Figure 3.

Intramolecular reshuffling reactions within the 3S ensemble compete with the conformational folding reaction in the rate-determining, structure-forming step of RNase A. Reshuffling of native-disulfide-bond-containing 3S species (all green bonds), which is shown to reside orthogonal to the trajectory to N, results in the formation of non-native disulfide-bond-containing species (red ± green bonds). By contrast, 3S species with all native disulfide bonds can conformationally fold to the structured 3S* species that protect the native bonds from undergoing isomerization reactions.