Elastic barrier dynamical freezing in free energy calculations: A way to speed up nonequilibrium molecular dynamics simulations by orders of magnitude

An important issue concerning computer simulations addressed to free energy estimates via nonequilibrium work theorems, such as the Jarzynski equality [Phys. Rev. Lett. 1997, 78, 2690], is the computational effort required to achieve results with acceptable accuracy. In this respect, the dynamical freezing approach [Phys. Rev. E 2009, 80, 041124] has been shown to improve the efficiency of this kind of simulations, by blocking the dynamics of particles located outside an established mobility region. In this report, we show that dynamical freezing produces a systematic spurious decrease of the particle density inside the mobility region. As a consequence, the requirements to apply nonequilibrium work theorems are only approximately met. Starting from these considerations, we have developed a simulation scheme, called "elastic barrier dynamical freezing", according to which a stiff potential-energy barrier is enforced at the boundaries of the mobility region, preventing the particles from leaving this region of space during the nonequilibrium trajectories. The method, tested on the calculation of the distance-dependent free energy of a dimer immersed into a Lennard-Jones fluid, provides an accuracy comparable to the conventional steered molecular dynamics, with a computational speedup exceeding a few orders of magnitude.