Predicting the energetics of osmolyte-induced protein folding/unfolding.

A primary thermodynamic goal in protein biochemistry is to attain predictive understanding of the detailed energetic changes that are responsible for folding/unfolding. Through use of recently determined free energies of side-chain and backbone transfer from water to osmolytes and Tanford's transfer model, we demonstrate that the long-sought goal of predicting solvent-dependent cooperative protein folding/unfolding free-energy changes (m values) can be achieved. Moreover, the approach permits dissection of the folding/unfolding free-energy changes into individual contributions from the peptide backbone and residue side chains.