Sequence determines degree of knottedness in a coarse-grained protein model

TL;DR

This study investigates how amino acid sequence influences knot formation in proteins using a lattice model, revealing that sequence variability significantly affects entanglement and can be designed to control knotting.

Contribution

It demonstrates that sequence design can modulate the likelihood of knot formation in proteins within a simplified lattice model, highlighting the role of sequence in protein topology.

Findings

Sequence variability causes large differences in knotting propensity.

Sequences can be engineered to be almost always or never knotted.

Sequence acts as an additional degree of freedom influencing protein topology.

Abstract

Knots are abundant in globular homopolymers but rare in globular proteins. To shed new light on this long-standing conundrum, we study the influence of sequence on the formation of knots in proteins under native conditions within the framework of the hydrophobic-polar (HP) lattice protein model. By employing large scale Wang-Landau simulations combined with suitable Monte Carlo trial moves we show that, even though knots are still abundant on average, sequence introduces large variability in the degree of self-entanglements. Moreover, we are able to design sequences which are either almost always or almost never knotted. Our findings serve as proof of concept that the introduction of just one additional degree of freedom per monomer (in our case sequence) facilitates evolution towards a protein universe in which knots are rare.