Free energy of denaturation

Why denaturants such as urea and GdmCl cause proteins to denature may be considered empirically. Those denaturants solubilize all the constituent parts of a protein, from its polypeptide backbone to its hydrophobic side chains. To a first approximation, the free energy of transfer of the side chains and polypeptide backbone from water to solutions of denaturant is linearly proportional to the concentration of denaturant.7,8 Because the denatured state is more exposed to solvent than the native state, the denatured state is preferentially stabilized by denaturant. Thus, the free energy of denaturation at any particular concentration of denaturant is given by... 

Figure 16.13 The free energy of denaturation AfjG as a function of temperature for a number of proteins Lys = lysozyme Rna = ribonuclease A Ct = a-chymotrypsin Cyt = cytochrome c Mb = metmyoglobin Tr = Trypsin and PTI2 = the dimer of pancreatic trypsin inhibitor. Reprinted with permission from P. L. Privalov, Stability of Proteins — Small Globular Proteins, Adv. Prot. Chem., 33, 167 (1979).

Figure 12.8. Simulation of decreases in the standard state free energy of denaturation (AGq) as a function of increases in temperature. denotes the denaturation midpoint temperature.

Kato and Yutani [28] correlated the surface activity of six mutants of tryptophan synthase a-subimits with their stability, as measured by their free energy of denaturation in water (AG ater)- 0 1 measure of surface activity was given by the air-liquid siuface tension of a mutant solution. These results are in line with the previous examples and demonstiate the importance of conformational stability in predicting the difference in the adsorptive behavior among proteins. Incidentally, it serves as another example suggesting that the surface tension of protein, ypy, is related to its intrinsic conformational stability. 

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