The effect of pH on thermal stability of globular proteins : a critical insigh

In this study we try to re-analyze the pH dependence of thermal stability of small globular proteins. From the thermodynamic point of view a long series of calorimetric and spectroscopic investigations has shown that the decreased stability in very acidic conditions can be ascribed to entropic effects. The same conclusion is reached, from a microscopic point of view, by assuming that a binding of protons on equal and noninteracting sites takes place as a consequence of unfolding process. By linking the conformational unfolding equilibrium to the proton binding equilibrium, a model is developed that is able to describe the dependence on the pH of the thermal denaturation processes of small globular proteins. The application of the model to hen lysozyme and T4 lysozyme correctly accounts for the experimental results.