Protein folding is the process by which a polypeptide chain acquires an organized spatial arrangement. The interactions of its amino acid residues with one another and the surroundings favor some arrangements over others. Protein folding can bring chemically useful groups together at an active site without changing their order along the protein backbone. Its importance is practical: knowing a sequence alone does not tell us whether a sample has the structure needed for function. See Cooper: acquiring functional protein structure.
The ribonuclease A refolding experiment showed that an isolated protein could recover its native properties without a pre-existing folded template under suitable laboratory conditions. Anfinsen interpreted this through a thermodynamic hypothesis: the native arrangement minimizes the whole system's Gibbs free energy in the appropriate environment. His Nobel lecture was delivered on 11 December 1972 and published in Science in 1973. The specified environment is part of the claim, not a disposable qualification. See Anfinsen, Principles that Govern the Folding of Protein Chains, Science 181, 223–230 (1973): Nobel lecture, especially p. 223.
This does not imply that every protein rapidly folds unaided. Molecular chaperones can assist protein folding and reduce protein aggregation; required partners, surroundings and time still matter. Goloubinoff and colleagues' 1989 reconstitution experiments demonstrated assistance from two molecular chaperones and ATP in recovering an active enzyme from unfolded chains. This is experimental evidence that assistance can matter even when the chains already have their specified sequences. See Goloubinoff, Christeller, Gatenby and Lorimer, 1989: chaperone-assisted reconstitution of an active enzyme.
