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AlphaFold predicts the most complex protein knot and composite protein knots.

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, that is, knotting. Amongst others, we discovered a 7₁ -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 5₁ -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.

SUBMITTER: Brems MA

PROVIDER: S-EPMC9278004 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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AlphaFold predicts the most complex protein knot and composite protein knots.

Brems Maarten A MA Runkel Robert R Yeates Todd O TO Virnau Peter P

Protein science : a publication of the Protein Society 20220801 8

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<sub>1</sub> -knot, the most topologically complex knot ever found in a protein, as well several six-crossing composite knots ...[more]

PMID: 35900026

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