Comparison between long-range interactions and contact order in determining the folding rate of two-state proteins: Application of long-range order to folding rate prediction

The contact order is believed to be an important factor for understanding p rotein folding mechanisms. In our earlier work, we have shown that the long -range interactions play a vital role in protein folding. Ln this work, we analyzed the contribution of long-range contacts to determine the folding r ate of two-state proteins. We found that the residues that are close in spa ce and are separated by at least ten to 15 residues in sequence are importa nt determinants of folding rates, suggesting the presence of a folding nucl eus at an interval of approximately 25 residues. A novel parameter "long-ra nge order" has been proposed to predict protein folding rates. This paramet er shows as good a relationship with the folding rate of two-state proteins as contact order. Further, we examined the minimum limit of residue separa tion to determine the long-range contacts for different structural classes. We observed an excellent correlation between long-range order and folding rate for all classes of globular proteins. We suggest that in mixed-class p roteins, a larger number of residues can serve as folding nuclei compared t o all-a and all-P proteins. A simple statistical method has been developed to predict the folding rates of two-state proteins using the long-range ord er that produces an agreement with experimental results that is better or c omparable to other methods in the literature. (C) 2001 Academic Press.