Using overlap and funnel sampling to obtain accurate free energies from nonequilibrium work measurements

Abstract

Two concepts are presented for accurate nonequilibrium work free-energy measurements, realized both in molecular simulation and experiment. First, the need for an intermediate important to both the reference and the target systems (overlap) is indicated. Second, the use of a soft path from each end point to the intermediate (funnel) is demonstrated. Schemes implementing these concepts dramatically improve efficiency and accuracy of free energy calculations, as shown by calculation of the free energy of ion charging in water, and the free energy change in mutation of an adenosine molecule.