How to fold intricately: using theory and experiments to unravel the properties of knotted proteins

TL;DR

This paper reviews recent experimental and computational advances in understanding the folding mechanisms of knotted proteins, highlighting the interplay of thermodynamics, kinetics, and chaperone effects.

Contribution

It provides a comprehensive overview of how theory and experiments complement each other in unraveling knotted protein folding properties.

Findings

Advances in experimental methods elucidate folding pathways.

Computational models help simulate complex folding processes.

Open issues identified for future research.

Abstract

Over the years, advances in experimental and computational methods have helped us to understand the role of thermodynamic, kinetic and active (chaperone-aided) effects in coordinating the folding steps required to achieving a knotted native state. Here, we review such developments by paying particular attention to the complementarity of experimental and computational studies. Key open issues that could be tackled with either or both approaches are finally pointed out.