{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T20:11:57Z","timestamp":1793391117776,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1011959","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T00:00:00Z","timestamp":1719878400000}}],"reference-count":61,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T00:00:00Z","timestamp":1718841600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2018\/31\/B\/NZ1\/04016; 2021\/43\/I\/NZ1\/03341"],"award-info":[{"award-number":["2018\/31\/B\/NZ1\/04016; 2021\/43\/I\/NZ1\/03341"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004239","name":"Poznan University of Technology","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004239","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100020811","name":"Instytut Chemii Bioorganicznej, Polskiej Akademii Nauk","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020811","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Unlike proteins, RNAs deposited in the Protein Data Bank do not contain topological knots. Recently, admittedly, the first trefoil knot and some lasso-type conformations have been found in experimental RNA structures, but these are still exceptional cases. Meanwhile, algorithms predicting 3D RNA models have happened to form knotted structures not so rarely. Interestingly, machine learning-based predictors seem to be more prone to generate knotted RNA folds than traditional methods. A similar situation is observed for the entanglements of structural elements. In this paper, we analyze all models submitted to the CASP15 competition in the 3D RNA structure prediction category. We show what types of topological knots and structure element entanglements appear in the submitted models and highlight what methods are behind the generation of such conformations. We also study the structural aspect of susceptibility to entanglement. We suggest that predictors take care of an evaluation of RNA models to avoid publishing structures with artifacts, such as unusual entanglements, that result from hallucinations of predictive algorithms.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1011959","type":"journal-article","created":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T13:42:05Z","timestamp":1718890925000},"page":"e1011959","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Knotted artifacts in predicted 3D RNA structures"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9971-6807","authenticated-orcid":true,"given":"Bartosz 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Invariants of links of Conway type. arXiv [pre-print] arXiv:161006679. 2016;."},{"key":"pcbi.1011959.ref054","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.ejc.2017.06.004","article-title":"New invariants of knotoids","volume":"65","author":"N G\u00fcg\u00fcmc\u00fc","year":"2017","journal-title":"Eur J Comb"},{"issue":"19","key":"pcbi.1011959.ref055","doi-asserted-by":"crossref","first-page":"3402","DOI":"10.1093\/bioinformatics\/bty365","article-title":"Knoto-ID: a tool to study the entanglement of open protein chains using the concept of knotoids","volume":"34","author":"J Dorier","year":"2018","journal-title":"Bioinformatics"},{"issue":"2240","key":"pcbi.1011959.ref056","first-page":"20200124","article-title":"Knot polynomials of open and closed curves","volume":"476","author":"E Panagiotou","year":"2020","journal-title":"P Roy Soc A"},{"issue":"2","key":"pcbi.1011959.ref057","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1042\/BST20120339","article-title":"Identifying knots in proteins","volume":"41","author":"KC Millett","year":"2013","journal-title":"Biochem Soc Trans"},{"issue":"4","key":"pcbi.1011959.ref058","doi-asserted-by":"crossref","first-page":"2873","DOI":"10.1063\/1.460889","article-title":"Self-entanglement in ring polymers","volume":"95","author":"K Koniaris","year":"1991","journal-title":"J Chem Phys"},{"issue":"2","key":"pcbi.1011959.ref059","doi-asserted-by":"crossref","first-page":"022502","DOI":"10.1103\/PhysRevE.101.022502","article-title":"Identifying knot types of polymer conformations by machine learning","volume":"101","author":"O Vandans","year":"2020","journal-title":"Phys Rev E"},{"issue":"2","key":"pcbi.1011959.ref060","doi-asserted-by":"crossref","first-page":"025035","DOI":"10.1088\/2632-2153\/abe91f","article-title":"Learning to unknot","volume":"2","author":"S Gukov","year":"2021","journal-title":"Mach Learn Sci Technol"},{"key":"pcbi.1011959.ref061","article-title":"Knots and \u03b8-Curves Identification in Polymeric Chains and Native Proteins Using Neural Networks","author":"F Bruno da Silva","year":"2024","journal-title":"Macromolecules"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1011959","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T00:00:00Z","timestamp":1719878400000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1011959","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T15:30:31Z","timestamp":1719934231000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1011959"}},"subtitle":[],"editor":[{"given":"Shi-Jie","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,6,20]]},"references-count":61,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,6,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1011959","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2024.03.04.583268","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,20]]}}}