Folding of Protein Chains

The telegram that I received from the Swedish Royal Academy of Sciences specifically cites ". . . studies on ribonuclease, in particular the relationship between the amino acid sequence and the biologically active conformation. . . . The work that my colleagues and I have carried out on the nature of the process that controls the folding of polypeptide chains into the unique three-dimensional structures of proteins was, indeed, strongly influenced by observations on the ribonuclease molecule. Many others, including Anson and Mirsky (1) in the 1930's and Lumry and Eyring (2) in the 1950's, had observed and discussed the reversibilizy of denaturation of proteins. However, the true elegance of this consequence of natural selection was dramatized by the ribonuclease work, since the refolding of this molecule, after full denaturation by reductive cleavage of its four disulfide bonds (Fig. 1), required that only 1 of the 105 possible pairings of