A spin-1 representation for dual-funnel energy landscapes
JE Elenewski and KA Velizhanin and M Zwolak, JOURNAL OF CHEMICAL PHYSICS, 149, 035101 (2018).
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 k(B)T to 0.3 k(B)T along the left-to-right interconversion pathway. Published by AIP Publishing.
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