title: Hysteresis as a Marker for Complex, Overlapping Landscapes in Proteins.
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?
authors.affiliation: Department of Medicinal Chemistry, University of Washington, Seattle, WA.
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Andrews
authors.forename: Dominique T
authors.initials: DT
authors.lastname: Capraro
authors.forename: Joanna I
authors.initials: JI
authors.lastname: Sulkowska
authors.forename: José N
authors.initials: JN
authors.lastname: Onuchic
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Jennings
keywords: Energy Landscape; Interplay; Knotted Proteins; Protein Folding