Modeling knotted proteins with tangles

TL;DR

This paper extends a topological model of protein knot formation by incorporating crossing signs and tangle calculus, predicting likely protein knots and providing methods for engineering specific knotted proteins.

Contribution

It advances the theoretical understanding of protein knotting by integrating crossing signs into the model and applying tangle calculus to predict and engineer protein knots.

Findings

Twist knots are most likely in proteins.

Predicted knots include +3_1, 4_1, and -5_2.

Provides recipes for engineering specific knots.

Abstract

Although rare, an increasing number of proteins have been observed to contain entanglements in their native structures. To gain more insight into the significance of protein knotting, researchers have been investigating protein knot formation using both experimental and theoretical methods. Motivated by the hypothesized folding pathway of $\alpha$-haloacid dehalogenase (DehI) protein, Flapan, He, and Wong proposed a theory of how protein knots form, which includes existing folding pathways described by Taylor and B\"olinger et al. as special cases. In their topological descriptions, two loops in an unknotted open protein chain containing at most two twists each come close together, and one end of the protein eventually passes through the two loops. In this paper, we build on Flapan, He, and Wong's theory where we pay attention to the crossing signs of the threading process and assume that the unknotted protein chain may arrange itself into a more complicated configuration before threading occurs. We then apply tangle calculus, originally developed by Ernst and Sumners to analyze the action of specific proteins on DNA, to give all possible knots or knotoids that may be discovered in the future according to our model and give recipes for engineering specific knots in proteins from simpler pieces. We show why twists knots are the most likely knots to occur in proteins. We use chirality to show that the most likely knots to occur in proteins via Taylor's twisted hairpin model are the knots $+3_1$, $4_1$, and $-5_2$.