Asymmetric bias in free-energy perturbation measurements using two Hamiltonian-based models

The two Hamiltonian-based model systems were developed for analyzing the asymmetric bias in free-energy perturbation (FEP) calculations performed in molecular simulations. were investigated. It was observed that the models exhibited the asymmetry that was seen in the calculations, in which the magnitude of the bias was greater when the calculation was performed in one direction. The two models were formulated as a system of N independent particles, each sampling a space in the presence of a one-body field. It was found that the bias was smaller when sampling was performed on the system having a broader work distribution.