The equilibrated coordinates were then converted to the Drude model in CHARMM and further equilibrated for 500 ps. Position restraint forces were applied to heavy atoms with a force constant of 1000 kJ mol -1 nm 2 . Periodic boundary conditions were applied in all dimensions and pressure was kept at 1 bar via the Monte Carlo Membrane barostat described above. Unbiased production simulations were carried out for both the additive and Drude systems for 500 ns under an NPT ensemble for data collection, saving coordinates every 10 ps. A complete description of Drude conversion and simulation parameters used for all polarizable systems is provided below.