Denaturation entropy, configurational contribution

The denaturational increment of the heat capacity might be described partly by the increase of the extent of configurational freedom of the protein molecule upon denaturation. However, as was shown by Sturte-vant (J977) and Velicelebi and Sturtevant (1979), the contribution of this effect to the observed denaturational increment of the protein heat capacity cannot be large. This conclusion becomes especially evident from the impossibility of using this configurational effect alone to explain the negative values of the enthalpy and entropy of protein denaturation at low temperatures. 

The 5 1 rule may be justified on thermodynamic grounds. Thus, Doig and Williams [12] addressed the inconsistencies in I lory s treatment of the entropic contribution to protein denaturation, calculating AAG for denaturation for a cross-linked protein versus its non-cross-linked counterpart. At physiological temperature of 300 K, they estimated A AG 4.4 kcal/mol. This value is essentially independent of protein length and loop size and best represents the insensitivity of experimental values to loop size-dependent configurational entropies [13]. 

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