FREE-ENERGY SIMULATIONS OF METHANE SOLVATION - A STUDY OF INTEGRAND CONVERGENCE PROPERTIES USING THERMODYNAMIC INTEGRATION

This report presents the results of free energy simulations using thermodynamic integration (TI) to calculate the absolute free energy of solvation of methane. The dependence of the integrand on the form of the scaling of the Hamiltonian and the exten of the "growth" of the methane was studied. When the methane-water potential is scaled by between 0.002 and 0.15, the integrand became very noisy and the individual values had high statistical uncertainties. This region was responsible for the major contribution to the total integral. A value for the Helmholtz free energy of solvation of 1.23 kcal/mol was obtained, in comparison to the experimental value of 2.005 kcal/mol. It is evident that the calculation has not as yet converged.