pH dependent protein stability: A quantitative approach based on Kramerʹs barrier escape

The folding–unfolding mechanism of a protein in a living cell is the result of its molecular response to various perturbations due to changes in the chemical environment such as pH, ion concentration, ligand binding and many other complex chemical reactions. In this letter, a theoretical scheme based on single molecule force spectroscopy experiments and related theories, has been followed to capture the effect of the change of pH for a slow protonation-coupled folding–unfolding process, and the free energy landscape has been quantified in terms of protonation numbers, barrier height and pH, following Kramerʹs barrier crossing formalism.