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Genetic tendency has an important role in its pathogenesis, and HLA\u2010B51, a class I MHC antigen, has been recognized as the strongest susceptibility factor for Beh\u00e7et's disease. Despite the confirmation of the association of HLA\u2010B51 with Beh\u00e7et's disease in different populations, its pathogenic mechanisms remain elusive. HLA\u2010B51 differs in only two amino acids from HLA\u2010B52, other split antigen of HLA\u2010B5, which is not associated with Beh\u00e7et's disease. These two amino acids are located in the B pocket of the antigen\u2010binding groove, which occupies the second amino acids of the bound peptides. To understand the nature of the HLA\u2013peptide interactions, differences in structure and dynamics of two HLA alleles were investigated by molecular dynamics simulations using YAYDGKDYI, LPRSTVINI, and IPYQDLPHL peptides. For HLA\u2010B51, all bound peptides fluctuated to larger extent than HLA\u2010B52. Free energy profiles of unbinding process for YAYDGKDYI by steered molecular dynamics simulations showed that unbinding from HLA\u2010B52 results in greater free energy differences than HLA\u2010B51. These results suggest the possibility of an instability of HLA\u2010B51 associated with the repertoire of peptides, and this finding may provide significant insight to its pathogenic role in Beh\u00e7et's disease.<\/jats:p>","DOI":"10.1111\/cbdd.13658","type":"journal-article","created":{"date-parts":[[2020,7,21]],"date-time":"2020-07-21T11:23:19Z","timestamp":1595330599000},"page":"644-658","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Molecular dynamics simulations provide molecular insights into the role of HLA\u2010B51 in Beh\u00e7et's disease pathogenesis"],"prefix":"10.1111","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0983-4397","authenticated-orcid":false,"given":"Mert","family":"Gur","sequence":"first","affiliation":[{"name":"Department of Mechanical Engineering Faculty of Mechanical Engineering Istanbul Technical University (ITU) Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5476-8160","authenticated-orcid":false,"given":"Mert","family":"Golcuk","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering Faculty of Mechanical Engineering Istanbul Technical University (ITU) Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8219-3720","authenticated-orcid":false,"given":"Ahmet","family":"Gul","sequence":"additional","affiliation":[{"name":"Division of Rheumatology Department of Internal Medicine Istanbul Faculty of Medicine Istanbul University Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2496-6059","authenticated-orcid":false,"given":"Burak","family":"Erman","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering, College of Engineering Koc University Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,21]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"Molecular biology of the cell","author":"Alberts B.","year":"2015"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/ct300400x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0105-2896.2009.00865.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24642"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-38788-0"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0066178"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/7.2.223"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00408"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-47001-1"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2006.08.294"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)61128-3"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.789180"},{"issue":"5","key":"e_1_2_8_14_1","first-page":"S6","article-title":"Behcet's disease: an update on the pathogenesis","volume":"19","author":"Gul A.","year":"2001","journal-title":"Clinical and Experimental Rheumatology"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-015-0502-8"},{"key":"e_1_2_8_16_1","first-page":"265","volume-title":"Genetics of Beh\u00e7et's disease Beh\u00e7et's syndrome","author":"G\u00fcl A.","year":"2010"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2010.85"},{"key":"e_1_2_8_18_1","unstructured":"Hildebrand W. 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