A fast-slow method to treat solute dynamics in explicit solvent.

Aiming to reduce the computational cost in the current explicit solvent molecular dynamics (MD) simulation, this paper proposes a fast-slow method for the fast MD simulation of biomolecules in explicit solvent. This fast-slow method divides the entire system into two parts: a core layer (typically solute or biomolecule) and a peripheral layer (typically solvent molecules). The core layer is treated using standard MD method but the peripheral layer is treated by a slower dynamics method to reduce the computational cost. We compared four different simulation models in testing calculations for several small proteins. These include gas-phase, implicit solvent, fast-slow explicit solvent and standard explicit solvent MD simulations. Our study shows that gas-phase and implicit solvent models do not provide a realistic solvent environment and fail to correctly produce reliable dynamic structures of proteins. On the other hand, the fast-slow method can essentially reproduce the same solvent effect as the standard explicit solvent model while gaining an order of magnitude in efficiency. This fast-slow method thus provides an efficient approach for accelerating the MD simulation of biomolecules in explicit solvent.