A Spin-1 Representation for Dual-Funnel Energy Landscapes

TL;DR

This paper introduces a three-state model (left, right, unstructured) for dual-funnel energy landscapes of polypeptides, improving the understanding of chiral interconversion beyond traditional two-state models.

Contribution

It demonstrates that a three-state model better captures the energy landscape of polypeptide chiral interconversion than the conventional two-state approach.

Findings

Three-state model reduces fit error significantly.

Energy landscape is inconsistent with a simple two-state picture.

All-atom simulations support the three-state representation.

Abstract

The interconversion between 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.