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.

纯溶液和混合溶液的自由能的计算在化学及相关领域很重要。现有的精确方法使用炼金术方法，该炼金术方法需要对一系列人工中间态进行多个分子动力学模拟，并且计算量大。在这里，我们提出了一种有效的方法来计算纯和混合酒精溶液的过量自由能（焓和熵）。本方法直接从单个MD轨迹计算溶液系统的焓和熵。我们使用两个不同的力场对几种酒精溶液进行了自由能计算，以相互比较并得出实验结果。该方法适用于一般混合溶液，并以不同程度的混合物应用于水-甲醇和水-乙醇混合溶液。