Anfinsen's dogma

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Anfinsen's dogma (also known as the thermodynamic hypothesis) is a postulate in molecular biology championed by the Nobel prize laureate Christian B. Anfinsen. The dogma states that, at least for small globular proteins, the native structure is determined only by the protein's amino acid sequence. This amounts to say that, at the environmental conditions (temperature, solvent concentration and composition, etc.) at which folding occurs, the native structure is a unique, stable and kinetically accessible minimum of the free energy. The three conditions:

• uniqueness: Requires that the sequence does not have any other configuration with a comparable free energy. Hence the free energy minimum must be unchallenged.
• stability: Small changes in the surrounding environment cannot give rise to changes in the minimum configuration. This can be pictured as a free energy surface that looks rather like a funnel (with the native state in the bottom of it) than like a soup plate; the free energy surface around the native state must be rather steep and high, in order to provide stability.
• kinetical accessibility: Means that the path in the free energy surface from the unfolded to the folded state must be reasonably smooth or in other words that the folding of the chain must not involve highly complex changes in the shape (like knots or other high order conformations).

How the protein reaches this structure is the subject of the field of protein folding, that has a related dogma called Levinthal's paradox. Levinthal's paradox states that the number of possible conformations available to a given protein is astronomically large. Effectively, this makes computational prediction of protein structure by evaluating all possible conformations unfeasible even for relatively small proteins.

Also, some proteins need the assistance of another protein called a chaperone protein to fold properly. It has been suggested that this disproves Anfinsen's dogma. However the chaperones do not appear to affect the final state of the protein, but seems to primarily work by preventing aggregation of several protein molecules before the protein is folded.

References

• Sela M, White FH Jr, Anfinsen CB (1957). "Reductive cleavage of disulfide bridges in ribonuclease". Science. 125 (3250): 691–692. PMID 13421663.CS1 maint: Multiple names: authors list (link)
• White FH (1961). "Regeneration of native secondary and tertiary structures by air oxidation of reduced ribonuclease". J. Biol. Chem. 236: 1353–1360. PMID 13784818.
• Anfinsen CB, Haber E (1961). "Studies on the reduction and re-formation of protein disulfide bonds". J. Biol. Chem. 236: 1361–1363. PMID 13683523.
• Anfinsen CB, Haber E, Sela M, White FH Jr (1961). "The kinetics of formation of native ribonuclease during oxidation of the reduced polypeptide chain". PNAS. 47: 1309–1314. PMID 13683522.CS1 maint: Multiple names: authors list (link)
• Anfinsen CB (1973). "Principles that govern the folding of protein chains". Science. 181 (96): 223–230. PMID 4124164.
• Moore S, Stein WH (1973). "Chemical structures of pancreatic ribonuclease and deoxyribonuclease". Science. 180 (85): 458–464. PMID 4573392.