A Multiple-Time-Step Molecular Dynamics Algorithm for Macromolecules

We present a computationally efficient molecular dynamics algorithm designed to take advantage of the inherent separation of time scales in biomolecular systems. The algorithm is essentially a generalization of the previously introduced reversible reference system propagation algorithm (r-RESPA) which employs a Trotter factorization of the Liouville propagator to generate numerical integration schemes for molecular dynamics applications. The method is compared with thevelocity Verlet integration algorithm in a molecular dynamics (MD) simulation of the protein crambin in vucuo. The multiple-time-step algorithm is shown to be able to take a much larger time step for a comparable level of accuracy than that of the standard method, leading to a 4-5-fold reduction in the CPU time required to calculate the nonbonded forces.