Molecular basis of osmolyte effects on protein and metabolites.

Osmolytes can have strong effects on biochemical reactions, such as protein folding or protein-ligand interaction. These effects are mediated through solvation-the nonspecific interaction between the solution components. Therefore, understanding the impact of osmolytes on cellular biochemistry requires an understanding of the underlying solvation processes. This chapter discusses the thermodynamic effects of osmolytes on proteins and small organic molecules in terms of the solvation of these molecules, as derived from Kirkwood-Buff theory. This approach allows experimental determination of solvation properties from thermodynamic data. Knowledge of solvation at this level provides insight into the observed behavior of proteins and small molecules in osmolyte solution on a microscopic level. As examples, we provide solvation effects on protein folding, ligand binding, and osmolyte thermodynamics.