Thermodynamic hypothesis

Anfinsen’s dogma (lecture)
American mathematician Stephen Smale (Ѻ) at the Institute for Science and Technology, Australia, lecturing on Anfinsen’s dogma, aka the thermodynamic hypothesis.
In protein thermodynamics, thermodynamic hypothesis, or “Anfinsen’s dogma”, states that the three-dimensional structure of a native protein in its normal physiological milieu (solvent, pH, ionic strength, presence of other components such as metal ions or prosthetic groups, temperature, etc.) is the one in which the Gibbs free energy of the whole system is lowest; that is, that the native conformation is determined by the totality of interatomic interactions and hence by the amino acid sequence, in a given environment. [1] Said another way, a protein’s native structure is determined solely by the protein’s amino acid sequence components and the environmental conditions in which the folding occurs, such that the native structure is a unique, stable, and kinetically accessible state corresponding to a Gibbs free energy minimum.

History
The hypothesis was put forward by American biochemist Christian Anfinsen in the 1950s who reasoned that the information determining the tertiary structure of a protein resides in the chemistry of its amino acid sequence. Investigations on reversible denaturation of several proteins served to verify this proposal experimentally. The paper presenting his theory seems to be the 1973 article “Principles that Govern the Folding of Protein Chains”, in which he showed that under the proper solvent conditions, amino acid sequence fold spontaneously into functional three-dimensional protein structures, and that the process was governed thermodynamically. [2] Anfinsen won half the 1972 Nobel Prize in chemistry for this work on “ribonuclease, especially concerning the connection between the amino acid sequence and the biologically active conformation.” [3]

References
1. Anfinsen, C.B. (1973). “Principles that Govern the Folding of Protein Chains” (abstract) Science, 181: 223-30.
2. Larson, Scott A. and Hilser, Vincent J. (2004). “Analysis of the ‘Thermodynamic Information Content’ of a Homo sapiens Structural Database reveals Hierarchical Thermodynamic Organization”, Protein Science, 13: 1787-1801.
3. Anfinsen, Christian B. (1972). “Studies on the Principles that Govern the Folding of Protein Chains.” Nobel Lecture, Dec. 11.

External links
Anfinsen’s dogma – Wikipedia.

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