A method of molecular simulation of free energy

A method of molecular simulation of free energy is proposed to sample the Boltzmann exponential functional of molecular interaction energy exp[−u/kT] by the Metropolis Monte Carlo algorithm. To obtain the Helmholtz energy at (N,V,T), the average of the samples in the canonical ensemble is calculated at 2T, 4T, 8T,... . The residual Helmholtz energy of a molecule (ar/kT) is given by the sum of the logarithms of the reciprocals of the averages extended to a high temperature, plus (ar/kT)T→∞. The latter quantity is equal to (ar/kT) of the hard core of the molecule, or zero if the ideal gas state is obtained at high temperature. The method avoids the insertion of a molecule in a fluid, which is difficult at high density, especially for polyatomic molecules.