Recent Advances in Polarizable Force Fields for Macromolecules: Microsecond Simulations of Proteins Using the Classical Drude Oscillator Model.

Abstract

In this Perspective, we summarize recent efforts to include the explicit treatment of induced electronic polarization in biomolecular force fields. Methods used to treat polarizability, including the induced dipole, fluctuating charge, and classical Drude oscillator models, are presented, including recent advances in force fields using those methods. This is followed by recent results obtained with the Drude model, including microsecond molecular dynamics (MD) simulations of multiple proteins in explicit solvent. Results show significant variability of backbone and side-chain dipole moments as a function of environment, including significant changes during individual simulations. Dipole moments of water in the vicinity of the proteins reveal small but systematic changes, with the direction of the changes dependent on the environment. Analyses of the full proteins show that the polarizable Drude model leads to larger values of the dielectric constant of the protein interior, especially in the case of hydrophobic regions. These results indicate that the inclusion of explicit electronic polarizability leads to significant differences in the physical forces affecting the structure and dynamics of proteins, which can be investigated in a computationally tractable fashion in the context of the Drude model.