Molecular dynamics simulation reveals the selective binding of human leukocyte antigen alleles associated with behçet's disease

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© 2015 Kongkaew et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Behçet's disease (BD), a multi-organ inflammatory disorder, is associated with the presence of the human leukocyte antigen (HLA) HLA-B∗51 allele in many ethnic groups. The possible antigen involvement of the major histocompatibility complex class I chain related gene A transmembrane (MICA-TM) nonapeptide (AAAAAIFVI) has been reported in BD symptomatic patients. This peptide has also been detected in HLA-A∗26:01 positive patients. To investigate the link of BD with these two specific HLA alleles, molecular dynamics (MD) simulations were applied on the MICA-TM nonapeptide binding to the two BD-associated HLA alleles in comparison with the two non-BD-associated HLA alleles (B∗35:01 and A∗11:01). The MD simulations were applied on the four HLA/MICA-TM peptide complexes in aqueous solution. As a result, stabilization for the incoming MICA-TM was found to be predominantly contributed from van der Waals interactions. The P2/P3 residue close to the N-terminal and the P9 residue at the C-terminal of the MICA-TM nonapeptide served as the anchor for the peptide accommodated at the binding groove of the BD associated HLAs. The MM/PBSA free energy calculation predicted a stronger binding of the HLA/peptide complexes for the BD-associated HLA alleles than for the non-BD-associated ones, with a ranked binding strength of B∗51:01 > B∗35:01 and A∗26:01 > A∗11:01. Thus, the HLAs associated with BD pathogenesis expose the binding efficiency with the MICA-TM nonapeptide tighter than the non-associated HLA alleles. In addition, the residues 70, 73, 99, 146, 147 and 159 of the two BD-associated HLAs provided the conserved interaction for the MICA-TM peptide binding.




Kongkaew, S., Yotmanee, P., Rungrotmongkol, T., Kaiyawet, N., Meeprasert, A., Kaburaki, T., … Hannongbua, S. (2015). Molecular dynamics simulation reveals the selective binding of human leukocyte antigen alleles associated with behçet’s disease. PLoS ONE, 10(9).

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