A Minimal Protein Folding Model To Measure Hydrophobic and CH–π Effects on Interactions between Nonpolar Surfaces in Water

In the balance: A synthetic molecule that exhibits two-state folding behavior in water is described. Quantitative experiments reveal that the microscopic hydrophobic effect is similar in magnitude to the CH–π interaction. These forces may therefore be equally important in the folding of aromatic-rich regions of proteins. The method allows a new approach to the direct measurement of excess surface energy associated with nonpolar surfaces.