Refinement, validation, and application of a charge equilibration force field for simulations of phospholipid bilayers

We present a polarizable force field based on the CHEQ formalism for MD simulations of phospholipid bilayers. This model addresses deficiencies in the dihedral, electrostatic, and LJ parameters of the force field. These parameters were refined using ab initio (conformational energy, polarizability) and experimental (polarizability, density, vaporization enthalpy) data for model compounds chosen to represent different regions of a lipid molecule. We discuss validation of the refined force field by applying it to simulations of a series of liquid alkanes (the model compound for the lipid tails); the computed properties show improved agreement with experiment. Finally, we apply the revised CHEQ force field to simulations of a fully hydrated DMPC bilayer. Computed component density profiles and deuterium order parameters are consistent with previous simulations and with experiment. The CHEQ model predicts greater water penetration into the bilayer interior; this is accounted for in part by the shift in the water dipole moment from 2.6 D in the bulk to 1.9 D in the center. The CHEQ model does not provide an improved prediction of the bilayer dipole potential; however, it does more accurately predict the monolayer dipole potential for DPPC, a less ambiguously defined property. Overall these results demonstrate the importance of accounting for the effects of polarization in molecular simulations of biomolecular systems such as lipid bilayers.