Free energy of TIP4P water and the free energies of hydration of CH4 and Cl- from statistical perturbation theory

Statistical perturbation theory has been applied in Monte Carlo simulations to compute the free energy of TIP4P water and the absolute free energies of hydration of methane and chloride ion. The calculations entailed the mutation of a water molecule and of a chloride ion to methane and the subsequent disappearance of the methane in the presence of 216 TIP4P solvent molecules. The NPT ensemble was used at 25°C and 1 atm, so Gibbs free energies were obtained. The mutations to methane proceeded with high precision, while the removal of the methane yielded an uncertainty of about ±0.3 kcal/mol in ΔG. The accord with experimental results is good in all cases; in particular, the computed free energy of TIP4P water is −6.1±0.3 kcal/mol, while the experimental value is −6.3 kcal/mol. The present results demonstrate the utility of statistical perturbation theory for computing absolute free energies of solution and the quality of the underlying potential functions.