{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T20:33:30Z","timestamp":1784147610310,"version":"3.55.0"},"reference-count":43,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,12,26]],"date-time":"2023-12-26T00:00:00Z","timestamp":1703548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014803","name":"European Food Safety Authority","doi-asserted-by":"publisher","award":["OC\/EFSA\/GMO\/2019\/02"],"award-info":[{"award-number":["OC\/EFSA\/GMO\/2019\/02"]}],"id":[{"id":"10.13039\/100014803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014803","name":"European Food Safety Authority","doi-asserted-by":"publisher","award":["BG05M2OP001-1.001-0003"],"award-info":[{"award-number":["BG05M2OP001-1.001-0003"]}],"id":[{"id":"10.13039\/100014803","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014803","name":"European Food Safety Authority","doi-asserted-by":"publisher","award":["BG05M2OP001-1.001-0003"],"award-info":[{"award-number":["BG05M2OP001-1.001-0003"]}],"id":[{"id":"10.13039\/100014803","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science and Education for Smart Growth Operational Pro-gram","award":["OC\/EFSA\/GMO\/2019\/02"],"award-info":[{"award-number":["OC\/EFSA\/GMO\/2019\/02"]}]},{"name":"Science and Education for Smart Growth Operational Pro-gram","award":["BG05M2OP001-1.001-0003"],"award-info":[{"award-number":["BG05M2OP001-1.001-0003"]}]},{"name":"Science and Education for Smart Growth Operational Pro-gram","award":["BG05M2OP001-1.001-0003"],"award-info":[{"award-number":["BG05M2OP001-1.001-0003"]}]},{"name":"European Union through the European Structural and Investment funds","award":["OC\/EFSA\/GMO\/2019\/02"],"award-info":[{"award-number":["OC\/EFSA\/GMO\/2019\/02"]}]},{"name":"European Union through the European Structural and Investment funds","award":["BG05M2OP001-1.001-0003"],"award-info":[{"award-number":["BG05M2OP001-1.001-0003"]}]},{"name":"European Union through the European Structural and Investment funds","award":["BG05M2OP001-1.001-0003"],"award-info":[{"award-number":["BG05M2OP001-1.001-0003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Human leukocyte antigens (HLAs) are pivotal in antigen processing, presenting to CD4+ T cells, and are linked to autoimmune disease susceptibility. In celiac disease, HLA-DQ2.5 and HLA-DQ8.1 bind gluten peptides on APCs, some recognized by CD4+ T cells, prompting inflammation and tissue damage. While extensively studied experimentally, these alleles lack comprehensive in silico analysis. To explore peptide\u2013HLA preferences, we used molecular docking on peptide libraries, deriving quantitative matrices (QMs) for evaluating amino acids at nine-residue peptide binding cores. Our findings tie specific residue preferences to peptide backbone conformations. Validating QMs on known binders and non-binders showed strong predictive power (89\u201394% accuracy). These QMs excel in screening protein libraries, even whole proteomes, notably reducing time and costs for celiac disease risk assessment in novel proteins. This computational approach aligns with European Food Safety Authority guidance, promising efficient screening for potential celiac disease triggers.<\/jats:p>","DOI":"10.3390\/molecules29010138","type":"journal-article","created":{"date-parts":[[2023,12,26]],"date-time":"2023-12-26T05:19:07Z","timestamp":1703567947000},"page":"138","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Assessment of Novel Proteins Triggering Celiac Disease via Docking-Based Approach"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9761-0355","authenticated-orcid":false,"given":"Mariyana","family":"Atanasova","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4838-312X","authenticated-orcid":false,"given":"Ivan","family":"Dimitrov","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Fernandez","sequence":"additional","affiliation":[{"name":"European Food Safety Authority, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7637-9542","authenticated-orcid":false,"given":"Javier","family":"Moreno","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Ciencias de la Alimentaci\u00f3n (CIAL), Consejo Superior de Investigaciones Cientificas-Universidad Autonoma de Madrid (CSIC-UAM), Campus of Interntional Excellence\u2014CEI (UAM+CSIC), Nicol\u00e1s Cabrera, 9, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frits","family":"Koning","sequence":"additional","affiliation":[{"name":"Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, 2333 ZA Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1469-1768","authenticated-orcid":false,"given":"Irini","family":"Doytchinova","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Patronov, A., and Doytchinova, I. (2013). T-cell epitope vaccine design by immunoinformatics. Open Biol., 3.","DOI":"10.1098\/rsob.120139"},{"key":"ref_2","first-page":"D948","article-title":"IPD-IMGT\/HLA database","volume":"48","author":"Robinson","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/ng.1076","article-title":"Five amino acids in three HLA proteins explain most of the association between MHC and seropositive rheumatoid arthritis","volume":"44","author":"Raychaudhuri","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"692041","DOI":"10.3389\/fimmu.2021.692041","article-title":"In rheumatoid arthritis patients, HLA-DRB1*04:01 and rheumatoid nodules are associated with ACPA to a particular fibrin epitope","volume":"12","author":"Larid","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1177\/0961203308101955","article-title":"Molecular analysis of HLA-DRB1 allelic associations with systemic lupus erythematous and lupus nephritis in Taiwan","volume":"18","author":"Pan","year":"2009","journal-title":"Lupus"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1016\/j.ajhg.2012.08.026","article-title":"Unraveling multiple MHC gene associations with systemic lupus erythematosus: Model choice indicates a role for HLA alleles and non-HLA genes in Europeans","volume":"91","author":"Morris","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5110","DOI":"10.1038\/s41467-021-25404-x","article-title":"T cell receptor recognition of hybrid insulin peptides bound to HLA-DQ8","volume":"12","author":"Tran","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"8821","DOI":"10.1038\/s41598-021-86229-8","article-title":"Nine residues in HLA-DQ molecules determine with susceptibility and resistance to type 1 diabetes among young children in Sweden","volume":"11","author":"Zhao","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1046\/j.1399-0039.2003.00160.x","article-title":"Chronic beryllium disease: Immune-mediated destruction with implications for organ-specific autoimmunity","volume":"62","author":"Fontenot","year":"2003","journal-title":"Tissue Antigens"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.immuni.2007.05.015","article-title":"A structural and immunological basis for the role of human leukocyte antigen DQ8 in celiac disease","volume":"27","author":"Henderson","year":"2007","journal-title":"Immunity"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1590\/S0102-67202015000300009","article-title":"The prevalence of HLA DQ2 and DQ8 in patients with celiac disease, in family and in general population","volume":"28","author":"Cecilio","year":"2015","journal-title":"Arq. Bras. De Cir. Dig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1136\/gutjnl-2011-301346","article-title":"The Oslo definitions for coeliac disease and related terms","volume":"62","author":"Ludvigsson","year":"2013","journal-title":"Gut"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1172\/JCI30253","article-title":"Celiac Disease: Pathogenesis of a Model Immunogenetic Disease","volume":"117","author":"Kagnoff","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"10331","DOI":"10.3748\/wjg.v21.i23.7110","article-title":"Diagnosis of gluten related disorders: Celiac disease, wheat allergy and non-celiac gluten sensitivity","volume":"21","author":"Elli","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"h4347","DOI":"10.1136\/bmj.h4347","article-title":"Celiac disease and non-celiac gluten sensitivity","volume":"351","author":"Lebwohl","year":"2015","journal-title":"BMJ"},{"key":"ref_16","first-page":"e39004","article-title":"Novel Therapies for Celiac Disease: A Clinical Review Article","volume":"15","author":"Ghazanfar","year":"2023","journal-title":"Cureus"},{"key":"ref_17","first-page":"D783","article-title":"Allele frequency net database (AFND) 2020 update: Gold-standard data classification, open access genotype data and new query tools","volume":"48","author":"McCabe","year":"2020","journal-title":"Nucleic Acid Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"S33","DOI":"10.1053\/j.gastro.2005.02.013","article-title":"Genetic Testing: Who Should Do the Testing and What Is the Role of Genetic Testing in the Setting of Celiac Disease?","volume":"128","author":"Liu","year":"2005","journal-title":"Gastroenterology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1093\/intimm\/12.8.1157","article-title":"Structure of Celiac Disease-Associated HLA-DQ8 and Non-Associated HLA-DQ9 Alleles in Complex with Two Disease-Specific Epitopes","volume":"12","author":"Moustakas","year":"2000","journal-title":"Int. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1007\/s002510050309","article-title":"Unique Peptide Binding Characteristics of the Disease-Associated DQ(\u03b11*0501, \u03b21*0201) vs the Non-Disease-Associated DQ(\u03b11*0201, \u03b21*0202) Molecule","volume":"46","author":"Kooy","year":"1997","journal-title":"Immunogenetics"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/S0022-2836(02)00366-2","article-title":"Human Genome Search in Celiac Disease: Mutated Gliadin T-Cell-like Epitope in Two Human Proteins Promotes T-Cell Activation","volume":"319","author":"Kumar","year":"2002","journal-title":"J. Mol. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.jmgm.2004.12.002","article-title":"Modelling of HLA-DQ2 and Its Interaction with Gluten Peptides to Explain Molecular Recognition in Celiac Disease","volume":"23","author":"Costantini","year":"2005","journal-title":"J. Mol. Graph. Model."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1053\/j.gastro.2007.06.023","article-title":"Transamidation of Wheat Flour Inhibits the Response to Gliadin of Intestinal T Cells in Celiac Disease","volume":"133","author":"Gianfrani","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2764","DOI":"10.1002\/eji.1830261132","article-title":"The peptide binding motif of the disease associated HLA-DQ (alpha 1* 0501, beta 1* 0201) molecule","volume":"26","author":"Vartdal","year":"1996","journal-title":"Eur. J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.reval.2018.10.003","article-title":"Docking of Peptide Candidates to HLA-DQ2 and HLA-DQ8 Basket as a Tool for Predicting Potential Immunotoxic Peptides toward Celiac Diseased People","volume":"58","author":"Barre","year":"2018","journal-title":"Rev. Fr. Allergol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3063","DOI":"10.1073\/pnas.1914308117","article-title":"A Molecular Basis for the T Cell Response in HLA-DQ2.2 Mediated Celiac Disease","volume":"117","author":"Ting","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1093\/protein\/gzt018","article-title":"EpiDOCK: A Molecular Docking-Based Tool for MHC Class II Binding Prediction","volume":"26","author":"Atanasova","year":"2013","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1074\/jbc.RA118.005736","article-title":"Discriminative T-cell receptor recognition of highly homologous HLA-DQ2-bound gluten epitopes","volume":"294","author":"Ciacchi","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1007\/BF02602553","article-title":"Peptide binding characteristics of the coeliac disease-associated DQ (\u03b11*0501, \u03b21*0201) molecule","volume":"44","author":"Kooy","year":"1996","journal-title":"Immunogenetics"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1111\/imm.13279","article-title":"Comparison of HLA ligand elution data and binding predictions reveals varying prediction performance for the multiple motifs recognized by HLA-DQ2.5","volume":"162","author":"Sidney","year":"2021","journal-title":"Immunology"},{"key":"ref_31","unstructured":"(2023, November 28). Commission Implementing Regulation (EU) No 503\/2013 of 3 April 2013 on applications for authorisation of genetically modified food and feed in accordance with Regulation (EC) No 1829\/2003 of the European Parliament and of the Council and amending Commission Regulations (EC) No 641\/2004 and (EC) No 1981\/2006. OJ L157, 8.6.2013. Available online: https:\/\/eur-lex.europa.eu\/LexUriServ\/LexUriServ.do?uri=OJ:L:2013:157:0001:0048:EN:PDF."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"EFSA Panel on Genetically Modified Organisms (GMO), Naegeli, H., Birch, A.N., Casacuberta, J., De Schrijver, A., Gralak, M.A., Guerche, P., Jones, H., Manachini, B., and Mess\u00e9an, A. (2017). Guidance on allergenicity assessment of genetically modified plants. EFSA J., 15, e04862.","DOI":"10.2903\/j.efsa.2017.4862"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4189","DOI":"10.4049\/jimmunol.1001006","article-title":"Divergent motifs but overlapping binding repertoires of six HLA-DQ molecules frequently expressed in the worldwide human population","volume":"185","author":"Sidney","year":"2010","journal-title":"J. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3268","DOI":"10.4049\/jimmunol.180.5.3268","article-title":"Large-scale characterization of natural ligands explains the unique gluten-binding properties of HLA-DQ2","volume":"180","author":"Stepniak","year":"2008","journal-title":"J. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2468","DOI":"10.4049\/jimmunol.155.5.2468","article-title":"HLA-DQ polymorphisms are highly selective for peptide binding interactions","volume":"155","author":"Kwok","year":"1995","journal-title":"J. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1084\/jem.183.3.1253","article-title":"HLA-DQB1 codon 57 is critical for peptide binding and recognition","volume":"183","author":"Kwok","year":"1996","journal-title":"J. Exp. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.4049\/jimmunol.156.6.2171","article-title":"Allele-specific motifs characterize HLA-DQ interactions with a diabetes-associated peptide derived from glutamic acid decarboxylase","volume":"156","author":"Kwok","year":"1996","journal-title":"J. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1111\/j.1365-2567.2012.03579.x","article-title":"Characterizing the binding motifs of 11 common human HLA-DP and HLA-DQ molecules using NNAlign","volume":"136","author":"Andreatta","year":"2012","journal-title":"Immunology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s00251-014-0819-9","article-title":"Different binding motifs of the celiac disease-associated HLA molecules DQ2.5, DQ2.2, and DQ7.5 revealed by relative quantitative proteomics of endogenous peptide repertoires","volume":"67","author":"Bergseng","year":"2015","journal-title":"Immunogenetics"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J. Comput. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3891","DOI":"10.1021\/acs.jcim.1c00203","article-title":"AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings","volume":"61","author":"Eberhardt","year":"2021","journal-title":"J. Chem. Inf. Model."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1002\/jcc.20290","article-title":"The Amber biomolecular simulation programs","volume":"26","author":"Case","year":"2005","journal-title":"J. Comput. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.1021\/ct400341p","article-title":"PTRAJ and CPPTRAJ: Sofware for Processing and Analysis of Molecular Dynamics Trajectory Data","volume":"9","author":"Roe","year":"2013","journal-title":"J. Chem. Theory Comput."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/1\/138\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:42:06Z","timestamp":1760132526000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/1\/138"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,26]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["molecules29010138"],"URL":"https:\/\/doi.org\/10.3390\/molecules29010138","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,26]]}}}