AnfinsenDogma

Anfinsen's dogma, also known as the thermodynamic hypothesis of protein folding, is a principle in biochemistry stating that the native three-dimensional structure of a protein is determined by its amino acid sequence and that, under physiological conditions, the information required to fold into this structure is contained in the sequence alone. The native state is considered the thermodynamically favored conformation, i.e., the global free-energy minimum, assuming a suitable cellular environment.

The concept emerged from Christian B. Anfinsen's experiments in the 1950s and 1960s, which culminated in the demonstration that ribonuclease could regain activity after denaturation. Anfinsen and colleagues argued that the information necessary for folding resides in the primary sequence, and that the correct structure could be obtained if the protein is allowed to reach its native state without interference. Anfinsen was awarded the Nobel Prize in Chemistry in 1972 for his ribonuclease work, a key foundation for the dogma.

In his classic ribonuclease A experiments, the enzyme was denatured with urea and beta-mercaptoethanol, which reduced disulfide bonds. Upon removal of these denaturants, the protein refolded into its active native conformation, supporting the idea that sequence alone encodes folding information.

Modern understanding acknowledges that while the amino acid sequence contains the information required for folding, the cellular context—including molecular chaperones, co-translational folding, and post-translational modifications—influences folding trajectories and efficiency. Thus, the dogma is a foundational, but simplified, view; exceptions and complexities exist in vivo.