A MULTIPLE-TIME-STEP MOLECULAR-DYNAMICS ALGORITHM FOR MACROMOLECULES

We present a computationally efficient molecular dynamics algorithm de signed 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 alg orithm (r-RESPA) which employs a Trotter factorization of the Liouvill e propagator to generate numerical integration schemes for molecular d ynamics applications. The method is compared with the velocity Verlet integration algorithm in a molecular dynamics (MD) simulation of the p rotein crambin in vacuo. The multiple-time-step algorithm is shown to be able to take a much larger time step for a comparable level of accu racy than that of the standard method, leading to a 4-5-fold reduction in the CPU time required to calculate the nonbonded forces.