Accuracy of free-energy perturbation calculations in molecular simulation. II. Heuristics

A formalism was developed that provides powerful tools to investigate the inaccuracy problem in FEP calculations. The resulting formalism works together with the simulation length, M, as a group quantity, M exp(ΔS/k), in determining the inaccuracy of free-energy difference. It was revealed that M exp(ΔS/k) well characterizes the common behavior of inaccuracy, and can be used as a good indicator for identifying the accuracy level of the FEP calculation.