A spin-1 representation for dual-funnel energy landscapes

The interconversion between the left- and right-handed helical folds of a polypeptide defines a dual-funneled free energy landscape. In this context, the funnel minima are connected through a continuum of unfolded conformations, evocative of the classical helix-coil transition. Physical intuition an...

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Bibliographic Details
Published in:The Journal of chemical physics 2018-07, Vol.149 (3), p.035101-035101
Main Authors: Elenewski, Justin E., Velizhanin, Kirill A., Zwolak, Michael
Format: Article
Language:English
Subjects:
Free energy
INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
Ising model
Landscape architecture
Molecular dynamics
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Summary:The interconversion between the left- and right-handed helical folds of a polypeptide defines a dual-funneled free energy landscape. In this context, the funnel minima are connected through a continuum of unfolded conformations, evocative of the classical helix-coil transition. Physical intuition and recent conjectures suggest that this landscape can be mapped by assigning a left- or right-handed helical state to each residue. We explore this possibility using all-atom replica exchange molecular dynamics and an Ising-like model, demonstrating that the energy landscape architecture is at odds with a two-state picture. A three-state model—left, right, and unstructured—can account for most key intermediates during chiral interconversion. Competing folds and excited conformational states still impose limitations on the scope of this approach. However, the improvement is stark: Moving from a two-state to a three-state model decreases the fit error from 1.6 kBT to 0.3 kBT along the left-to-right interconversion pathway.
ISSN:0021-9606
1089-7690
1089-7690
DOI:10.1063/1.5036677