Clash between energy landscape theory and foldon-dependent protein folding

In PNAS, Englander and Mayne (1) review their earlier published evidence that proteins fold and unfold by foldons. The foldon evidence indicates that protein folding follows single folding pathways because the pathways are foldon-directed. The authors point out an important clash between foldon-dependent folding and using energy landscape theory (ELT) to describe folding: ELT indicates that protein folding occurs on many independent pathways even for foldon-directed folding. This basic conflict needs to be resolved to understand the nature of the protein folding process.