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Most complex protein knots

July 14, 2022
Johannes Gutenberg Universitaet Mainz
Theoretical physicists put Google's artificial intelligence AlphaFold to the test and find the most complex protein knots so far.

Theoretical physicists at Johannes Gutenberg University Mainz have put Google's artificial intelligence AlphaFold to the test and have found the most complex protein knots so far.

The question of how the chemical composition of a protein, the amino acid sequence, determines its 3D structure has been one of the biggest challenges in biophysics for more than half a century. This knowledge about the so-called "folding" of proteins is in great demand, as it contributes significantly to the understanding of various diseases and their treatment, among other things. For these reasons, Google's DeepMind research team has developed AlphaFold, an artificial intelligence that predicts 3D structures.

A team consisting of researchers from Johannes Gutenberg University Mainz (JGU) and the University of California, Los Angeles, has now taken a closer look at these structures and examined them with respect to knots. We know knots primarily from shoelaces and cables, but they also occur on the nanoscale in our cells. Knotted proteins can not only be used to assess the quality of structure predictions but also raise important questions about folding mechanisms and the evolution of proteins.

The most complex knots as a test for AlphaFold

"We investigated numerically all -- that is some 100,000 -- predictions of AlphaFold for new protein knots," said Maarten A. Brems, a PhD student in the group of Dr. Peter Virnau at Mainz University. The goal was to identify rare, high-quality structures containing complex and previously unknown protein knots to provide a basis for experimental verification of AlphaFold's predictions. The study not only discovered the most complex knotted protein to date but also the first composite knots in proteins. The latter can be thought of as two separate knots on the same string. "These new discoveries also provide insight into the evolutionary mechanisms behind such rare proteins," added Robert Runkel, a theoretical physicist also involved in the project. The results of this study were recently published in Protein Science.

Dr. Peter Virnau is pleased with the results: "We have already established a collaboration with our colleague Todd Yeates from UCLA to confirm these structures experimentally. This line of research will shape the biophysics community's view of artificial intelligence -- and we are fortunate to have an expert like Dr. Yeates involved."

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Materials provided by Johannes Gutenberg Universitaet Mainz. Note: Content may be edited for style and length.

Journal References:

  1. Maarten A. Brems, Robert Runkel, Todd O. Yeates, Peter Virnau. AlphaFold predicts the most complex protein knot and composite protein knots. Protein Science, 2022; 31 (8) DOI: 10.1002/pro.4380
  2. John Jumper, Richard Evans, Alexander Pritzel, Tim Green, Michael Figurnov, Olaf Ronneberger, Kathryn Tunyasuvunakool, Russ Bates, Augustin Žídek, Anna Potapenko, Alex Bridgland, Clemens Meyer, Simon A. A. Kohl, Andrew J. Ballard, Andrew Cowie, Bernardino Romera-Paredes, Stanislav Nikolov, Rishub Jain, Jonas Adler, Trevor Back, Stig Petersen, David Reiman, Ellen Clancy, Michal Zielinski, Martin Steinegger, Michalina Pacholska, Tamas Berghammer, Sebastian Bodenstein, David Silver, Oriol Vinyals, Andrew W. Senior, Koray Kavukcuoglu, Pushmeet Kohli, Demis Hassabis. Highly accurate protein structure prediction with AlphaFold. Nature, 2021; 596 (7873): 583 DOI: 10.1038/s41586-021-03819-2

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Johannes Gutenberg Universitaet Mainz. "Most complex protein knots." ScienceDaily. ScienceDaily, 14 July 2022. <>.
Johannes Gutenberg Universitaet Mainz. (2022, July 14). Most complex protein knots. ScienceDaily. Retrieved July 14, 2024 from
Johannes Gutenberg Universitaet Mainz. "Most complex protein knots." ScienceDaily. (accessed July 14, 2024).

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