# Topological transformations in proteins: effects of heating and proximity of an interface

## TL;DR

This study investigates how heating and proximity to an interface affect the unfolding and knotting of proteins using a coarse-grained model, revealing temperature-dependent mechanisms and interface-induced knot untying or formation.

## Contribution

It introduces a model to analyze the effects of temperature and interfaces on protein knot dynamics, highlighting distinct unfolding pathways and interface-induced knotting behaviors.

## Key findings

- High temperature causes unfolding via loop untying.
- Interfaces can untie shallow knots and induce knot formation.
- Untying knots generally precedes unfolding unless deeply knotted.

## Abstract

Using a structure-based coarse-grained model of proteins, we study the mechanism of unfolding of knotted proteins through heating. We find that the dominant mechanisms of unfolding depend on the temperature applied and are generally distinct from those identified for folding at its optimal temperature. In particular, for shallowly knotted proteins, folding usually involves formation of two loops whereas unfolding through high-temperature heating is dominated by untying of single loops. Untying the knots is found to generally precede unfolding unless the protein is deeply knotted and the heating temperature exceeds a threshold value. We then use a phenomenological model of the air-water interface to show that such an interface can untie shallow knots, but it can also make knots in proteins that are natively unknotted.