Circuit topology for bottom-up engineering of molecular knots

TL;DR

This paper introduces a circuit topology framework to systematically analyze and understand the structure of molecular knots, especially in proteins, using a bottom-up approach based on fundamental structural units and topological operations.

Contribution

It develops a novel circuit topology-based method to describe chain entanglement in molecular knots, revealing why prime knots are undecomposable and aiding molecular engineering.

Findings

Protein knots form a distinct group in circuit topology

Prime knots are composed of specific structural units that prevent decomposition

The approach provides a detailed understanding of molecular knot structure

Abstract

The art of tying knots is exploited in nature and occurs in multiple applications ranging from being an essential part of scouting programs to engineering molecular knots. Biomolecular knots, such as knotted proteins, bear various cellular functions and their entanglement is believed to provide them with thermal and kinetic stability. Yet, little is known about the design principles of naturally evolved molecular knots. Intra-chain contacts and chain entanglement contribute to folding of knotted proteins. Circuit topology, a theory that describes intra-chain contacts, was recently generalized to account for chain entanglement. This generalization is unique to circuit topology and not motivated by other theories. In this paper, we systematically analyze the circuit topology approach to a description of linear chain entanglement. We utilize a bottom-up approach, i.e., we express entanglement by a set of 4 fundamental structural units subjected to 3 (or 5) binary topological operations. All knots found in proteins form a well-defined, distinct group which naturally appears if expressed in terms of these basic structural units. Prime knots, which are viewed by knot theory as undecomposable, are also made of these structural units connected in some specific way. In turn, this kind of connection shows the fundamental reason why prime knots cannot be decomposed in the rigorous sense of knot theory. We believe that such a detailed, bottom-up understanding of the structure of molecular knots should be beneficial for molecular engineering.