Application of a multiple time step algorithm to biomolecular systems

Herein we describe the implementation of the multiple time step method, in conjunction with a reversible integrator and the Nose-Hoover chain method f or temperature and pressure control, into ROAR 1.0. We have extensively tes ted the MTS method on three systems: an antifreeze peptide in water. the or ganic solvent dimethylformamide (DME), and a dimyristoylphosphatidylcholine (DMPC)-based lipid bilayer. From these test simulations, we observe that t he MTS method was capable of producing stable trajectories even when a long time step (e.g., 8 fs) is used, while the SHAKE method was unable to do so . The SHAKE method also disturbs the bond vibrational motion while MTS algo rithm does not when the time step was smaller than 5 fs. We also observe th at we can conservatively obtain a 2.5-fold speed-up using the MTS method ov er a SHAKE simulation using a I fs time step. Overall, the MTS method gives a solid speed-up over the traditional SHAKE method, while simultaneously g iving much more stable trajectories.