| Free energy perturbation simulation has been a powerful and successful method for computation of the free energy change upon solvation. First, the basicities of amines are investigated using ab initio quantum calculations and molecular dynamics free energy perturbation calculations. The peculiar tendency of amine basicity is the result of slight deviation from the linear relationship between methylation and the associated free energy changes in both the hydration of protonated amines and the protonation of amines in gas phase that are large and in opposite direction to each other. The desolvation free energy of amines, though most difficult to reproduce, contributes little to the overall basicity. Next, we propose methods to decompose the free energy computation into its energy and entropy components. With our decomposition scheme, we are able to relate macroscopic thermodynamic quantities more directly to the microscopic structure change upon solvation than with free energy alone, thus providing more detailed comprehension of solvation processes. Placing a focus upon hydration of small organic molecules, particularly alkanes and amines, we investigate the nature of hydrophobic and polar hydration mechanisms. The decomposition scheme also allows us to validate the enthalpy entropy compensation that are often believed to be universal. With our computational studies and sorting of experimental data, it is shown that the compensation is not universal, though it is widely observed. Solvation processes occur beyond normal conditions. Chloride ion solvation in supercritical water is investigated with water polarizability explicitly. Comparisons are made between the TIP4P fluctuating charge and standard TIP4P models. The chloride ion hydration number decreases with supercritical water density in a similar way for the fluctuating charge and fixed charge water models. The orientational structure of the water near the ion is enhanced for the polarizable model relative to the standard TIP4P results. The diffusion coefficients for the two models also exhibit a similar density dependence except at the lowest density for which the chloride ion diffusion in polarizable water is significantly larger than in non-polarizable water. |
