Optimal Estimates of Free Energies from Multistate Nonequilibrium Work Data

We derive the optimal ests. of the free energies of an arbitrary no. of thermodn. states from nonequil. work measurements; the work data are collected from forward and reverse switching processes and obey a fluctuation theorem. The max. likelihood formulation properly reweights all pathways contributing to a free energy difference and is directly applicable to simulations and expts. We demonstrate dramatic gains in efficiency by combining the anal. with parallel tempering simulations for alchem. mutations of model amino acids.