Start induced unfolding

The Hill plots in Figure 5.31 provide remarkable insight into the hydrophobic-induced pKa shifts. Starting in the hydrophobically associated state for Model Protein v, on decreasing acid concentration, that is, raising the pH, the pKa of the first carboxyl to form carboxylate is 7.0. In Figure 5.31 A, this is the pKa for the most tightly bound proton. As more carboxylates form, further ionization becomes easier, and finally the last carboxyl to ionize does so with a pKa of 5.7. Remarkably, the last carboxyl to ionize does so with a pKa shifted 1.7 pH units from that of the unperturbed Glu pKa of about 4. Even in the completely unfolded state there remains an apolar-polar repulsion of 2.4 (= 1.7 X 2.3RT) kcal/mole-Glu. ... 

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