Marginal stability of proteins

Proteins are therefore dynamic, flexible objects whose physical and chemical properties are dominated, not only by their conformation, but also by the continual changes in conformation which are a consequence of their microscopic size22). The marginal stability of most protein conformations suggests that processes at one point in the protein might well have an effect on a portion of the molecule far removed. 

The differential solubilities exhibited by biomolecules thus should be appreciated as one of the most important aspects of the effects of water on living systems. Differential solubility is a critical principle in much of biochemical evolution, and it is a principle that is manifested in a number of contexts of adaptation to the environment. This is seen particularly clearly in the evolution of proteins in the face of different chemical and physical conditions. The amino acids selected to construct a particular protein reflect a finely tuned process that results in the generation of an appropriate three-dimensional structure and a correct balance between structural stability and flexibility—a balance termed marginal stability—that is essential for protein function. The marginal stability of the protein will be seen to be the consequence of complementary adaptations in the protein... 

Wang L, Colon W (2005) Urea-induced denaturation of apolipoprotein serum amyloid A reveals marginal stability of hexamer. Protein Sci 14 1811—1817... 

Polymers designed with this technique have a number of important aspects in common with proteins. First of all, the transition from a liquid-like globule into a frozen state occurs as a first order phase transition. Further, the frozen state itself has an essential stability margin, which is determined by the design parameters. As in real proteins, neither a large variation of temperature or other environmental conditions, nor a mutational substitution of several monomers leads to any change in basic state conformation. In this respect the ability of sequence design to capture certain essential characteristics of proteins seems quite plausible. 

In the context of protein structure, the term stability can be defined as the tendency to maintain a native conformation. Native proteins are only marginally stable the AG separating the folded and unfolded states in typical proteins under physiological conditions is in the range of only 20 to 65 kJ/mol. A given polypeptide chain... 

Also, Schellman s work is pertinent (1809). From studies on heats of dilution of urea in water he concludes that the N—H 0=C bond has an enthalpy of 1.5 kcal/mole in aqueous solution, and he carries this value over to proteins and polypeptides. Among these complicated materials he is forced to approximate—but he deduces relations which show the stability of helices and sheets in terms of H bond enthalpy and configurational entropy. From this he draws the important conclusion that H bonds, taken by themselves, give a marginal stability to ordered structures which may be enhanced or disrupted by the interactions of the side chains. Schellman ends his papers with a discussion of experimental tests needed to eliminate some of the assumptions in his theoretical analysis. 

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