The presence of large, orientationally polarized electric fields arising from specific protein environments is proposed to play a crucial role in numerous biomolecular interactions and enzymatic processes. Estimation of these fields experimentally, for example through vibrational Stark spectroscopy, remains a complex process limited by the requirement for site-specific labeling or binding of a calibrated probe functional group. Simulation techniques are hence perfectly placed to complement experimental measurements, either through calibration and validation of observations, or through further investigation and rationalization of field strengths in systems unamenable to experimental probes, e.g. an enzyme active site. The AMOEBA polarizable force field moves beyond a pairwise additive model of electrostatics by incorporating permanent multipoles (up to quadrupoles) and induced dipoles at each atomic site. The induction of atomic dipoles at every step means that the electric field at each atomic site can be easily extracted from the model. Recently, Fried and coworkers1 showed that the AMOEBA polarizable model improves the representation of environmental electric fields over a pairwise additive model in a number of uniform liquid solutions. Here we evaluate the performance of AMOEBA in representing electric fields in a variety of protein environments, including the active site of the peptidyl-prolyl cis-trans isomerase Cyclophilin A. We use GPU-enhanced simulations to achieve simulation timescales more comparable with those of traditional fixed point charge models. We compare our results with AMOEBA, DFT and fixed charge models, with reference to exploring their potential for further rationalizing biomolecular processes in highly specific electrostatic environments. (1) Fried, S. D.; Wang, L.-P.; Boxer, S. G.; Ren, P.; Pande, V. S. Calculations of the Electric Fields in Liquid Solutions. J. Phys. Chem. B, 2013, 117 (50), 16236–16248

Electric fields in biomolecular systems using the AMOEBA polarizable force field

251st National Meeting (2016)

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