Thermodynamics of protein folding: effects of hydration and electrostatic interactions.
DNA base sequences contain a variety of information, and this information flows from DNA to a protein through the steps of transcription and translation. The one dimensional information given from DNA is the amino acid sequence of the protein. In an organism, a nascent chain synthesized in vivo from the N-terminus according to the information in DNA folds spontaneously to a native conformation under a given environmental condition, i.e., water is the solvent and concentration of salts, pH, temperature, and pressure are appropriate. The polypeptide chain synthesized chemically from the C-terminus also folds to the native conformation, and often exhibits the proper enzymic activity. X-ray crystallography reveals the three dimensional structure of a protein in crystal, indicating that the location of the constituent atoms in the space is specific for that protein, i.e., the information on how to fold is contained in the amino acid sequence. In order to understand the folding, however, other factors such as geometrical information on each amino acid should be taken into account, because a sequence is one dimensional information and a 3D structure is three dimensional. Environmental conditions are also crucial factors in the folding, since a change in conditions can destroy the native structure. The folding and unfolding phenomena are described in terms of thermodynamics when the processes occur reversibly. As experiments show, the stability of a protein conformation can be described by the free energy of folding or unfolding. Folding of a nascent chain to the native conformation, thus, is interpreted as the process towards a minimum of the folding free energy. Thermodynamic quantities of folding or unfolding are expressed as functions of temperature, pressure, and concentration of reagents such as salts, and the quantities are measured as the differences between states, e.g., the N and D states. Since the effects of surrounding media must be included, the phenomenon in aqueous solution at a given condition of pH and salt concentration is divided into the several steps shown in Fig. 12. The chain molecule has two states, N and D, in vacuo; the molecule is then transferred into water, accompanied by the hydration in both states; next, the ionization process produces electrostatic interactions in the molecule; and finally, addition of chemical reagents like denaturants has other effects on the stability.
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Department of Food Sciences, Kyoto Women's University, Japan.
D000818:Animals; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004563:Electrochemistry; D006801:Humans; D046911:Macromolecular Substances; D008433:Mathematics; D010455:Peptides / Q000737:chemistry; D014176:Protein Biosynthesis; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
D046911:Macromolecular Substances; D010455:Peptides; D011506:Proteins; D004247:DNA