Extending molecular dynamics time scales with milestoning: Example of complex kinetics in a solvated peptide

Abstract

A recently introduced computational algorithm to extend time scales of atomically detailed simulations is illustrated. The algorithm, milestoning, is based on partitioning the dynamics to a sequence of trajectories between "milestones" and constructing a non-Markovian model for the motion along a reaction coordinate. The kinetics of a conformational transition in a blocked alanine is computed and shown to be accurate, more efficient than straightforward molecular dynamics by a factor of about 9, and nonexponential. A general scaling argument predicts a linear speedup with the number of milestones for diffusive processes and an exponential speedup for transitions over barriers. The algorithm is also trivial to parallelize. As a side result, milestoning also produces the free energy profile along the reaction coordinate and is able to describe nonequilibrium motions along one (or a few) degrees of freedom.