Single molecule pulling with large time steps

Abstract

Recently, we presented a generalisation of the Jarzynski non-equilibrium work theorem for phase space mappings. The formalism shows that one can determine free energy differences from approximate trajectories obtained from molecular dynamics simulations in which very large timesteps are used. In this work we test the method by simulating the force induced unfolding of a deca-alanine helix in vacuum. The excellent agreement between results obtained with a small, conservative time step of 0.5 fs and results obtained with a time step of 3.2 fs (i.e., close to the stability limit) indicates that the large time step approach is practical for such complex biomolecules. We further adapt the method of Hummer and Szabo for the simulation of single-molecule force spectroscopy experiments to the large time step method. While trajectories generated with large steps are approximate and may be unphysical - in the simulations presented here we observe a violation of the equipartition theorem - the computed free energies are exact in principle. In terms of efficiency, the optimum time step for the unfolding simulations lies in the range 1-3 fs.

8 pages, 8 figures

References in corpus (6)

• A nonequilibrium equality for free energy differences
• Equilibrium free energy differences from nonequilibrium measurements: a master equation approach
• Rare events and the convergence of exponentially averaged work values
• Single-ensemble nonequilibrium path-sampling estimates of free energy differences
• A proof of Jarzynski's non-equilibrium work theorem for dynamical systems that conserve the canonical distribution
• Equilibrium free energies from fast-switching trajectories with large time steps

Cited by in corpus (6)

• A characteristic of Bennett's acceptance ratio method
• Using bijective maps to improve free energy estimates
• Hysteresis and nonequilibrium work theorem for DNA unzipping
• Optimum bias for fast-switching free energy calculations
• Measuring the convergence of Monte Carlo free energy calculations
• An efficient time-stepping scheme for ab initio molecular dynamics simulations