Single molecule pulling with large time steps.
Recently, we presented a generalization of the Jarzynski nonequilibrium 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 time steps 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 1-3fs .
Faculty of Physics and Center for Computational Materials Science, University of Vienna, Boltzmanngasse 5, 1090 Vienna, Austria.
Harald
H
Oberhofer
Christoph
C
Dellago
Stefan
S
Boresch