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arXiv · 2207.07410

AlphaFold predicts the most complex protein knot and composite protein knots

Maarten A. Brems·Robert Runkel·Todd O. Yeates·Peter Virnau
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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.

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Maarten A. Brems, Robert Runkel, Todd O. Yeates, Peter Virnau. 2022-07-15. AlphaFold predicts the most complex protein knot and composite protein knots. https://doi.org/10.1002/pro.4380

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