New 63 knot and other knots in human proteome from AlphaFold predictions

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Abstract

AlphaFold is a new, highly accurate machine learning protein structure prediction method that outperforms other methods. Recently this method was used to predict the structure of 98.5% of human proteins. We analyze here the structure of these AlphaFold-predicted human proteins for the presence of knots. We found that the human proteome contains 65 robustly knotted proteins, including the most complex type of a knot yet reported in proteins. That knot type, denoted 6 3 in mathematical notation, would necessitate a more complex folding path than any knotted proteins characterized to date. In some cases AlphaFold structure predictions are not highly accurate, which either makes their topology hard to verify or results in topological artifacts. Other structures that we found, which are knotted, potentially knotted, and structures with artifacts (knots) we deposited in a database available at: https://knotprot.cent.uw.edu.pl/alphafold .

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last seen: 2026-05-19T01:45:01.086888+00:00