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Conformational analysis of the MBP(83-99) (Phe(91)) and MBP(83-99) (Tyr(91)) peptide analogues and study of their interactions with the HLA-DR2 and human TCR receptors by using Molecular Dynamics

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Conformational analysis of the MBP(83-99) (Phe(91)) and MBP(83-99) (Tyr(91)) peptide analogues and study of their interactions with the HLA-DR2 and human TCR receptors by using Molecular Dynamics
Potamitis, C.
Μαυρομούστακος, Θωμάς
Matsoukas, M. -T.
Grdadolnik, S. Golic
Tselios, T.
Άρθρο σε επιστημονικό περιοδικό
2011-09
Dordrecht
The two new synthetic analogues of the MBP83-99 epitope substituted at Lys(91) (primary TCR contact) with Phe [MBP83-99 (Phe(91))] or Tyr [MBP83-99 (Tyr 91)], have been structurally elucidated using 1D and 2D high resolution NMR studies. The conformational analysis of the two altered peptide ligands (APLs) has been performed and showed that they adopt a linear and extended conformation which is in agreement with the structural requirements of the peptides that interact with the HLA-DR2 and TCR receptors. In addition, Molecular Dynamics (MD) simulations of the two analogues in complex with HLA-DR2 (DRA, DRB1*1501) and TCR were performed. Similarities and differences of the binding motif of the two analogues were observed which provide a possible explanation of their biological activity. Their differences in the binding mode in comparison with the MBP83-99 epitope may also explain their antagonistic versus agonistic activity. The obtained results clearly indicate that substitutions in crucial amino acids (TCR contacts) in combination with the specific conformational characteristics of the MBP83-99 immunodominant epitope lead to an alteration of their biological activity. These results make the rational drug design intriguing since the biological activity is very sensitive to the substitution and conformation of the mutated MBP epitopes.
Ηλεκτρονικοί υπολογιστές. Επιστήμη των υπολογιστών (EL)
Βιολογία (Γενικά) (EL)
Φυσική (EL)
Biology (General) (EN)
Electronic computers. Computer science (EN)
Physics (EN)
NMR
Computer Science, Interdisciplinary Applications
Myelin basic protein (MBP)
Multiple sclerosis (MS)
Conformational analysis
Molecular Dynamics (MD)
Binding motif
Biophysics
English
Springer
Journal of Computer-aided Molecular Design (merged with Perspectives in Drug Discovery and Design)
https://rightsstatements.org/page/InC/1.0/?language=en
© SPRINGER
© SPRINGER (EN)
National Hellenic Research Foundation (NHRF)
Helios - Repository of the National Hellenic Research Foundation (NHRF)



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