Protein folding free energy determination

In 1972, Christian Anfinsen received the Nobei Prize in Chemistry for his principie of thermodynamic determinism, that the amino acid sequence aione determines the three-dimensionai structure. In the normal physiological state, the three-dimensional structure of a protein is the one in which the Gibbs free energy of the whole system is at a minimum. Many protein molecules have segments that are folded into a single-stranded a-helix, which is held together by the hydrogen bonds between coils, called a secondary structure. 

A long chain of amino acids attached end-to-end has many possible ways to fold. The final shape, or conformation, of a folded protein molecule is determined by its unique sequence of amino acids and by the effects of environmental conditions on amino acid side chains. The conformation selected is the one that is most stable because it has the lowest free energy (Bloomfield 1979). This conformation is designated the native state of the protein. 

The structure-based thermodynamic method combines the derived binding free energy model with the formalism which computes probabilities of individual amino acids being folded in native-like conformations and thereby allows to determine structural stability of different protein regions [48-53]. In a single site thermodynamic mutation approach, the cooperativity of in-... 

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