Decomposition of Intramolecular Interactions Between Amino-Acids in Globular Proteins-A Consequence for Structural Classes of Proteins and Methods of Their Classification (original) (raw)
An amino-acid in proteins shows two different, yet mutually dependent faces connected through the polymer character of a protein in the final product. They are the amino-acid sidechain and its corresponding backbone part. On the level of the side-chains, we often refer to specific structural arrangements such as hydrophobic cluster motifs, salt-bridge motifs or hydrogen-bond motifs characterizing various parts of a protein and usually assigned to a certain function. The backbone on the other hand offers limited, yet general structural motifs - and random coil patterns. All of these mentioned amino-acid features contribute to the synergy demonstrated observably by protein stability and protein function. Thermal stability is one of the most important features of the structure of a fully folded protein. It is defined as the difference in the Gibbs free energy between its native and denaturated states and as such is a function of temperature and implicitly a function of protein composition and the effect of the environment. Nevertheless, it is necessary to say that for this function we do not know yet the precise and general form which could be applicable for a large set of proteins. There have been many attempts to propose an intuitive, yet productive decomposition of Gibbs free stabilization energy (GFSE) into simple terms. One of the scenarios utilized for such purposes is that the total free energy is the sum of the free energies of various atomic groups and the hydrophobic effect. However, as the free energy is not additive and the fractionation of free energy to independent terms is difficult, this attempt has been quite unsuccessful. The utilization of molecular modeling methodology and tools has opened a more systematic and perhaps more promising approach -the evaluation of the enthalpy term in the equation for Gibbs free energy with reasonable accuracy . The remaining entropy term could be obtained by fitting the corresponding analytical form to the experimental data. There are basically three different enthalpy contributions that we can separate. The first comes from the intramolecular interactions between the atoms of proteins, producing the largest stabilizing enthalpy contribution. The second comes from the interactions between the molecules of a solvent, and finally the third contribution is the result of the interactions between the atoms of the solute (protein) and the solvent.
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