{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T12:45:02Z","timestamp":1772196302157,"version":"3.50.1"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: While processing of MHC class II antigens for presentation to helper T-cells is essential for normal immune response, it is also implicated in the pathogenesis of autoimmune disorders and hypersensitivity reactions. Sequence-based computational techniques for predicting HLA-DQ binding peptides have encountered limited success, with few prediction techniques developed using three-dimensional models.<\/jats:p>\n               <jats:p>Methods: We describe a structure-based prediction model for modeling peptide-DQ3.2\u03b2 complexes. We have developed a rapid and accurate protocol for docking candidate peptides into the DQ3.2\u03b2 receptor and a scoring function to discriminate binders from the background. The scoring function was rigorously trained, tested and validated using experimentally verified DQ3.2\u03b2 binding and non-binding peptides obtained from biochemical and functional studies.<\/jats:p>\n               <jats:p>Results: Our model predicts DQ3.2\u03b2 binding peptides with high accuracy [area under the receiver operating characteristic (ROC) curve AROC &amp;gt; 0.90], compared with experimental data. We investigated the binding patterns of DQ3.2\u03b2 peptides and illustrate that several registers exist within a candidate binding peptide. Further analysis reveals that peptides with multiple registers occur predominantly for high-affinity binders.<\/jats:p>\n               <jats:p>Contact: \u00a0shoba@els.mq.edu.au<\/jats:p>\n               <jats:p>Supplementary information: Supplementary data is available at Bioinformatics online.<\/jats:p>","DOI":"10.1093\/bioinformatics\/btl071","type":"journal-article","created":{"date-parts":[[2006,3,2]],"date-time":"2006-03-02T01:24:53Z","timestamp":1141262693000},"page":"1232-1238","source":"Crossref","is-referenced-by-count":31,"title":["Prediction of HLA-DQ3.2\u03b2 Ligands: evidence of multiple registers in class II binding peptides"],"prefix":"10.1093","volume":"22","author":[{"given":"Joo Chuan","family":"Tong","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore 1 \u00a0 1 \u00a0 \u00a0 8 Medical Drive, Singapore 117597, Singapore"},{"name":"Institute for Infocomm Research 2 \u00a0 2 \u00a0 \u00a0 21 Heng Mui Keng Terrace, Singapore 119613, Singapore"}]},{"given":"Guang Lan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute for Infocomm Research 2 \u00a0 2 \u00a0 \u00a0 21 Heng Mui Keng Terrace, Singapore 119613, Singapore"}]},{"given":"Tin Wee","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore 1 \u00a0 1 \u00a0 \u00a0 8 Medical Drive, Singapore 117597, Singapore"}]},{"given":"J. Thomas","family":"August","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, John Hopkins Medicine in Singapore 3 \u00a0 3 \u00a0 \u00a0 41 Science Park Road, Lobby C, The Gemini, Singapore 117610, Singapore"},{"name":"Department of Pharmacology and Molecular Sciences, John Hopkins University School of Medicine 4 \u00a0 4 \u00a0 \u00a0 Baltimore, MD, USA"}]},{"given":"Vladimir","family":"Brusic","sequence":"additional","affiliation":[{"name":"Institute for Infocomm Research 2 \u00a0 2 \u00a0 \u00a0 21 Heng Mui Keng Terrace, Singapore 119613, Singapore"},{"name":"Australian Centre for Plant Functional Genomics, School of Land and Food Sciences, and Institute for Molecular Bioscience, The University of Queensland 5 \u00a0 5 \u00a0 \u00a0 Brisbane 4072, Australia"}]},{"given":"Shoba","family":"Ranganathan","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biomolecular Sciences and Biotechnology Research Institute, Macquarie University 6 \u00a0 6 \u00a0 \u00a0 NSW 2109, Australia"},{"name":"Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore 1 \u00a0 1 \u00a0 \u00a0 8 Medical Drive, Singapore 117597, Singapore"}]}],"member":"286","published-online":{"date-parts":[[2006,3,1]]},"reference":[{"key":"2023012408202532700_b1","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1002\/jcc.540150503","article-title":"ICM\u2014a new method for protein modeling and design: Applications to docking and structure prediction from the distorted native conformation","volume":"15","author":"Abagyan","year":"1994","journal-title":"J. Comput. Chem."},{"key":"2023012408202532700_b2","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/jcph.1999.6233","article-title":"Ab initio folding of peptides by the optimal-bias Monte Carlo minimization procedure","volume":"151","author":"Abagyan","year":"1999","journal-title":"J. Comput. Phys."},{"key":"2023012408202532700_b3","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1002\/jcc.540160707","article-title":"The fast multipole boundary element method for molecular electrostatics: an optimal approach for large system","volume":"16","author":"Bharadwaj","year":"1995","journal-title":"J. Comput. Chem."},{"key":"2023012408202532700_b4","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1074\/mcp.M200054-MCP200","article-title":"A new method to estimate ligand\u2013receptor energetics","volume":"1","author":"Bock","year":"2002","journal-title":"Mol. Cell. Proteomics"},{"key":"2023012408202532700_b5","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1093\/bioinformatics\/14.2.121","article-title":"Prediction of MHC class II-binding peptides using an evolutionary algorithm and artificial neural network","volume":"14","author":"Brusic","year":"1998","journal-title":"Bioinformatics"},{"key":"2023012408202532700_b6","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1046\/j.1440-1711.2002.01088.x","article-title":"Prediction of promiscuous peptides that bind HLA class I molecules","volume":"80","author":"Brusic","year":"2002","journal-title":"Immunol. Cell Biol."},{"key":"2023012408202532700_b7","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.ymeth.2004.06.006","article-title":"Computational methods for prediction of T-cell epitopes\u2014a framework for modelling, testing, and applications","volume":"34","author":"Brusic","year":"2004","journal-title":"Methods"},{"key":"2023012408202532700_b8","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.4049\/jimmunol.158.4.1507","article-title":"MHC affinity, peptide liberation, T cell repertoire, and immunodominance all contribute to the paucity of MHC class I-restricted peptides recognized by antiviral CTL","volume":"158","author":"Deng","year":"1997","journal-title":"J. Immunol."},{"key":"2023012408202532700_b9","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1093\/bioinformatics\/btg312","article-title":"Towards the in silico identification of class II restricted T-cell epitopes: a partial least squares iterative self-consistent algorithm for affinity prediction","volume":"19","author":"Doytchinova","year":"2003","journal-title":"Bioinformatics"},{"key":"2023012408202532700_b10","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/ng0493-358","article-title":"HLA class II alleles and susceptibility and resistance to insulin dependent diabetes mellitus in Mexican-American families","volume":"3","author":"Erlich","year":"1993","journal-title":"Nat. Genet."},{"key":"2023012408202532700_b11","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1126\/science.1763324","article-title":"Linkage of faulty major histocompatibility complex class I to autoimmune diabetes","volume":"254","author":"Faustman","year":"1991","journal-title":"Science"},{"key":"2023012408202532700_b12","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.cellimm.2004.07.002","article-title":"Pathogenic human thyroglobulin peptides in HLA-DR3 transgenic mouse model of autoimmune thyroiditis","volume":"229","author":"Flynn","year":"2004","journal-title":"Cell. Immunol."},{"key":"2023012408202532700_b13","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1002\/pro.5560060617","article-title":"On the calculation of binding free energies using continuum methods: application to MHC class I protein-peptide interactions","volume":"6","author":"Froloff","year":"1997","journal-title":"Protein Sci."},{"key":"2023012408202532700_b14","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1093\/intimm\/9.6.905","article-title":"Use of eluted peptide sequence data to identify the binding characteristics of peptides to the insulin-dependent diabetes susceptibility allele HLA-DQ8 (DQ 3.2)","volume":"9","author":"Godkin","year":"1997","journal-title":"Int. Immunol."},{"key":"2023012408202532700_b15","doi-asserted-by":"crossref","first-page":"850","DOI":"10.4049\/jimmunol.161.2.850","article-title":"Use of complete eluted peptide sequence data from HLA-DR and \u2013DQ Molecules to Predict T Cell epitopes, and the influence of the nonbinding terminal regions of ligands in epitope selection","volume":"161","author":"Godkin","year":"1998","journal-title":"J. Immunol."},{"key":"2023012408202532700_b16","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.2337\/diabetes.48.10.1937","article-title":"Identification of peptides from autoantigens GAD65 and IA-2 that bind to HLA class II molecules predisposing to or protecting from type 1 diabetes","volume":"48","author":"Harfouch-Hammoud","year":"1999","journal-title":"Diabetes"},{"key":"2023012408202532700_b17","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/S0079-6107(96)00001-6","article-title":"Protein\u2013protein recognition","volume":"64","author":"Janin","year":"1995","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"2023012408202532700_b18","doi-asserted-by":"crossref","first-page":"787","DOI":"10.4049\/jimmunol.167.2.787","article-title":"Identification of new epitopes from four different tumor-associated antigens: recognition of naturally processed epitopes correlates with HLA-A*0201 binding affinity","volume":"167","author":"Keogh","year":"2001","journal-title":"J. Immunol."},{"key":"2023012408202532700_b19","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/71540","article-title":"Shaping of the autoreactive T-cell repertoire by a splice variant of self protein expressed in thymic epithelial cells","volume":"6","author":"Klein","year":"2000","journal-title":"Nat. Med."},{"key":"2023012408202532700_b20","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1172\/JCI11752","article-title":"Immunization with a HER-2\/neu helper peptide vaccine generates HER-2\/neu CD8 T-cell immunity in cancer patients","volume":"107","author":"Knutson","year":"2001","journal-title":"J. Clin. Invest."},{"key":"2023012408202532700_b21","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1006\/clim.2000.4931","article-title":"Immune response of HLA-DQ transgenic mice to house dust mite allergen p2: identification of HLA-DQ restricted minimal epitopes and critical residues","volume":"97","author":"Krco","year":"2000","journal-title":"Clin. Immunol."},{"key":"2023012408202532700_b22","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1006\/jmbi.1993.1619","article-title":"Affinity and specificity of serine endopeptidase-protein inhibitor interactions. Empirical free energy calculations based on X-ray crystallographic structures","volume":"234","author":"Krystek","year":"1993","journal-title":"J. Mol. Biol."},{"key":"2023012408202532700_b23","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1073\/pnas.86.3.1027","article-title":"Mutational analysis of the HLA-DQ3.2 insulin-dependent diabetes mellitus susceptibility gene","volume":"86","author":"Kwok","year":"1989","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2023012408202532700_b24","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/88694","article-title":"Structure of a human insulin peptide-HLA-DQ8 complex and susceptibility to type 1 diabetes","volume":"2","author":"Lee","year":"2001","journal-title":"Nat. Immunol."},{"key":"2023012408202532700_b25","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1006\/jmbi.2000.4198","article-title":"Structural basis for the binding of an immunodominant peptide from myelin basic protein in different registers by two HLA-DR2 proteins","volume":"304","author":"Li","year":"2000","journal-title":"J. Mol. Biol."},{"key":"2023012408202532700_b26","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1002\/1521-4141(200107)31:7<1989::AID-IMMU1989>3.0.CO;2-M","article-title":"A synthetic malaria vaccine elicits a potent CD8 (+) and CD4 (+) T lymphocyte immune response in humans. Implications for vaccination strategies","volume":"31","author":"Lopez","year":"2001","journal-title":"Eur. J. Immunol."},{"key":"2023012408202532700_b27","doi-asserted-by":"crossref","first-page":"942","DOI":"10.1093\/bioinformatics\/17.10.942","article-title":"Predicting class II MHC\/peptide multi-level binding with an iterative stepwise discriminant analysis meta-algorithm","volume":"17","author":"Mallios","year":"2001","journal-title":"Bioinformatics"},{"key":"2023012408202532700_b28","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1034\/j.1399-0039.2003.00062.x","article-title":"New allele frequency database","volume":"61","author":"Middleton","year":"2003","journal-title":"Tissue Antigens"},{"key":"2023012408202532700_b29","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":"2023012408202532700_b30","doi-asserted-by":"crossref","first-page":"3191","DOI":"10.4049\/jimmunol.156.9.3191","article-title":"HLA-DQ8 transgenic mice lacking endogenous class II molecules respond to house dust allergens: identification of antigenic epitopes","volume":"156","author":"Neeno","year":"1996","journal-title":"J. Immunol."},{"key":"2023012408202532700_b31","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.2337\/diab.47.8.1177","article-title":"Molecular basis for HLA-DQ associations with IDDM","volume":"47","author":"Nepom","year":"1998","journal-title":"Diabetes"},{"key":"2023012408202532700_b32","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1006\/jmbi.1997.0961","article-title":"Empirical free energy calculations: a blind test and further improvements to the method","volume":"268","author":"Novotny","year":"1997","journal-title":"J. Mol. Biol."},{"key":"2023012408202532700_b33","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s002510050595","article-title":"SYFPEITHI: database for MHC ligands and peptide motifs","volume":"50","author":"Rammensee","year":"1999","journal-title":"Immunogenetics"},{"key":"2023012408202532700_b34","article-title":"A practical guide to structure-based prediction of MHC binding peptides","volume-title":"Methods in Molecular Biology: Immunoinformatics: Predicting Immunogenicity in silico","author":"Ranganathan","year":"2005"},{"key":"2023012408202532700_b35","article-title":"Structural Immunoinformatics: Understanding MHC-peptide binding","volume-title":"Advances in Experimental Medicine Series\u2014Immunoinformatics: Opportunities and Challenges of Bridging Immunology with Computer and Information Sciences","author":"Ranganathan","year":"2005"},{"key":"2023012408202532700_b36","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/S0889-8529(01)00015-9","article-title":"The genetics of autoimmune polyendocrine syndrome type II","volume":"31","author":"Robles","year":"2002","journal-title":"Endocrinol. Metab. Clin. North. Am."},{"key":"2023012408202532700_b37","doi-asserted-by":"crossref","first-page":"4650","DOI":"10.1021\/jm9910775","article-title":"Predicting binding affinities of protein ligands from three-dimensional models: application to peptide binding to class I major histocompatibility proteins","volume":"42","author":"Rognan","year":"1999","journal-title":"J. Med. Chem."},{"key":"2023012408202532700_b38","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1006\/jmbi.1993.1626","article-title":"Comparative protein modelling by satisfaction of spatial restraints","volume":"234","author":"Sali","year":"1993","journal-title":"J. Mol. Biol."},{"key":"2023012408202532700_b39","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/(SICI)1099-1352(199905\/06)12:3<177::AID-JMR451>3.0.CO;2-Z","article-title":"Prediction of the binding energy for small molecules, peptides and proteins","volume":"12","author":"Schapira","year":"1999","journal-title":"J. Mol. Recognit."},{"key":"2023012408202532700_b40","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1084\/jem.20022226","article-title":"Competition between two MHC binding registers in a single peptide processed from myelin basic protein influences tolerance and susceptibility to autoimmunity","volume":"197","author":"Seamons","year":"2003","journal-title":"J. Exp. Med."},{"key":"2023012408202532700_b41","doi-asserted-by":"crossref","first-page":"5098","DOI":"10.4049\/jimmunol.169.9.5098","article-title":"The HLA molecules DQA1*0501\/B1*0201 and DQA1*0301\/B1*0302 share an extensive overlap in peptide binding specificity","volume":"169","author":"Sidney","year":"2002","journal-title":"J. Immunol."},{"key":"2023012408202532700_b42","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1016\/0016-5085(93)90912-V","article-title":"HLA susceptibility genes in celiac disease: genetic mapping and role in pathogenesis [Erratum (1994) Gastroenterology 106 1133.]","volume":"105","author":"Sollid","year":"1993","journal-title":"Gastroenterology"},{"key":"2023012408202532700_b43","doi-asserted-by":"crossref","first-page":"3363","DOI":"10.4049\/jimmunol.160.7.3363","article-title":"Several common HLA-DR types share largely overlapping peptide binding repertoires","volume":"160","author":"Southwood","year":"1998","journal-title":"J. Immunol."},{"key":"2023012408202532700_b44","doi-asserted-by":"crossref","first-page":"2268","DOI":"10.1172\/JCI25350","article-title":"Natural peptides selected by diabetogenic DQ8 and murine I-Ag7 molecules show common sequence specificity","volume":"115","author":"Suri","year":"2005","journal-title":"J. Clin. Invest."},{"key":"2023012408202532700_b45","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1110\/ps.04631204","article-title":"Modeling the structure of bound peptide ligands to major histocompatibility complex","volume":"13","author":"Tong","year":"2004","journal-title":"Protein Sci."},{"key":"2023012408202532700_b46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1745-7580-2-1","article-title":"Modeling the Bound Conformation of Pemphigus Vulgaris-associated Peptides to MHC Class II DR and DQ Alleles","volume":"2","author":"Tong","year":"2006","journal-title":"Immunome Res."},{"key":"2023012408202532700_b47","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1023\/A:1016357811882","article-title":"Further development and validation of empirical scoring functions for structure-based binding affinity prediction","volume":"16","author":"Wang","year":"2002","journal-title":"J. Comput. Aided Mol. 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