Protein Folding, Energy Landscapes and Downhill Protein Folding Scenarios
In 1968 Levinthal identified the disparity between the experimentally observed timescale of protein folding reactions and the astronomical complexity of an unguided conformational search for the native state. It was once thought that rapid folding required a unique pathway to the native conformation. However, in recent years, the discussion has seemingly shifted from “how do proteins fold so quickly?” to “why do many proteins fold so slowly?”. New perspectives on the folding process have led to an understanding that finding the native conformation is to some extent energetically downhill and, in the absence of complicating factors, can proceed rapidly by a multiplicity of parallel routes.
Also in the 1960s, it was established that protein folding was apparently a cooperative “all or none” process. This interpretation has also been challenged in recent years, and there is now considerable discussion (Muñoz et...
- Cerminara M, Campos LA, Ramanathan R, Muñoz V (2013) Slow proton transfer coupled to unfolding explains the puzzling results of single-molecule experiments on BBL, a paradigmatic downhill folding protein. PLoS One 8:e78044. https://doi.org/10.1371/journal.pone.0078044CrossRefPubMedPubMedCentralGoogle Scholar
- Kim PS, Baldwin RL (1982) Specific intermediates in the folding reactions of small proteins and the mechanism of protein folding. Annu Rev Biochem 51:459–489. https://doi.org/10.1146/annurev.bi.51.070182.002331CrossRefPubMedGoogle Scholar