{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T06:57:48Z","timestamp":1793343468635,"version":"4.5.0"},"reference-count":39,"publisher":"International Union of Crystallography (IUCr)","issue":"10","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/legalcode"},{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/legalcode"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35GM131883"],"award-info":[{"award-number":["R35GM131883"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01GM063210"],"award-info":[{"award-number":["P01GM063210"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Phenix Industrial Consortium"}],"content-domain":{"domain":["iucr.org","wiley.com","iucrj.org"],"crossmark-restriction":true},"short-container-title":["Acta Crystallogr D Struct Biol","Acta Crystallogr D","Acta Cryst D","Acta Cryst D Struct Biol","Acta Cryst Sect D","Acta Cryst Sect D Struct Biol","Acta Crystallogr Sect D","Acta Crystallogr Sect D Struct Biol","Acta Crystallogr D Biol Crystallogr","Acta Cryst D Biol Cryst"],"accepted":{"date-parts":[[2025,9,3]]},"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:p>\n                    <jats:italic>AlphaFold<\/jats:italic>\n                    2 protein structure predictions are widely available for structural biology uses. These predictions, especially for eukaryotic proteins, frequently contain extensive regions predicted below the pLDDT = 70 level, the rule-of-thumb cutoff for high confidence. This work identifies major modes of behavior within low-pLDDT regions through a survey of human proteome predictions provided by the AlphaFold Protein Structure Database. The\n                    <jats:italic>near-predictive<\/jats:italic>\n                    mode resembles folded protein and can be a nearly accurate prediction.\n                    <jats:italic>Barbed wire<\/jats:italic>\n                    is extremely unprotein-like, being recognized by wide looping coils, an absence of packing contacts and numerous signature validation outliers, and it represents a region where the conformation has no predictive value.\n                    <jats:italic>Pseudostructure<\/jats:italic>\n                    presents an intermediate behavior with a misleading appearance of isolated and badly formed secondary-structure-like elements. These prediction modes are compared with annotations of disorder from MobiDB, showing general correlation between\n                    <jats:italic>barbed wire<\/jats:italic>\n                    \/\n                    <jats:italic>pseudostructure<\/jats:italic>\n                    and many measures of disorder, an association between\n                    <jats:italic>pseudostructure<\/jats:italic>\n                    and signal peptides, and an association between\n                    <jats:italic>near-predictive<\/jats:italic>\n                    and regions of conditional folding. To enable users to identify these regions within a prediction, a new\n                    <jats:italic>Phenix<\/jats:italic>\n                    tool is developed encompassing the results of this work, including prediction annotation, visual markup and residue selection based on these prediction modes. This tool will help users develop expertise in interpreting difficult\n                    <jats:italic>AlphaFold<\/jats:italic>\n                    predictions and identify the\n                    <jats:italic>near-predictive<\/jats:italic>\n                    regions that can aid in molecular replacement when a prediction does not contain enough high-pLDDT regions.\n                  <\/jats:p>","DOI":"10.1107\/s2059798325007843","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T15:40:55Z","timestamp":1757432455000},"page":"558-572","update-policy":"https:\/\/doi.org\/10.1107\/cm_01","source":"Crossref","is-referenced-by-count":10,"title":["Categorizing prediction modes within low-pLDDT regions of\n                    <i>AlphaFold<\/i>\n                    2 structures: near-predictive, pseudostructure and barbed wire"],"prefix":"10.1107","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5808-8768","authenticated-orcid":true,"given":"Christopher J.","family":"Williams","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01n9kga30","id-type":"ROR","asserted-by":"publisher"}],"department":["Department of Biochemistry"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2492-979X","authenticated-orcid":true,"given":"Vincent B.","family":"Chen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01n9kga30","id-type":"ROR","asserted-by":"publisher"}],"department":["Department of Biochemistry"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Richardson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01n9kga30","id-type":"ROR","asserted-by":"publisher"}],"department":["Department of Biochemistry"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3311-2944","authenticated-orcid":true,"given":"Jane S.","family":"Richardson","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01n9kga30","id-type":"ROR","asserted-by":"publisher"}],"department":["Department of Biochemistry"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"329","published-online":{"date-parts":[[2025,9,12]]},"reference":[{"key":"nz5018_bb1","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"nz5018_bb2","doi-asserted-by":"crossref","first-page":"2100","DOI":"10.1016\/j.jmb.2013.03.018","volume":"425","author":"Adzhubei","year":"2013","journal-title":"J. Mol. Biol."},{"key":"nz5018_bb3","doi-asserted-by":"crossref","first-page":"e2304302120","DOI":"10.1073\/pnas.2304302120","volume":"120","author":"Alderson","year":"2023","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"nz5018_bb4","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1126\/science.abj8754","volume":"373","author":"Baek","year":"2021","journal-title":"Science"},{"key":"nz5018_bb5","doi-asserted-by":"crossref","first-page":"2403","DOI":"10.1002\/pro.250","volume":"18","author":"Chen","year":"2009","journal-title":"Protein Sci."},{"key":"nz5018_bb6","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1002\/prot.26582","volume":"91","author":"Conte","year":"2023","journal-title":"Proteins"},{"key":"nz5018_bb7","doi-asserted-by":"crossref","first-page":"W375","DOI":"10.1093\/nar\/gkm216","volume":"35","author":"Davis","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"nz5018_bb8","first-page":"20250210637595","author":"Dunbrack","year":"2025","journal-title":"bioRxiv"},{"key":"nz5018_bb9","unstructured":"Engelbart, D. C. (2023). Augmented Education in the Global Age, edited by D. Araya & P. Marber, pp 13-29. New York: Routledge."},{"key":"nz5018_bb10","doi-asserted-by":"crossref","first-page":"D507","DOI":"10.1093\/nar\/gkr884","volume":"40","author":"Fukuchi","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"nz5018_bb11","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s41592-021-01365-3","volume":"19","author":"Jones","year":"2022","journal-title":"Nat. Methods"},{"key":"nz5018_bb12","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-021-03819-2","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"},{"key":"nz5018_bb13","doi-asserted-by":"crossref","first-page":"e70176","DOI":"10.1002\/pro.70176","volume":"34","author":"Krissinel","year":"2025","journal-title":"Protein Sci."},{"key":"nz5018_bb14","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1107\/S2059798319011471","volume":"75","author":"Liebschner","year":"2019","journal-title":"Acta Cryst. D"},{"key":"nz5018_bb15","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1126\/science.ade2574","volume":"379","author":"Lin","year":"2023","journal-title":"Science"},{"key":"nz5018_bb16","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1002\/prot.10286","volume":"50","author":"Lovell","year":"2003","journal-title":"Proteins"},{"key":"nz5018_bb17","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1021\/ma60030a031","volume":"5","author":"Matthews","year":"1972","journal-title":"Macromolecules"},{"key":"nz5018_bb18","doi-asserted-by":"crossref","first-page":"4061","DOI":"10.1111\/febs.12860","volume":"281","author":"Moriarty","year":"2014","journal-title":"FEBS J."},{"key":"nz5018_bb19","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1038\/s41592-021-01117-3","volume":"18","author":"Necci","year":"2021","journal-title":"Nat. Methods"},{"key":"nz5018_bb20","doi-asserted-by":"crossref","first-page":"D495","DOI":"10.1093\/nar\/gkae969","volume":"53","author":"Piovesan","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"nz5018_bb21","doi-asserted-by":"crossref","first-page":"e4466","DOI":"10.1002\/pro.4466","volume":"31","author":"Piovesan","year":"2022","journal-title":"Protein Sci."},{"key":"nz5018_bb22","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1002\/pro.3786","volume":"29","author":"Prisant","year":"2020","journal-title":"Protein Sci."},{"key":"nz5018_bb23","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0022-2836(63)80023-6","volume":"7","author":"Ramachandran","year":"1963","journal-title":"J. Mol. Biol."},{"key":"nz5018_bb24","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1038\/77912","volume":"7","author":"Richardson","year":"2000","journal-title":"Nat. Struct. Biol."},{"key":"nz5018_bb25","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1107\/S2059798323008847","volume":"79","author":"Richardson","year":"2023","journal-title":"Acta Cryst. D"},{"key":"nz5018_bb26","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1107\/S0365110X59002535","volume":"12","author":"Sasisekharan","year":"1959","journal-title":"Acta Cryst."},{"key":"nz5018_bb27","doi-asserted-by":"crossref","first-page":"W431","DOI":"10.1093\/nar\/gkab314","volume":"49","author":"Sehnal","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"nz5018_bb28","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1107\/S2059798323006289","volume":"79","author":"Simpkin","year":"2023","journal-title":"Acta Cryst. D"},{"key":"nz5018_bb29","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1107\/S2059798325001251","volume":"81","author":"Simpkin","year":"2025","journal-title":"Acta Cryst. D"},{"key":"nz5018_bb30","doi-asserted-by":"crossref","first-page":"2300176","DOI":"10.1002\/pmic.202300176","volume":"23","author":"Tam","year":"2023","journal-title":"Proteomics"},{"key":"nz5018_bb31","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1107\/S205979832300102X","volume":"79","author":"Terwilliger","year":"2023","journal-title":"Acta Cryst. D"},{"key":"nz5018_bb32","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/s41592-023-02087-4","volume":"21","author":"Terwilliger","year":"2024","journal-title":"Nat. Methods"},{"key":"nz5018_bb33","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1126\/science.abc8665","volume":"369","author":"Thoms","year":"2020","journal-title":"Science"},{"key":"nz5018_bb34","doi-asserted-by":"crossref","first-page":"1666","DOI":"10.1038\/s41591-021-01533-0","volume":"27","author":"Thornton","year":"2021","journal-title":"Nat. Med."},{"key":"nz5018_bb35","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1038\/s41586-021-03828-1","volume":"596","author":"Tunyasuvunakool","year":"2021","journal-title":"Nature"},{"key":"nz5018_bb36","doi-asserted-by":"crossref","first-page":"D368","DOI":"10.1093\/nar\/gkad1011","volume":"52","author":"Varadi","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"nz5018_bb37","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1107\/S2059798324011999","volume":"81","author":"Wang","year":"2025","journal-title":"Acta Cryst. D"},{"key":"nz5018_bb38","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1002\/pro.3330","volume":"27","author":"Williams","year":"2018","journal-title":"Protein Sci."},{"key":"nz5018_bb39","doi-asserted-by":"crossref","first-page":"4591","DOI":"10.3390\/ijms23094591","volume":"23","author":"Wilson","year":"2022","journal-title":"Int. J. Mol. Sci."}],"container-title":["Acta Crystallographica Section D Structural Biology"],"original-title":[],"link":[{"URL":"https:\/\/journals.iucr.org\/d\/issues\/2025\/10\/00\/nz5018\/nz5018.pdf","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.iucr.org\/d\/issues\/2025\/10\/00\/nz5018\/nz5018.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T13:32:39Z","timestamp":1761312759000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.iucr.org\/paper?S2059798325007843"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,12]]},"references-count":39,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["S2059798325007843"],"URL":"https:\/\/doi.org\/10.1107\/s2059798325007843","relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.1107\/S2059798325007843\/nz5018sup1.pdf","asserted-by":"subject"},{"id-type":"doi","id":"10.1107\/S2059798325007843\/nz5018sup2.xlsx","asserted-by":"subject"}]},"ISSN":["2059-7983"],"issn-type":[{"value":"2059-7983","type":"print"}],"subject":[],"published":{"date-parts":[[2025,9,12]]},"assertion":[{"value":"Acta Crystallographica Section D: Structural Biology","order":0,"name":"journal","label":"Publication","explanation":{"URL":"https:\/\/journals.iucr.org\/d"},"group":{"name":"general","label":"General"}},{"value":"research papers","order":1,"name":"content_type","label":"Content type","explanation":{"URL":"https:\/\/journals.iucr.org\/d\/services\/notesforauthors.html"},"group":{"name":"general","label":"General"}},{"value":"Available","URL":"https:\/\/scripts.iucr.org\/cgi-bin\/citedin?nz5018","order":2,"name":"article_metrics","label":"Article metrics","group":{"name":"general","label":"General"}},{"value":"Yes","order":0,"name":"peer_reviewed","label":"Peer reviewed","group":{"name":"peer_review","label":"Peer review"}},{"value":"Single blind","order":1,"name":"review_process","label":"Review process","group":{"name":"peer_review","label":"Peer review"}},{"value":"6 June 2025","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication history"}},{"value":"3 September 2025","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication history"}},{"value":"12 September 2025","order":2,"name":"published_online","label":"Published online","group":{"name":"publication_history","label":"Publication history"}},{"value":"This article has supporting information","name":"supplementary_materials","label":"Supplementary materials","explanation":{"URL":"https:\/\/scripts.iucr.org\/cgi-bin\/sendsup?nz5018"}},{"value":"\u00a9 2025 Christopher J. Williams\n                      et al.","order":0,"name":"copyright","label":"Copyright","explanation":{"URL":"https:\/\/journals.iucr.org\/services\/copyrightpolicy.html"},"group":{"name":"copyright_and_licencing","label":"Copyright and licencing"}},{"value":"Creative Commons Attribution (CC-BY)","order":1,"name":"license","label":"Licence","explanation":{"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/legalcode"},"group":{"name":"copyright_and_licencing","label":"Copyright and licencing"}}]}}