Free energy measurements by the generalized fluctuation theorems: Theory and numerical study of a model filament

Abstract : We measure the free energy of a model filament, which undergoes structural transitions, as a function of its extension, in silico. We perform Brownian Dynamics (BD) simulations of pulling experiments at various speeds, following a protocol close to experimental ones. The results from the fluctuation theorems are compared with the estimates from Monte Carlo (MC) simulation, where the rugged free energy landscape is produced by the density of states method. The fluctuation theorems (FT) give accurate estimates of the free energy up to moderate pulling speeds. At higher pulling speeds, the work distributions do not efficiently sample the domain of small work and FT slightly overestimates free energy. In order to comprehend the differences, we analyze the work distributions from the BD simulations in the framework of trajectory thermodynamics. The measured work-free energy relation is consistent with the results obtained from the generalized fluctuation theorems that take into account informations (relative entropies). We discuss operational methods to improve the estimates at high pulling speed.