Local chemical potential equalization model for cosolvent effects on biomolecular equilibria

A simple model for describing the effects of cosolvents on biomolecular equilibria in solution is presented. The model is developed using the Kirkwood-Buff theory of solutions and relates changes in the chemical potential of the cosolvent, due to the presence of the solute, to changes in the cosolvent (and water) concentrations in the vicinity of the biomolecule. The model is then used to determine the dependence of changes in the free energy for protein denaturation on cosolvent concentration. The experimentally observed linearity for urea, and small deviation from linear behavior for guanidinium chloride denaturation, are reproduced. In addition, the model is also predicted to provide a good description of the helix-inducing effects of TFE solutions.