Faster Sampling in Molecular Dynamics Simulations with TIP3P-F Water.

Abstract

The need for short time steps currently limits routine atomistic molecular dynamics (MD) simulations to the microsecond time scale. For long time steps, the numerical integration of the equations of motion becomes unstable, resulting in catastrophic crashes. Here, we combine mass repartitioning and rescaling to construct a water model that increases the sampling efficiency in biomolecular simulations without compromising integration stability and with preserved structural and thermodynamic properties. The resulting "fast water" is then used with a time step as before in combination with standard force fields. The reduced water viscosity and faster diffusion result in proportionally faster sampling of the larger-scale motions in the conformation space of both solute and solvent. We illustrate this approach by developing TIP3P-F based on the popular TIP3P model of water. A roughly 2-fold boost in the sampling efficiency at minimal cost in accuracy is substantial and helps lower the energy impact of large-scale MD simulations. The approach is general and can readily be applied to other water models and different types of solvents.