Integrating Multiple Time Step Method and Implicit Solvent Model for Molecular Dynamics Simulations of Proteins

In this work, we integrated the multiple time step (MTS) approach with the generalized Born (GB) implicit solvent model for molecular dynamics (MD) simulations of protein systems. The total forces for the protein systems can be decomposed into two terms: slow forces corresponding to the solvation energy term in GB, and fast forces relevant to potential energy in vacuum. An integrator with the reversible Trotter decomposition scheme, in which the former is determined each N steps and used for the next N-1 steps, was performed on MD simulations of four protein systems with different secondary structures. It was observed that the results using MTS until N = 4 are in good agreement with the reference simulations in which each force term is updated at each step. We further compared the performances of four widely-used GB models: STILL, HCT, OBC and GRYCUK, in the framework of GB-MTS. The influence of different Born radius calculation methods is usually more significant than that of the MTS approach.