Ewald summation and multiple time step methods for molecular dynamics simulation of biological molecules

Methods by which to determine conditions for a molecular dynamics (MD) simu lation of biological molecules were investigated. Derivation of the optimal parameters of the Ewald summation was described so as to give same precisi on to the real space, the reciprocal space summations and the van der Waals interaction. Later, the procedure by which to determine the condition of t he multiple time step method by RESPA (REference System Propagator Algorith m; Tuckerman et al., 1992, J. Chem. Phys., 97, 1990) was described as exemp lified by MD simulations of a solvated beta-sheet peptide. The conservation of the total energy in a microcanonical ensemble was measured to investiga te the stability of the simulation conditions. The most feasible combinatio n of the rime steps was: 0.25 fs for bond, angle and torsion interactions; 2 fs for van der Waals interaction and Ewald real-space summation; and 4 fs for Ewald reciprocal-space summation. Though it retained an acceptable acc uracy, this condition accelerated the simulation ten-fold compared to that in which a simple velocity-Verlet method with a time step of 0.25 fs was us ed. The update of the correction term due to excluded neighbors was then in vestigated. Better results were obtained when the correction was updated wi th the real-space than when it was updated with the reciprocal-space summat ion. Finally, an MD simulation as long as 50 ps was performed under the opt imal Ewald and RESPA parameters thus determined. The trajectory showed a go od stability, indicating the feasibility of the parameters. (C) 2000 Elsevi er Science B.V. All rights reserved.