Faster Sampling\nin Molecular Dynamics Simulations\nwith TIP3P‑F Water

The need for short time steps currently limits routine\natomistic\nmolecular dynamics (MD) simulations to the microsecond time scale.\nFor long time steps, the numerical integration of the equations of\nmotion becomes unstable, resulting in catastrophic crashes. Here,\nwe combine mass repartitioning and rescaling to construct a water\nmodel that increases the sampling efficiency in biomolecular simulations\nwithout compromising integration stability and with preserved structural\nand thermodynamic properties. The resulting “fast water”\nis then used with a time step as before in combination with standard\nforce fields. The reduced water viscosity and faster diffusion result\nin proportionally faster sampling of the larger-scale motions in the\nconformation space of both solute and solvent. We illustrate this\napproach by developing TIP3P-F based on the popular TIP3P model of\nwater. A roughly 2-fold boost in the sampling efficiency at minimal\ncost in accuracy is substantial and helps lower the energy impact\nof large-scale MD simulations. The approach is general and can readily\nbe applied to other water models and different types of solvents.