The nature of the initial step in the conformational folding of disulphide-intact ribonuclease A.

Here we investigate conformational folding reaction of disulphide-intact ribonuclease A in the absence of the complicating effects due to non-native interactions (such as cis/trans proline isomerization) in the unfolded state. The conformational folding process is found to be intrinsically very fast occurring on the milliseconds time scale. The kinetic data indicate that the conformational folding of ribonuclease A proceeds through the formation of a hydrophobically collapsed intermediate with properties similar to those of equilibrium molten-globules. Furthermore, the data suggest that the rate-limiting transition states on the unfolding and refolding pathways are substantially different with the refolding transition state having non-native-like properties.