenging and may require the introduction of unnatural amino acids to act as vibrational probes. Instead, we evaluate the accuracy of AMOEBA electrostatics by comparison to a fully quantum mechanical representation, calculated using the ONETEP linear-scaling density functional theory (DFT) software. ONETEP is based on a reformulation of DFT which takes advantage of the locality of electronic structure to allow DFT calculations with computational effort that increases linearly with the number of atoms, as compared to conventional DFT approaches where the computational effort increases with the third power. As a result, ONETEP can perform calculations on many thousands of atoms, such as entire proteins in solvent, as we do here. A unique characteristic of ONETEP is that it retains the full near-complete basis set accuracy of conventional DFT by in situ optimisation of Non-orthogonal Generalised Wannier Functions (NGWFs) which are expressed in terms of a periodic sinc (psinc) basis set which is equivalent to plane waves. The ONETEP program has been developed to run on parallel computers, using hybrid MPI-OpenMP parallelism. To test the ability of biomolecular force fields to reproduce the electric fields derived from DFT we first perform ns-length AMOEBA molecular dynamics (MD) simulations of CypA to generate structural ensembles for wild-type (WT) and mutant systems. We then calculate electric fields at the reaction site using AMOEBA, and the widely used Amber ff14SB 2 and Charmm C36m 3 additive protein force fields.