Exploring proteins multi-funnel energy landscape

TL;DR

This paper demonstrates that protein energy landscapes are multi-funnel shaped, with multiple stable alternative structures, challenging traditional views and proposing a new two-step folding process consistent with experimental data.

Contribution

It introduces the concept of a multi-funnel energy landscape for proteins and suggests a two-step folding mechanism, expanding understanding beyond Anfinsen's hypothesis.

Findings

Proteins can have multiple stable alternative structures.

The energy landscape of proteins is multi-funnel-shaped.

A two-step folding process is proposed and supported by experimental evidence.

Abstract

An all-atom model of proteins is used to show that the same sequence of amino acids can have many alternative structures, that are very distant from, and that can be as stable as, the corresponding native structure. Such alternative structures are not easily rationalized as belonging to the native basin and indicate instead that the free energy landscape of proteins is multi-funnel-shaped and that Anfinsen's thermodynamic hypothesis alone cannot explain protein folding. An alternative two-step process for folding is proposed and its consistency with the experimental evidence available is discussed.