On the relevance of non-random polypeptide conformations for protein folding.

The possibility that any non-random conformation in reduced bovine pancreatic trypsin inhibitor (BPTI) and ribonuclease A might be significant for folding has been considered, using the experimental data available on forming the first disulphide bond in each. It is a thermodynamic necessity that whatever conformation stabilises a particular disulphide bond be stabilised to the same extent by the presence of the disulphide. The stabilising effects of disulphides are known approximately, so the stability of any non-random conformation found in a one-disulphide intermediate can be estimated in the absence of the disulphide bond. The non-random conformation in the BPTI intermediates is sufficiently labile to indicate that it would be expected to be present in no more than 5% of the reduced BPTI molecules. There is much less non-random conformation apparent in ribonuclease A. Whatever conformations are represented in the bulk of these two reduced proteins cannot favour disulphide formation and further productive folding.