@article {390, title = {Hysteresis as a Marker for Complex, Overlapping Landscapes in Proteins.}, journal = {Journal of Physicak Chemistry Letters}, volume = {4}, year = {2013}, month = {2013 Jan 3}, pages = {180-188}, abstract = {Topologically complex proteins fold by multiple routes as a result of hard-to-fold regions of the proteins. Oftentimes these regions are introduced into the protein scaffold for function and increase frustration in the otherwise smooth-funneled landscape. Interestingly, while functional regions add complexity to folding landscapes, they may also contribute to a unique behavior referred to as hysteresis. While hysteresis is predicted to be rare, it is observed in various proteins, including proteins containing a unique peptide cyclization to form a fluorescent chromophore as well as proteins containing a knotted topology in their native fold. Here, hysteresis is demonstrated to be a consequence of the decoupling of unfolding events from the isomerization or hula-twist of a chromophore in one protein and the untying of the knot in a second protein system. The question now is- can hysteresis be a marker for the interplay of landscapes where complex folding and functional regions overlap?}, issn = {1948-7185}, doi = {10.1021/jz301893w}, author = {Andrews, Benjamin T and Capraro, Dominique T and Joanna I. Sulkowska and Onuchic, Jos{\'e} N and Jennings, Patricia A} }