Geometry of the energy landscape and folding transition in a simple model of a protein

TL;DR

This paper uses geometric analysis to study the energy landscape of a simple protein model, revealing how landscape curvature fluctuations indicate folding transitions and differentiate protein-like sequences from others.

Contribution

It introduces a geometric approach linking energy landscape curvature to folding behavior, providing a new way to analyze protein folding transitions.

Findings

Curvature fluctuations mark folding transitions.

Protein-like sequences show distinct geometric signatures.

Energy landscape geometry correlates with folding behavior.

Abstract

A geometric analysis of the global properties of the energy landscape of a minimalistic model of a polypeptide is presented, which is based on the relation between dynamical trajectories and geodesics of a suitable manifold, whose metric is completely determined by the potential energy. We consider different sequences, some with a definite protein-like behavior, a unique native state and a folding transition, and the others undergoing a hydrophobic collapse with no tendency to a unique native state. The global geometry of the energy landscape appears to contain relevant information on the behavior of the various sequences: in particular, the fluctuations of the curvature of the energy landscape, measured by means of numerical simulations, clearly mark the folding transition and allow to distinguish the protein-like sequences from the others.