{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T15:58:21Z","timestamp":1778515101632,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1008798","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,4,27]],"date-time":"2021-04-27T00:00:00Z","timestamp":1619481600000}}],"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:00:00Z","timestamp":1618444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020 research and innovation programme under the Marie Sk\u0142odowska-Curie","award":["823886"],"award-info":[{"award-number":["823886"]}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"crossref","award":["VR-NT 2016-03798"],"award-info":[{"award-number":["VR-NT 2016-03798"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"crossref"}]},{"name":"SNIC","award":["2020\/5-300"],"award-info":[{"award-number":["2020\/5-300"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>Repeat proteins are abundant in eukaryotic proteomes. They are involved in many eukaryotic specific functions, including signalling. For many of these proteins, the structure is not known, as they are difficult to crystallise. Today, using direct coupling analysis and deep learning it is often possible to predict a protein\u2019s structure. However, the unique sequence features present in repeat proteins have been a challenge to use direct coupling analysis for predicting contacts. Here, we show that deep learning-based methods (trRosetta, DeepMetaPsicov (DMP) and PconsC4) overcomes this problem and can predict intra- and inter-unit contacts in repeat proteins. In a benchmark dataset of 815 repeat proteins, about 90% can be correctly modelled. Further, among 48 PFAM families lacking a protein structure, we produce models of forty-one families with estimated high accuracy.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1008798","type":"journal-article","created":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T11:38:36Z","timestamp":1618573116000},"page":"e1008798","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Accurate contact-based modelling of repeat proteins predicts the structure of new repeats protein families"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7161-9028","authenticated-orcid":true,"given":"Claudio","family":"Bassot","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7115-9751","authenticated-orcid":true,"given":"Arne","family":"Elofsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,4,15]]},"reference":[{"key":"pcbi.1008798.ref001","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/S0959-440X(98)80068-7","article-title":"Detection of internal repeats: how common are they?","volume":"8","author":"J Heringa","year":"1998","journal-title":"Curr Opin Struct Biol"},{"key":"pcbi.1008798.ref002","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/365274a0","article-title":"Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair","volume":"365","author":"M Strand","year":"1993","journal-title":"Nature"},{"key":"pcbi.1008798.ref003","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1128\/MCB.18.4.2045","article-title":"Expansions and Contractions in a Tandem Repeat Induced by Double-Strand Break Repair","author":"F P\u00e2ques","year":"1998","journal-title":"Molecular and Cellular Biology"},{"key":"pcbi.1008798.ref004","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1093\/molbev\/msu062","article-title":"Deep conservation of human protein tandem repeats within the eukaryotes","volume":"31","author":"E Schaper","year":"2014","journal-title":"Mol Biol Evol"},{"key":"pcbi.1008798.ref005","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1006\/jmbi.1999.3136","article-title":"A census of protein repeats","volume":"293","author":"E.M. Marcotte","year":"1999","journal-title":"J Mol Biol"},{"key":"pcbi.1008798.ref006","doi-asserted-by":"crossref","first-page":"e114","DOI":"10.1371\/journal.pcbi.0020114","article-title":"Expansion of protein domain repeats.","volume":"2","author":"AK Bj\u00f6rklund","year":"2006","journal-title":"PLoS Comput Biol"},{"key":"pcbi.1008798.ref007","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1006\/jsbi.2001.4392","article-title":"Protein Repeats: Structures, Functions, and Evolution.","author":"MA Andrade","year":"2001","journal-title":"Journal of Structural Biology"},{"key":"pcbi.1008798.ref008","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.tibs.2010.04.003","article-title":"WD40 proteins propel cellular networks","volume":"35","author":"CU Stirnimann","year":"2010","journal-title":"Trends Biochem Sci"},{"key":"pcbi.1008798.ref009","doi-asserted-by":"crossref","first-page":"15168","DOI":"10.1021\/bi062188q","article-title":"Ankyrin repeat: a unique motif mediating protein-protein interactions","volume":"45","author":"J Li","year":"2006","journal-title":"Biochemistry"},{"key":"pcbi.1008798.ref010","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1110\/ps.03554604","article-title":"The ankyrin repeat as molecular architecture for protein recognition","volume":"13","author":"LK Mosavi","year":"2004","journal-title":"Protein Sci"},{"key":"pcbi.1008798.ref011","doi-asserted-by":"crossref","first-page":"13570","DOI":"10.1038\/ncomms13570","article-title":"Positive and strongly relaxed purifying selection drive the evolution of repeats in proteins","volume":"7","author":"E Persi","year":"2016","journal-title":"Nat Commun"},{"key":"pcbi.1008798.ref012","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1006\/jsbi.2000.4328","article-title":"Review: Proteins with Repeated Sequence\u2014Structural Prediction and Modeling","author":"AV Kajava","year":"2001","journal-title":"Journal of Structural Biology"},{"key":"pcbi.1008798.ref013","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.jsb.2011.08.009","article-title":"Tandem repeats in proteins: From sequence to structure","author":"AV Kajava","year":"2012","journal-title":"Journal of Structural Biology"},{"key":"pcbi.1008798.ref014","doi-asserted-by":"crossref","first-page":"3613","DOI":"10.1093\/nar\/gkw1268","article-title":"RepeatsDB 2.0: improved annotation, classification, search and visualization of repeat protein structures","volume":"45","author":"L Paladin","year":"2017","journal-title":"Nucleic Acids Res"},{"issue":"Suppl 1","key":"pcbi.1008798.ref015","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1002\/prot.25423","article-title":"Assessment of hard target modeling in CASP12 reveals an emerging role of alignment-based contact prediction methods","volume":"86","author":"LA Abriata","year":"2018","journal-title":"Proteins"},{"key":"pcbi.1008798.ref016","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1006\/jmbi.1997.1198","article-title":"Correlated mutations contain information about protein-protein interaction","volume":"271","author":"F Pazos","year":"1997","journal-title":"J Mol Biol"},{"key":"pcbi.1008798.ref017","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1186\/s12859-015-0648-3","article-title":"Capturing coevolutionary signals inrepeat proteins","volume":"16","author":"R Espada","year":"2015","journal-title":"BMC Bioinformatics"},{"key":"pcbi.1008798.ref018","article-title":"PconsC4: fast, accurate, and hassle-free contact predictions","author":"M Michel","year":"2018","journal-title":"Bioinformatics"},{"key":"pcbi.1008798.ref019","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1073\/pnas.1914677117","article-title":"Improved protein structure prediction using predicted interresidue orientations","volume":"117","author":"J Yang","year":"2020","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pcbi.1008798.ref020","doi-asserted-by":"crossref","first-page":"3977","DOI":"10.1038\/s41467-019-11994-0","article-title":"Deep learning extends de novo protein modelling coverage of genomes using iteratively predicted structural constraints.","volume":"10","author":"JG Greener","year":"2019","journal-title":"Nat Commun"},{"key":"pcbi.1008798.ref021","doi-asserted-by":"crossref","first-page":"e92721","DOI":"10.1371\/journal.pone.0092721","article-title":"Fast and accurate multivariate Gaussian modeling of protein families: predicting residue contacts and protein-interaction partners.","volume":"9","author":"C Baldassi","year":"2014","journal-title":"PLoS One."},{"key":"pcbi.1008798.ref022","doi-asserted-by":"crossref","first-page":"2354","DOI":"10.1110\/ps.08501","article-title":"Pcons: a neural-network-based consensus predictor that improves fold recognition","volume":"10","author":"J Lundstr\u00f6m","year":"2001","journal-title":"Protein Sci"},{"key":"pcbi.1008798.ref023","doi-asserted-by":"crossref","first-page":"2647","DOI":"10.1093\/bioinformatics\/btaa058","article-title":"QMEANDisCo-distance constraints applied on model quality estimation","volume":"36","author":"G Studer","year":"2020","journal-title":"Bioinformatics"},{"key":"pcbi.1008798.ref024","doi-asserted-by":"crossref","first-page":"e1003889","DOI":"10.1371\/journal.pcbi.1003889","article-title":"Improved contact predictions using the recognition of protein like contact patterns.","volume":"10","author":"MJ Skwark","year":"2014","journal-title":"PLoS Comput Biol"},{"key":"pcbi.1008798.ref025","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1002\/prot.24829","article-title":"CONFOLD: Residue-residue contact-guided ab initio protein folding","volume":"83","author":"B Adhikari","year":"2015","journal-title":"Proteins"},{"key":"pcbi.1008798.ref026","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1093\/bioinformatics\/btq007","article-title":"PyRosetta: a script-based interface for implementing molecular modeling algorithms using Rosetta","volume":"26","author":"S Chaudhury","year":"2010","journal-title":"Bioinformatics"},{"key":"pcbi.1008798.ref027","doi-asserted-by":"crossref","first-page":"W252","DOI":"10.1093\/nar\/gku340","article-title":"SWISS-MODEL: modelling protein tertiary and quaternary structure using evolutionary information","volume":"42","author":"M Biasini","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"pcbi.1008798.ref028","doi-asserted-by":"crossref","first-page":"W296","DOI":"10.1093\/nar\/gky427","article-title":"SWISS-MODEL: homology modelling of protein structures and complexes","volume":"46","author":"A Waterhouse","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"pcbi.1008798.ref029","doi-asserted-by":"crossref","first-page":"D427","DOI":"10.1093\/nar\/gky995","article-title":"The Pfam protein families database in 2019","volume":"47","author":"S El-Gebali","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"pcbi.1008798.ref030","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1471-2180-3-3","article-title":"New knowledge from old: in silico discovery of novel protein domains in Streptomyces coelicolor","volume":"3","author":"C Yeats","year":"2003","journal-title":"BMC Microbiol"},{"key":"pcbi.1008798.ref031","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1016\/0022-2836(91)90695-3","article-title":"Proline kinks in transmembrane alpha-helices","volume":"218","author":"G von Heijne","year":"1991","journal-title":"J Mol Biol"},{"key":"pcbi.1008798.ref032","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/S0006-3495(04)74088-6","article-title":"Ser and Thr Residues Modulate the Conformation of Pro-Kinked Transmembrane \u03b1-Helices","author":"X Deupi","year":"2004","journal-title":"Biophysical Journal"},{"key":"pcbi.1008798.ref033","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/dvdy.10131","article-title":"Localization of the novel Xin protein to the adherens junction complex in cardiac and skeletal muscle during development","volume":"225","author":"HW Sinn","year":"2002","journal-title":"Dev Dyn"},{"key":"pcbi.1008798.ref034","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1016\/j.yexcr.2006.03.015","article-title":"Unusual splicing events result in distinct Xin isoforms that associate differentially with filamin c and Mena\/VASP","volume":"312","author":"PFM van der Ven","year":"2006","journal-title":"Exp Cell Res"},{"key":"pcbi.1008798.ref035","doi-asserted-by":"crossref","first-page":"3215","DOI":"10.1091\/mbc.e13-04-0202","article-title":"Identification of Xin-repeat proteins as novel ligands of the SH3 domains of nebulin and nebulette and analysis of their interaction during myofibril formation and remodeling","volume":"24","author":"S Eulitz","year":"2013","journal-title":"Mol Biol Cell"},{"key":"pcbi.1008798.ref036","doi-asserted-by":"crossref","first-page":"3578","DOI":"10.1242\/jcs.152157","article-title":"Aciculin interacts with filamin C and Xin and is essential for myofibril assembly, remodeling and maintenance","volume":"127","author":"S Molt","year":"2014","journal-title":"J Cell Sci"},{"key":"pcbi.1008798.ref037","doi-asserted-by":"crossref","first-page":"48102","DOI":"10.1039\/C7RA08030A","article-title":"Structural predictions for curli amyloid fibril subunits CsgA and CsgB","volume":"7","author":"EP DeBenedictis","year":"2017","journal-title":"RSC Adv"},{"key":"pcbi.1008798.ref038","doi-asserted-by":"crossref","unstructured":"Perov S, Lidor O, Salinas N, Golan N, Tayeb-Fligelman E, Deshmukh M, et al. Structural Insights into Curli CsgA Cross-\u03b2 Fibril Architecture Inspired Repurposing of Anti-amyloid Compounds as Anti-biofilm Agents. doi: 10.1101\/493668","DOI":"10.1101\/493668"},{"key":"pcbi.1008798.ref039","doi-asserted-by":"crossref","first-page":"W402","DOI":"10.1093\/nar\/gky360","article-title":"RepeatsDB-lite: a web server for unit annotation of tandem repeat proteins","volume":"46","author":"L Hirsh","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"pcbi.1008798.ref040","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1093\/bioinformatics\/btl158","article-title":"Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences","author":"W Li","year":"2006","journal-title":"Bioinformatics"},{"key":"pcbi.1008798.ref041","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/nmeth.1818","article-title":"HHblits: lightning-fast iterative protein sequence searching by HMM-HMM alignment","author":"M Remmert","year":"2012","journal-title":"Nature Methods"},{"key":"pcbi.1008798.ref042","doi-asserted-by":"crossref","first-page":"D170","DOI":"10.1093\/nar\/gkw1081","article-title":"Uniclust databases of clustered and deeply annotated protein sequences and alignments","volume":"45","author":"M Mirdita","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"pcbi.1008798.ref043","doi-asserted-by":"crossref","first-page":"e75","DOI":"10.1002\/cpbi.75","article-title":"Using PconsC4 and PconsFold2 to Predict Protein Structure.","author":"C Bassot","year":"2019","journal-title":"Curr Protoc Bioinformatics"},{"key":"pcbi.1008798.ref044","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1093\/bioinformatics\/16.4.404","article-title":"The PSIPRED protein structure prediction server","author":"LJ McGuffin","year":"2000","journal-title":"Bioinformatics"},{"key":"pcbi.1008798.ref045","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1002\/prot.25779","article-title":"Prediction of interresidue contacts with DeepMetaPSICOV in CASP13","volume":"87","author":"SM Kandathil","year":"2019","journal-title":"Proteins"},{"key":"pcbi.1008798.ref046","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1093\/nar\/gki524","article-title":"TM-align: a protein structure alignment algorithm based on the TM-score","volume":"33","author":"Y Zhang","year":"2005","journal-title":"Nucleic Acids Res"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1008798","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,4,27]],"date-time":"2021-04-27T00:00:00Z","timestamp":1619481600000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1008798","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T06:04:53Z","timestamp":1698905093000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1008798"}},"subtitle":[],"editor":[{"given":"Johannes","family":"Soeding","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,4,15]]},"references-count":46,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2021,4,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1008798","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pcbi.1008798","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,15]]}}}