A new nonpolarizable force field for mixtures of urea and water is described. The model was parametrized to reproduce the experimental Kirkwood-Buff integrals between urea-urea, urea-water, and water-water pairs, as defined by the Kirkwood-Buff theory of solution mixtures. It was observed that the integrals were sensitive to the charge distribution used, and that none of the literature charge distributions investigated produced the correct degree of urea association. However, a hybrid charge distribution was found which accurately reproduced the integrals over a range of concentrations. Correspondingly, the solution thermodynamics, including the activity of urea, were well described. In addition, other physical properties (density, diffusion constants, compressibility) were also well reproduced. The model displayed little or no urea self-aggregation, in agreement with the experimental data. The ideal nature of urea mixtures (molar activity scale) appeared to result from a balance between water-water and urea-water interactions, with a smaller urea-urea interaction. Although developed for use with SPC/E water, the new model performed equally well with the SPC and TIP3P water models.

A force field for the simulation of mixtures of sodium chloride and water is described. The model is specifically designed to reproduce the experimentally determined Kirkwood–Buff integrals as a function of salt concentration, ensuring that a good representation of the solution activity is obtained. In addition, the model reproduces many of the known properties of sodium chloride solutions including the density, isothermal compressibility, ion diffusion constants, relative permittivity, and the heat of mixing. The results are also compared to other common sodium chloride force fields.

The effect of cosolvents on biomolecular equilibria has traditionally been rationalized using simple binding models. More recently, a renewed interest in the use of Kirkwood-Buff (KB) theory to analyze solution mixtures has provided new information on the effects of osmolytes and denaturants and their interactions with biomolecules. Here we review the status of KB theory as applied to biological systems. In particular, the existing models of denaturation are analyzed in terms of KB theory, and the use of KB theory to interpret computer simulation data for these systems is discussed.

A force field for the simulation of methanol and aqueous methanol mixtures is presented. The force field was specifically designed to reproduce the experimental Kirkwood-Buff integrals as a function of methanol mole fraction, thereby ensuring a reasonable description of the methanol cosolvent and water solvent activities. Other thermodynamic and physical properties of pure methanol and aqueous methanol solutions, including the density, enthalpy of mixing, translational diffusion constants, compressibility, thermal expansion, and dielectric properties, were also well reproduced.