{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T16:36:53Z","timestamp":1785343013273,"version":"3.55.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T00:00:00Z","timestamp":1691107200000},"content-version":"vor","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of University and Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Coiled-coil domains (CCD) are widespread in all organisms and perform several crucial functions. Given their relevance, the computational detection of CCD is very important for protein functional annotation. State-of-the-art prediction methods include the precise identification of CCD boundaries, the annotation of the typical heptad repeat pattern along the coiled-coil helices as well as the prediction of the oligomerization state.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In this article, we describe CoCoNat, a novel method for predicting coiled-coil helix boundaries, residue-level register annotation, and oligomerization state. Our method encodes sequences with the combination of two state-of-the-art protein language models and implements a three-step deep learning procedure concatenated with a Grammatical-Restrained Hidden Conditional Random Field for CCD identification and refinement. A final neural network predicts the oligomerization state. When tested on a blind test set routinely adopted, CoCoNat obtains a performance superior to the current state-of-the-art both for residue-level and segment-level CCD. CoCoNat significantly outperforms the most recent state-of-the-art methods on register annotation and prediction of oligomerization states.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>CoCoNat web server is available at https:\/\/coconat.biocomp.unibo.it. Standalone version is available on GitHub at https:\/\/github.com\/BolognaBiocomp\/coconat.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btad495","type":"journal-article","created":{"date-parts":[[2023,8,3]],"date-time":"2023-08-03T16:17:29Z","timestamp":1691079449000},"source":"Crossref","is-referenced-by-count":40,"title":["CoCoNat: a novel method based on deep learning for coiled-coil prediction"],"prefix":"10.1093","volume":"39","author":[{"given":"Giovanni","family":"Madeo","sequence":"first","affiliation":[{"name":"Biocomputing Group, Department of Pharmacy and Biotechnology, University of Bologna , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7359-0633","authenticated-orcid":false,"given":"Castrense","family":"Savojardo","sequence":"additional","affiliation":[{"name":"Biocomputing Group, Department of Pharmacy and Biotechnology, University of Bologna , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5479-1723","authenticated-orcid":false,"given":"Matteo","family":"Manfredi","sequence":"additional","affiliation":[{"name":"Biocomputing Group, Department of Pharmacy and Biotechnology, University of Bologna , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0274-5669","authenticated-orcid":false,"given":"Pier Luigi","family":"Martelli","sequence":"additional","affiliation":[{"name":"Biocomputing Group, Department of Pharmacy and Biotechnology, University of Bologna , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7462-7039","authenticated-orcid":false,"given":"Rita","family":"Casadio","sequence":"additional","affiliation":[{"name":"Biocomputing Group, Department of Pharmacy and Biotechnology, University of Bologna , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,8,4]]},"reference":[{"key":"2023081420341619100_btad495-B1","doi-asserted-by":"crossref","first-page":"2757","DOI":"10.1093\/bioinformatics\/btp539","article-title":"CCHMM_PROF: a HMM-based coiled-coil predictor with evolutionary information","volume":"25","author":"Bartoli","year":"2009","journal-title":"Bioinformatics"},{"key":"2023081420341619100_btad495-B2","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1038\/170882b0","article-title":"Is alpha-keratin a coiled coil?","volume":"170","author":"Crick","year":"1952","journal-title":"Nature"},{"key":"2023081420341619100_btad495-B3","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1107\/S0365110X53001952","article-title":"The Fourier transform of a coiled-coil","volume":"6","author":"Crick","year":"1953","journal-title":"Acta Cryst"},{"key":"2023081420341619100_btad495-B4","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1107\/S0365110X53001964","article-title":"The packing of \u03b1-helices: simple coiled-coils","volume":"6","author":"Crick","year":"1953","journal-title":"Acta Cryst"},{"key":"2023081420341619100_btad495-B5","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1093\/bioinformatics\/18.4.617","article-title":"An HMM model for coiled-coil domains and a comparison with PSSM-based predictions","volume":"18","author":"Delorenzi","year":"2002","journal-title":"Bioinformatics"},{"key":"2023081420341619100_btad495-B6","doi-asserted-by":"crossref","first-page":"7112","DOI":"10.1109\/TPAMI.2021.3095381","article-title":"ProtTrans: Toward understanding the language of life through self-supervised learning","volume":"44","author":"Elnaggar","year":"2022","journal-title":"IEEE Trans Pattern Anal Mach Intell"},{"key":"2023081420341619100_btad495-B7","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1748-7188-4-13","article-title":"Grammatical-Restrained Hidden Conditional Random Fields for Bioinformatics applications","volume":"4","author":"Fariselli","year":"2009","journal-title":"Algorithms Mol Biol"},{"key":"2023081420341619100_btad495-B8","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1093\/bioinformatics\/btab744","article-title":"CoCoPRED: coiled-coil protein structural feature prediction from amino acid sequence using deep neural networks","volume":"38","author":"Feng","year":"2022","journal-title":"Bioinformatics"},{"key":"2023081420341619100_btad495-B9","doi-asserted-by":"crossref","first-page":"D304","DOI":"10.1093\/nar\/gkt1240","article-title":"SCOPe: structural classification of proteins\u2014extended, integrating SCOP and ASTRAL data and classification of new structures","volume":"42","author":"Fox","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"2023081420341619100_btad495-B10","doi-asserted-by":"crossref","first-page":"W239","DOI":"10.1093\/nar\/gki405","article-title":"REPPER\u2013repeats and their periodicities in fibrous proteins","volume":"33","author":"Gruber","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"2023081420341619100_btad495-B11","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1162\/neco.1997.9.8.1735","article-title":"Long short-term memory","volume":"9","author":"Hochreiter","year":"1997","journal-title":"Neural Comput"},{"key":"2023081420341619100_btad495-B12","author":"Kingma","year":"2017"},{"key":"2023081420341619100_btad495-B13","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1162\/neco.1989.1.4.541","article-title":"Backpropagation applied to handwritten zip code recognition","volume":"1","author":"LeCun","year":"1989","journal-title":"Neural Comput"},{"key":"2023081420341619100_btad495-B14","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1093\/bib\/bbv047","article-title":"Critical evaluation of in silico methods for prediction of coiled-coil domains in proteins","volume":"17","author":"Li","year":"2016","journal-title":"Brief Bioinform"},{"key":"2023081420341619100_btad495-B15","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1126\/science.ade2574","article-title":"Evolutionary-scale prediction of atomic-level protein structure with a language model","volume":"379","author":"Lin","year":"2023","journal-title":"Science"},{"key":"2023081420341619100_btad495-B16","doi-asserted-by":"crossref","first-page":"2790","DOI":"10.1093\/bioinformatics\/bty1062","article-title":"DeepCoil: a fast and accurate prediction of coiled-coil domains in protein sequences","volume":"35","author":"Ludwiczak","year":"2019","journal-title":"Bioinformatics"},{"key":"2023081420341619100_btad495-B17","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1126\/science.252.5009.1162","article-title":"Predicting coiled coils from protein sequences","volume":"252","author":"Lupas","year":"1991","journal-title":"Science"},{"key":"2023081420341619100_btad495-B18","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.tibs.2016.10.007","article-title":"Coiled coils - a model system for the 21st century","volume":"42","author":"Lupas","year":"2017","journal-title":"Trends Biochem Sci"},{"key":"2023081420341619100_btad495-B19","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0065-3233(05)70003-6","volume-title":"Advances in Protein Chemistry: Fibrous Proteins: Coiled-Coils, Collagen and Elastomers","author":"Lupas","year":"2005"},{"key":"2023081420341619100_btad495-B20","volume-title":"Fibrous Proteins: Structures and Mechanisms. Subcellular Biochemistry","author":"Lupas"},{"key":"2023081420341619100_btad495-B21","doi-asserted-by":"crossref","first-page":"166729","DOI":"10.1016\/j.jmb.2020.166729","article-title":"BetAware-Deep: an accurate web server for discrimination and topology prediction of prokaryotic transmembrane \u03b2-barrel proteins","volume":"433","author":"Madeo","year":"2021","journal-title":"J Mol Biol"},{"key":"2023081420341619100_btad495-B22","doi-asserted-by":"crossref","first-page":"M110.004994","DOI":"10.1074\/mcp.M110.004994","article-title":"Complex networks govern coiled-coil oligomerization\u2013predicting and profiling by means of a machine learning approach","volume":"10","author":"Mahrenholz","year":"2011","journal-title":"Mol Cell Proteomics"},{"key":"2023081420341619100_btad495-B23","doi-asserted-by":"crossref","first-page":"5168","DOI":"10.1093\/bioinformatics\/btac678","article-title":"E-SNPs&GO: embedding of protein sequence and function improves the annotation of human pathogenic variants","volume":"38","author":"Manfredi","year":"2022","journal-title":"Bioinformatics"},{"key":"2023081420341619100_btad495-B24","doi-asserted-by":"crossref","first-page":"167963","DOI":"10.1016\/j.jmb.2023.167963","article-title":"ISPRED-SEQ: deep neural networks and embeddings for predicting interaction sites in protein sequences","volume":"435","author":"Manfredi","year":"2023","journal-title":"J Mol Biol"},{"key":"2023081420341619100_btad495-B25","doi-asserted-by":"crossref","first-page":"5368","DOI":"10.1093\/bioinformatics\/btaa1041","article-title":"A library of coiled-coil domains: from regular bundles to peculiar twists","volume":"36","author":"Szczepaniak","year":"2020","journal-title":"Bioinformatics"},{"key":"2023081420341619100_btad495-B26","doi-asserted-by":"crossref","first-page":"D315","DOI":"10.1093\/nar\/gkn675","article-title":"CC+: a relational database of coiled-coil structures","volume":"37","author":"Testa","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"2023081420341619100_btad495-B27","doi-asserted-by":"crossref","first-page":"e23519","DOI":"10.1371\/journal.pone.0023519","article-title":"Multicoil2: predicting coiled coils and their oligomerization states from sequence in the twilight zone","volume":"6","author":"Trigg","year":"2011","journal-title":"PLoS One"},{"key":"2023081420341619100_btad495-B28","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1002\/bies.201600062","article-title":"Coiled-coils: the long and short of it","volume":"38","author":"Truebestein","year":"2016","journal-title":"Bioessays"},{"key":"2023081420341619100_btad495-B29","first-page":"2579","article-title":"Visualizing data using t-SNE","volume":"9","author":"van der Maaten","year":"2008","journal-title":"J Mach Learn Res"},{"key":"2023081420341619100_btad495-B30","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1093\/bioinformatics\/bts648","article-title":"LOGICOIL\u2014multi-state prediction of coiled-coil oligomeric state","volume":"29","author":"Vincent","year":"2013","journal-title":"Bioinformatics"},{"key":"2023081420341619100_btad495-B31","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1006\/jmbi.2001.4545","article-title":"Socket: a program for identifying and analysing coiled-coil motifs within protein structures","volume":"307","author":"Walshaw","year":"2001","journal-title":"J Mol Biol"},{"key":"2023081420341619100_btad495-B32","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1038\/289366a0","article-title":"Structure of the haemagglutinin membrane glycoprotein of influenza virus at 3 a resolution","volume":"289","author":"Wilson","year":"1981","journal-title":"Nature"},{"key":"2023081420341619100_btad495-B33","doi-asserted-by":"crossref","first-page":"104579","DOI":"10.1016\/j.jbc.2023.104579","article-title":"Understanding a protein fold: the physics, chemistry, and biology of \u03b1-helical coiled coils","volume":"299","author":"Woolfson","year":"2023","journal-title":"J Biol Chem"},{"key":"2023081420341619100_btad495-B34","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1002\/(SICI)1097-0134(19990201)34:2<220::AID-PROT7>3.0.CO;2-K","article-title":"A modified definition of SOV, a segment-based measure for protein secondary structure prediction assessment","volume":"34","author":"Zemla","year":"1999","journal-title":"Proteins"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btad495\/51038865\/btad495.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/39\/8\/btad495\/51111770\/btad495.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/39\/8\/btad495\/51111770\/btad495.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T16:59:37Z","timestamp":1692032377000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/doi\/10.1093\/bioinformatics\/btad495\/7237258"}},"subtitle":[],"editor":[{"given":"Arne","family":"Elofsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,8,1]]},"references-count":34,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2023,8,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btad495","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.05.08.539816","asserted-by":"object"}]},"ISSN":["1367-4811"],"issn-type":[{"value":"1367-4811","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,8,1]]},"published":{"date-parts":[[2023,8,1]]},"article-number":"btad495"}}