Water hydrogen motions were constrained using SETTLE and either SHAKE or LINCS for other constraints in AMBER or GROMACS respectively. In all cases, simulation temperature was maintained at 298.15 K though Langevin dynamics with a collision frequency of 2 ps -1 . A simulation pressure of 1 atmosphere was maintained using various barostats. For AMBER simulations, a Monte Carlo barostat was employed with a volume exchange attempt frequency of 100 ps. For GROMACS, the initial equilibration steps used the Berendsen barostat with a time constant of 1 ps, followed by the Parrinello-Rahman barostat with a time constant of 2.0 ps for all follow-on equilibration and production simulations. In all cases, a cut-off of 1 nm was used for short range interactions, and long range electrostatics are handled via PME