Better theoretical models and protein design experiments can help to understand protein folding

In our study, we have concluded that two proteins with 88% homology choose different energetically favorable pathways in the very early stage of the folding process to attain their native folds. Subsequent reports from other investigators by performing folding and unfolding kinetics experiments concur with our findings. We herewith discuss the key papers revealing computational and experimental analysis of two designed proteins with similar sequence distant folds. Further we suggest that the theoretical/computational analysis of protein sequences and structures along with the relevant experiments provide a better understanding of the relationship between protein sequence, folding, and structure.