Folding and form: Insights from lattice simulations

TL;DR

This study uses lattice-polymer Monte Carlo simulations to reveal two distinct folding mechanisms in protein models, influenced by native structure geometry, with implications for understanding folding cooperativity and contact order effects.

Contribution

It provides new insights into how native structure geometry influences folding pathways and mechanisms in lattice-polymer models, highlighting the roles of contact range and intermediate contacts.

Findings

Low contact order structures fold progressively with native-like contacts.

High contact order structures fold cooperatively with non-native intermediate contacts.

Folding mechanisms are strongly dependent on native structure geometry.

Abstract

Monte Carlo simulations of a Miyazawa-Jernigan lattice-polymer model indicate that, depending on the native's structure geometry, the model exhibits two broad classes of folding mechanisms for two-state folders. Folding to native structures of low contact order is driven by contact range and is characterised by progressive accumulation of structure towards the native fold. By contrast, folding to high contact order targets is largely dominated by intermediate stage contacts which are not present in the native fold, yielding a more cooperative folding process.