Correlation between protein stability cores and protein folding kinetics: a case study on Pseudomonas aeruginosa apo-azurin.

This paper reports a combined computational and experimental study of the correlation between protein stability cores and folding kinetics. An empirical potential function was developed, and it was used for analyzing interaction energies among secondary structure elements. Studies on a beta sandwich protein, Pseudomonas aeruginosa azurin, showed that the computationally identified substructure with the strongest interactions in the native state is identical to the "interlocked pair" of beta strands, an invariant motif found in most sandwich-like proteins. Moreover, previous and new in vitro folding results revealed that the identified substructure harbors most residues that form native-like interactions in the folding transition state. These observations demonstrate that the potential function is effective in revealing the relative strength of interactions among various protein parts; they also strengthen the suggestion that the most stable regions in native proteins favor stable interactions early during folding.