{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T22:50:38Z","timestamp":1783983038805,"version":"3.55.0"},"reference-count":18,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T00:00:00Z","timestamp":1704412800000},"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"}]},{"name":"Science and Education for Smart Growth Operational Program","award":["OC\/EFSA\/GMO\/2019\/02"],"award-info":[{"award-number":["OC\/EFSA\/GMO\/2019\/02"]}]},{"name":"Science and Education for Smart Growth Operational Program","award":["BG05M2OP001-1.001-0003"],"award-info":[{"award-number":["BG05M2OP001-1.001-0003"]}]},{"name":"European Structural and Investment funds","award":["OC\/EFSA\/GMO\/2019\/02"],"award-info":[{"award-number":["OC\/EFSA\/GMO\/2019\/02"]}]},{"name":"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>Peptide\u2013protein interactions form a cornerstone in molecular biology, governing cellular signaling, structure, and enzymatic activities in living organisms. Improving computational models and experimental techniques to describe and predict these interactions remains an ongoing area of research. Here, we present a computational method for peptide\u2013protein interactions\u2019 description and prediction based on leveraged amino acid frequencies within specific binding cores. Utilizing normalized frequencies, we construct quantitative matrices (QMs), termed \u2018logo models\u2019 derived from sequence logos. The method was developed to predict peptide binding to HLA-DQ2.5 and HLA-DQ8.1 proteins associated with susceptibility to celiac disease. The models were validated by more than 17,000 peptides demonstrating their efficacy in discriminating between binding and non-binding peptides. The logo method could be applied to diverse peptide\u2013protein interactions, offering a versatile tool for predictive analysis in molecular binding studies.<\/jats:p>","DOI":"10.3390\/molecules29020284","type":"journal-article","created":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T03:43:00Z","timestamp":1704426180000},"page":"284","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Modeling Peptide\u2013Protein Interactions by a Logo-Based Method: Application in Peptide\u2013HLA Binding Predictions"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1469-1768","authenticated-orcid":false,"given":"Irini","family":"Doytchinova","sequence":"first","affiliation":[{"name":"Faculty of Pharmacy, Medical University of Sofia, 1000 Sofia, Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9761-0355","authenticated-orcid":false,"given":"Mariyana","family":"Atanasova","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":"F. Javier","family":"Moreno","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n en Ciencias de la Alimentaci\u00f3n (CIAL), CSIC-UAM, CEI (UAM+CSIC), Nicol\u00e1s Cabrera, 9, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4007-5715","authenticated-orcid":false,"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\/0000-0003-4838-312X","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"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5867","DOI":"10.1039\/C7OB01092C","article-title":"Self-assembly of bioactive peptides, peptide conjugates, and peptide mimetic materials","volume":"15","author":"Hamley","year":"2017","journal-title":"Org. Biomol. Chem."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.drudis.2014.10.003","article-title":"Peptide therapeutics: Current status and future directions","volume":"20","author":"Fosgerau","year":"2015","journal-title":"Drug Discov. Today"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1038\/nature10317","article-title":"Molecular chaperones in protein folding and proteostasis","volume":"475","author":"Hartl","year":"2011","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.tips.2023.04.003","article-title":"Recent advances in the development of therapeutic peptides","volume":"44","author":"Fetse","year":"2023","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/pro.3022","article-title":"How cryo-electron microscopy and X-ray crystallography complement each other","volume":"26","author":"Wang","year":"2017","journal-title":"Protein Sci."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Perez, J.J., Perez, R.A., and Perez, A. (2021). Computational Modeling as a Tool to Investigate PPI: From Drug Design to Tissue Engineering. Front. Mol. Biosci., 8.","DOI":"10.3389\/fmolb.2021.681617"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6097","DOI":"10.1093\/nar\/18.20.6097","article-title":"Sequence Logos: A New Way to Display Consensus Sequences","volume":"18","author":"Schneider","year":"1990","journal-title":"Nucleic Acids Res."},{"key":"ref_8","first-page":"41","article-title":"Comprehensive, quantitative mapping of T cell epitopes in gluten in celiac disease","volume":"2","author":"Stewart","year":"2010","journal-title":"Sci. Transl. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"207","DOI":"10.2174\/187153012800493549","article-title":"Repertoire of gluten peptides active in celiac disease patients: Perspectives for translational therapeutic applications","volume":"12","author":"Camarca","year":"2012","journal-title":"Endocr. Metab. Immune Disord. Drug Targets"},{"key":"ref_10","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_11","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_12","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_13","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_14","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_15","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_16","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_17","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_18","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."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/2\/284\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:40:21Z","timestamp":1760103621000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/2\/284"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,5]]},"references-count":18,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,1]]}},"alternative-id":["molecules29020284"],"URL":"https:\/\/doi.org\/10.3390\/molecules29020284","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,5]]}}}