Pathways to folding, nucleation events and native geometry

TL;DR

This study uses Monte Carlo simulations to explore folding pathways in proteins, revealing nucleation-driven mechanisms and how native geometry influences folding cooperativity and nucleus formation.

Contribution

It demonstrates that folding pathways are nucleation-based and that native geometry affects the folding mechanism and cooperativity in protein models.

Findings

Folding involves nucleation phenomena in both models.

More complex native geometries lead to more cooperative folding.

Folding nuclei resemble native geometry more in complex structures.

Abstract

We perform extensive Monte Carlo simulations of a lattice model and the Go potential to investigate the existence of folding pathways at the level of contact cluster formation for two native structures with markedly different geometries. Our analysis of folding pathways revealed a common underlying folding mechanism, based on nucleation phenomena, for both protein models. However, folding to the more complex geometry (i.e. that with more non-local contacts) is driven by a folding nucleus whose geometric traits more closely resemble those of the native fold. For this geometry folding is clearly a more cooperative process.