Force probe simulations using a hybrid scheme with virtual sites.

Abstract

Hybrid simulations, in which a part of the system is treated with atomistic resolution and the remainder is represented on a coarse-grained level, allow for fast sampling while using the accuracy of atomistic force fields. We apply a hybrid scheme to study the mechanical unfolding and refolding of a molecular complex using force probe molecular dynamics (FPMD) simulations. The degrees of freedom of the solvent molecules are treated in a coarse-grained manner while atomistic resolution is retained for the solute. The coupling between the solvent and the solute is provided using virtual sites. We test two different common coarse-graining procedures, the iterative Boltzmann inversion method and the force matching procedure, and find that both methodologies give similar results. The results of the FPMD simulations are compared to all-atom simulations of the same system and we find that differences between these simulations and the ones using the hybrid scheme are in a similar range as the differences obtained when using different atomistic force fields. Thus, a hybrid scheme yields qualitatively correct results in the strong non-equilibrium situation the system is experiencing in FPMD simulations.