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A spin-1 representation for dual-funnel energy landscapes.

ABSTRACT: 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_BT to 0.3 k_BT along the left-to-right interconversion pathway.

SUBMITTER: Elenewski JE

PROVIDER: S-EPMC7723752 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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A spin-1 representation for dual-funnel energy landscapes.

Elenewski Justin E JE Velizhanin Kirill A KA Zwolak Michael M

The Journal of chemical physics 20180701 3

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 ...[more]

PMID: 30037251

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