Protein structure thermodynamics

A. V. Einkelstein, Proteins structural, thermodynamic and kinetic aspects, in Slow Relaxations arul Nonequilibrium Dynamics (J. L. Barrat and J. Kurchan, eds.) Springer-Verlag, Berlin, 2004, pp. 650-703. 

Christian Anfmsen s experiments demonstrated that proteins can fold reversibly. A corollary result of Anfmsen s work is that the native structures of at least some globular proteins are thermodynamically stable states. But the matter of how a given protein achieves such a stable state is a complex one. Cyrus Levinthal pointed out in 1968 that so many conformations are possible for a typical protein that the protein does not have sufficient time to reach its most stable conformational state by sampling all the possible conformations. This argument, termed Levinthal s paradox, goes as follows consider a protein of 100 amino acids. Assume that there are only two conformational possibilities per amino acid, or = 1.27 X 10 ° possibilities. Allow 10 sec for... 

Coming, P.A. (2002). Thermoeconomics beyond the second law. J. Bioeconom., 4, 57-88 Everett, D.H. (1959). An Introduction to Chemical Thermodynamics. Longmans, London Kinosita, K., Yasuda, R., Noji, H. and Adachi, K. (2000). A rotary molecular motor that can work at near 100% efficiency. Philos. Trans. Act. Royal Soc. London B, 355, 473—489. See also Proc. Biochem. Soc. (2005) Meeting Mechanics of Bioenergetic Membrane Proteins Structures and... 

Privalov, P.L. and N.N. Khechinashvili. 1974. A thermodynamic approach to the problem of stabilization of globular protein structure a calorimetric study. J Mol Biol 86 665-684. 

Cytochrome c and cytochrome c peroxidase (ccp) are physiological partners in the ccp reaction cycle structural, thermodynamic, and kinetic data are available for the protein-protein interaction [69-72]. A model indicates that the cyt c/ccp complex is stabilized by specific salt bridges with the hemes in parallel planes the Fe-Fe distance is 24 A, and the edge-edge distance is 16 A [70]. 

The substantial free energy available in the binding of hemes into natural proteins is frequently harnessed to fold or stabilize the final protein structure as observed in the differences in the apo- (77) and holo-structures (73) of cytochrome 6562 shown in Fig. 2. Although detailed thermodynamic studies of natural heme proteins are beginning... 

Table 3.1). Thus, for a redox reaction to be possible, the difference between the redox potential of the enzyme-cofactor system and that of the substrate must be above zero [3]. The catalytic role of the enzyme protein structure in a redox reaction is often to alter the electronic environment of the cofactor, thereby changing its redox potential and hence making the reaction more thermodynamically feasible. (For further in-depth discussion the reader is referred to the excellent text of Bugg [3].)...

Thermodynamics has in this case to do with the specificity of the protein structure that determines the binding selectivity to one another, for example actin and... 

Belyakova, L.E., Semenova, M.G., Antipova, A.S. (1999). Effect of small molecule surfactants on molecular parameters and thermodynamic properties of legumin in a bulk and at the air-water interface depending on a protein structure in an aqueous medium. Colloids and Surfaces B Biointerfaces, 12, 271-285. 

Formation of protein gel structures can occur under conditions which disrupt the native protein structure provided that the protein concentration, thermodynamic conditions and other conditions are optimal for the formation of the tertiary matrix. The most Important food processing techniques relative to protein gelation Involve divalent cations (calcium) and/or heat treatment. 

Protein structure is stabilized by multiple weak interactions. Hydrophobic interactions are the major contributors to stabilizing the globular form of most soluble proteins hydrogen bonds and ionic interactions are optimized in the specific structures that are thermodynamically most stable. 

Taylor, J. D., Gilbert, P J., Williams, M. A., Pitt, W. R., and Ladbury, J. E. (2007). Identification of novel fragment compounds targeted against the pY pocket of v-Src SH2 by computational and NMR screening and thermodynamic evaluation. Proteins Structure Function and Bioinformatics 67, 981-990. 

Owing to the complexity of protein structures, model compounds have often been employed in estimating thermodynamic parameters for protein unfolding. The utility of these parameters depends on the validity of the choice of a model system, i.e., how well the model system mimics the process of transferring different functional groups from the protein interior into the solvent. In principle, one would like to choose a reference state that is similar energetically to the protein interior. 

Analysis of the dependence of the structural thermodynamics of globular proteins on apolar surface area provides an estimation of the role of various contributions to protein stability. However, as mentioned above, proteins also show convergence temperatures that can yield similar information, given certain assumptions. 

A comparison of thermodynamic data on denaturation of globular proteins with that of fibrillar proteins and melting of phospholipid membranes led to a conclusion that the van der Waals contribution to the stabilization of protein structure is of the same order as that of hydrogen bonds (Priva-lov, 1982 see also Crigbaum and Komoria, 1979a,b). 

Privalov, P.L. (1989). Thermodynamic problems of protein structure. Ann. Rev. Biophys. Chem. 18, 47-69. 

Directed evolution as a tool to probe the basis of protein structure, stability, and function is in its infancy, and many fruitful avenues of research remain to be explored. Studies so far have focused on proteins that unfold irreversibly, making detailed thermodynamic analysis impossible. The application of these methods to reversibly folding proteins could provide a wealth of information on the thermodynamic basis of high temperature stability. A small number of studies on natural thermophilic proteins have identified various thermodynamic strategies for stabilization. Laboratory evolution makes it possible to ask, for example, whether proteins have adopted these different strategies by chance, or whether certain protein architectures favor specific thermodynamic mechanisms. It will also be possible to determine how other selective pressures, such as the requirement for efficient low temperature activity, influence stabilization mechanisms. The combination of directed evolu-... 

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