The Problem of Protein Denaturation

Proteins are known to undergo a process of denaturation upon heating or changing the solvent condition. By denaturation we refer to the loss of the specific function—say, enzymatic activity—of the protein. It is also known that this process involves the breakdown of the specific three-dimensional structure of the protein, which is essential for its function, i.e., a transition from a well-defined folded form (F) into a random or partially random unfolded form (U). We denote this process schematically as 

There are many experimental means by which one can follow the transition from F to U as a function of temperature, pressure, pH, addition of solutes, etc. For instance, one may follow the absorption spectra of a specific group in the protein as a function of temperature. As the protein unfolds, the environment of that specific group changes and this change will be revealed in the absorption spectra. We can account for the general features of this curve by using a simple, two-state-model approach, due to Schellman.  

Let Pf and pu be the densities of the F and the U forms, respectively. At equilibrium we have the equality of the chemical potentials 

Note that Xf is the fraction of the protein in the F form, not the mole fraction of F in the solution. 

In terms of fixed values of A// , A5 , and C, we can write the explicit dependence of xf on temperature as 

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