Efficient Calculation of Excess Free Energy of Pure and Mixed Alcohol Solutions

Abstract The calculation of free energy of pure and mixed solution is important in chemistry and related fields. Existing accurate methods use alchemical approaches which require multiple molecular dynamics simulations for a series of artificial intermediate states and are computationally expensive. Here we present an efficient method to calculate excess free energies (both enthalpy and entropy) of pure and mixed alcohol solutions. The present method calculates both enthalpy and entropy of the solution system directly from a single MD trajectory. We performed free energy calculations for several alcohol solutions using two different force fields for comparison with each other and with experimental results. The method is for general mixed solutions with application to mixed water-methanol and water-ethanol solutions at various degrees of mixtures. The calculated numerical results are generally in good agreement with experimental data.