Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	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
Δημιουργός/Συγγραφέας:	Potamitis, C. Matsoukas, M. -T. Tselios, T. [EL] Μαυρομούστακος, Θωμάς[EN] Mavromoustakos, Thomas Grdadolnik, S. Golic
Εκδότης:	Springer
Τόπος έκδοσης:	Dordrecht
Ημερομηνία:	2011-09
Γλώσσα:	Αγγλικά
ISSN:	0920-654X
DOI:	10.1007/s10822-011-9467-4
Περίληψη:	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.
Τίτλος πηγής δημοσίευσης:	Journal of Computer-aided Molecular Design (merged with Perspectives in Drug Discovery and Design)
Τόμος/Κεφάλαιο:	25
Τεύχος:	9
Σελίδες:	837-853
Θεματική Κατηγορία:	[EL] Βιολογία (Γενικά)[EN] Biology (General) [EL] Φυσική[EN] Physics [EL] Ηλεκτρονικοί υπολογιστές. Επιστήμη των υπολογιστών[EN] Electronic computers. Computer science
Λέξεις-Κλειδιά:	Molecular Dynamics (MD) Myelin basic protein (MBP) Conformational analysis Binding motif NMR Multiple sclerosis (MS) Biophysics Computer Science, Interdisciplinary Applications
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© SPRINGER
Ηλεκτρονική διεύθυνση περιοδικού (link) :	http://www.springerlink.com/openurl.asp?genre=journal&issn=0920-654X
ΙΒΦΧΒ: αρχειακή συλλογή:	Ινστιτούτο Οργανικής και Φαρμακευτικής Χημείας (ΙΟΦΧ) (έως 2012)
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο