Capturing the Polarization Response of Solvated Proteins under Constant Electric Fields in Molecular Dynamics Simulations.

We capture and compare the polarization response of a solvated globular protein ubiquitin to static electric (E-fields) using atomistic molecular dynamics simulations. We collectively follow E-field induced changes, electrical and structural, occurring across multiple trajectories using the magnitude of the protein dipole vector (P p ). E-fields antiparallel to P p induce faster structural changes and more facile protein unfolding relative to parallel fields of the same strength. While weak E-fields (0.1-0.5 V/nm) do not unfold ubiquitin and produce a reversible polarization, strong E-fields (1-2 V/nm) unfold the protein through a pathway wherein the helix:β-strand interactions rupture before those for the β1-β5 clamp. Independent of E-field direction, high E-field induced structural changes are also reversible if the field is switched off before P p exceeds 2 times its equilibrium value. We critically examine the dependence of water properties, protein rotational diffusion and E-field induced protein unfolding pathways on the thermostat/barostat parameters used in our simulations.