AlphaFold predicts the most complex protein knot and composite protein knots

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, that is, knotting. Amongst others, we discovered a 7(1)-knot, the most topologically complex knot ever found in a protein, as well several six-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.

Automated summary

The computer artificial intelligence system AlphaFold has predicted previously unknown three-dimensional structure of thousands of proteins. Among these predictions, it has discovered the most topologically complex knot ever found in a protein, as well as several composite knots formed by gene duplication and interconnection of knotted dimers. Two new five-crossing knots have also been reported. These results provide a basis for future experimental studies to confirm these novel-knotted topologies and explore their folding mechanisms.