Publication:
Molecular dynamics simulations provide molecular insights into the role of HLA-B51 in Behcet's disease pathogenesis

dc.contributor.coauthorGür, Mert
dc.contributor.coauthorGölcük, Mert
dc.contributor.coauthorGül, Ahmet
dc.contributor.departmentDepartment of Chemical and Biological Engineering
dc.contributor.kuauthorErman, Burak
dc.contributor.kuprofileFaculty Member
dc.contributor.yokid179997
dc.date.accessioned2024-11-10T00:00:28Z
dc.date.issued2020
dc.description.abstractBehcet's disease is an inflammatory disorder of unknown etiology. Genetic tendency has an important role in its pathogenesis, and HLA-B51, a class I MHC antigen, has been recognized as the strongest susceptibility factor for Behcet's disease. Despite the confirmation of the association of HLA-B51 with Behcet's disease in different populations, its pathogenic mechanisms remain elusive. HLA-B51 differs in only two amino acids from HLA-B52, other split antigen of HLA-B5, which is not associated with Behcet's disease. These two amino acids are located in the B pocket of the antigen-binding groove, which occupies the second amino acids of the bound peptides. To understand the nature of the HLA-peptide interactions, differences in structure and dynamics of two HLA alleles were investigated by molecular dynamics simulations using YAYDGKDYI, LPRSTVINI, and IPYQDLPHL peptides. For HLA-B51, all bound peptides fluctuated to larger extent than HLA-B52. Free energy profiles of unbinding process for YAYDGKDYI by steered molecular dynamics simulations showed that unbinding from HLA-B52 results in greater free energy differences than HLA-B51. These results suggest the possibility of an instability of HLA-B51 associated with the repertoire of peptides, and this finding may provide significant insight to its pathogenic role in Behcet's disease.
dc.description.indexedbyWoS
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.issue1
dc.description.openaccessNO
dc.description.publisherscopeInternational
dc.description.volume96
dc.identifier.doi10.1111/cbdd.13658
dc.identifier.eissn1747-0285
dc.identifier.issn1747-0277
dc.identifier.quartileQ3
dc.identifier.scopus2-s2.0-85088278513
dc.identifier.urihttp://dx.doi.org/10.1111/cbdd.13658
dc.identifier.urihttps://hdl.handle.net/20.500.14288/15803
dc.identifier.wos550342600001
dc.languageEnglish
dc.sourceChemical Biology and Drug Design
dc.subjectBiochemistry
dc.subjectMolecular biology
dc.titleMolecular dynamics simulations provide molecular insights into the role of HLA-B51 in Behcet's disease pathogenesis
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.authorid0000-0002-2496-6059
local.contributor.kuauthorErman, Burak
local.publication.orgunit1College of Engineering
local.publication.orgunit2Department of Chemical and Biological Engineering
relation.isOrgUnitOfPublicationc747a256-6e0c-4969-b1bf-3b9f2f674289
relation.isOrgUnitOfPublication.latestForDiscoveryc747a256-6e0c-4969-b1bf-3b9f2f674289

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