AlphaFold predicts the most complex protein knot and composite protein knots

TL;DR

This study uses AlphaFold predictions to identify and analyze complex protein knots, discovering the most intricate knots ever found in proteins and revealing new topological structures with implications for understanding protein folding.

Contribution

We identified the most complex protein knot and several new composite knots using AlphaFold predictions, expanding knowledge of protein topologies and folding mechanisms.

Findings

Discovered a 7_1 knot, the most complex in a protein

Found multiple 6-crossing composite knots from gene duplication

Reported two new 5-crossing knots, including the first 5_1 knot

Abstract

The computer artificial intelligence system AlphaFold has recently predicted previously unknown three-dimensional structures of thousands of proteins. Focusing on the subset with high-confidence scores, we algorithmically analyze these predictions for cases where the protein backbone exhibits rare topological complexity, i.e. knotting. Amongst others, we discovered a $7_1$-knot, the most topologically complex knot ever found in a protein, as well several 6-crossing composite knots comprised of two methyltransferase or carbonic anhydrase domains, each containing a simple trefoil knot. These deeply embedded composite knots occur evidently by gene duplication and interconnection of knotted dimers. Finally, we report two new five-crossing knots including the first $5_1$-knot. Our list of analyzed structures forms the basis for future experimental studies to confirm these novel knotted topologies and to explore their complex folding mechanisms.