Cooperativity and modularity in protein folding

A simple statistical mechanical model proposed by Wako and Saito has explained the aspects of protein folding surprisingly well. This model was systematically applied to multiple proteins by Munoz and Eaton and has since been referred to as the Wako-Saito-Munoz-Eaton (WSME) model. The success of the WSME model in explaining the folding of many proteins has verified the hypothesis that the folding is dominated by native interactions, which makes the energy landscape globally biased toward native conformation. Using the WSME and other related models, Saito emphasized the importance of the hierarchical pathway in protein folding; folding starts with the creation of contiguous segments having a