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Proteins containing 6-crossing knot types and their folding pathways

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dc.abstract.enStudying complex protein knots can provide new insights into potential knot folding mechanisms and other fundamental aspects of why and how proteins knot. This paper presents results of a systematic analysis of the 3D structure of proteins with 6-crossings knots predicted by the artificial intelligence program AlphaFold 2. Furthermore, using a coarse-grained native based model, we found that three representative proteins can self tie to a 63 knot, the most complex knot found in a protein thus far. Because it is not a twist knot, the 63 knot cannot be folded via a simple mechanism involving the threading of a single loop. Based on successful trajectories for each protein, we determined that the 63 knot is formed after folding a significant part of the protein backbone to the native conformation. Moreover, we found that there are two distinct knotting mechanisms, which are described here. Also, building on a loop flipping theory developed earlier, we present two new theories of protein folding involving the creation and threading of two loops, and explain how our theories can describe the successful folding trajectories for each of the three representative 63-knotted proteins.Competing Interest StatementThe authors have declared no competing interest.
dc.affiliationUniwersytet Warszawski
dc.affiliation.departmentWydział Matematyki, Informatyki i Mechaniki
dc.affiliation.departmentWydział Fizyki
dc.affiliation.otherCentrum Nowych Technologii UW CeNT
dc.affiliation.otherMiędzywydziałowe Indywidualne Studia Matematyczno-Przyrodnicze
dc.contributor.authorSikora, Maciej
dc.contributor.authorFlapan, Erica
dc.contributor.authorWong, Helen
dc.contributor.authorRubach, Paweł
dc.contributor.authorGarstka, Maciej
dc.contributor.authorNiewieczerzał, Szymon
dc.contributor.authorRawdon, Eric J.
dc.contributor.authorSułkowska, Joanna
dc.date.accessioned2024-10-29T07:44:52Z
dc.date.available2024-10-29T07:44:52Z
dc.date.issued2023-06-18
dc.description.abstract<jats:title>Abstract</jats:title><jats:p>Studying complex protein knots can provide new insights into potential knot folding mechanisms and other fundamental aspects of why and how proteins knot. This paper presents results of a systematic analysis of the 3D structure of proteins with 6-crossings knots predicted by the artificial intelligence program AlphaFold 2. Furthermore, using a coarse-grained native based model, we found that three representative proteins can self tie to a 6<jats:sub>3</jats:sub>knot, the most complex knot found in a protein thus far. Because it is not a twist knot, the 6<jats:sub>3</jats:sub>knot cannot be folded via a simple mechanism involving the threading of a single loop. Based on successful trajectories for each protein, we determined that the 6<jats:sub>3</jats:sub>knot is formed after folding a significant part of the protein backbone to the native conformation. Moreover, we found that there are two distinct knotting mechanisms, which are described here. Also, building on a<jats:italic>loop flipping theory</jats:italic>developed earlier, we present two new theories of protein folding involving the creation and threading of two loops, and explain how our theories can describe the successful folding trajectories for each of the three representative 6<jats:sub>3</jats:sub>-knotted proteins.</jats:p>
dc.description.grantnumber#UMO-2018/31/B/NZ1/04016
dc.description.grantnumber2021/43/I/NZ1/03341
dc.description.grantnumberDMS-1906323
dc.description.grantnumber#822014
dc.description.granttitleNational Science Centre
dc.description.granttitleNational Science Centre
dc.description.granttitleCOST EUTOPIA action, the National Science Foundation
dc.description.granttitleSimons Foundation
dc.description.number2023.06.16.545156
dc.description.versionfinal_author
dc.identifier.doihttps://doi.org/10.1101/2023.06.16.545156
dc.identifier.orcid0009-0003-0289-276X
dc.identifier.orcid0000-0002-3935-8523
dc.identifier.orcid0000-0002-9668-0332
dc.identifier.orcid0000-0001-5487-609X
dc.identifier.orcid0000-0002-7563-7212
dc.identifier.orcid0000-0002-7190-8193
dc.identifier.orcid0000-0003-2452-0724
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/160568
dc.languageen
dc.pbn.affiliationbiological sciences
dc.relation.ispartofBioArxiv
dc.relation.pages-
dc.rightsCC-BY
dc.sciencecloudsend
dc.share.typeOPEN_REPOSITORY
dc.subject.enKnots in proteins
dc.titleProteins containing 6-crossing knot types and their folding pathways
dc.typeJournalArticle
dspace.entity.typePublication