In silico study of the association of the HLA-A*31:01 allele (human leucocyte antigen allele 31:01) with neuroantigenic epitopes of PLP (proteolipid protein), MBP (myelin basic protein) and MOG proteins (myelin oligodendrocyte glycoprotein) for studying the multiple sclerosis disease pathogenesis

A Journey to the Conformational Analysis of T-Cell Epitope Peptides Involved in Multiple Sclerosis

“…It was found that the A_31:01 allele may be associated with the MS disease and the peptide Leu-Ile-Ile-Cys-Tyr-Asn-Trp-Leu-His-Arg may serve as a potential epitope to this allele. This finding must be confirmed by experimental evidence [79].…”

“…This cyclic analogue illustrated comparable bioactivity with the linear one, confirming that the possible bioactive conformation of MBP [74][75][76][77][78][79][80][81][82][83][84][85] resembles that of the cyclic variant or the cyclic variant resembles more, from the available ensemble, the structure of the linear peptide that is of biological significance. The structures of the linear and cyclic analogues are shown in Figure 8.…”

“…Tzakos et al [48] applied NMR and molecular dynamic simulations to study the conformational properties of agonist MBP, Gln 74 Arg 78 adopted a well-defined conformation, which did not depend on the solvent. Such electrostatic interactions were not observed in the antagonist Ala 81 MBP (74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85), and a high flexibility of the side chain of Arg 78 was observed. The positively charged residue Arg 78 is suggested to stabilize the local microdomains (epitopes) of the integral protein.…”

“…In another study the conformational analysis of the immunodominant epitope of acetylated myelin basic protein residues 1-11 (Ac-MBP1-11) and its ALPs, mutated at position 4 to an alanine (Ac-MBP1-11(4A)) or a tyrosine residue (Ac-MBP1-11(4Y)), was achieved. The amino acids Tzakos et al [48] applied NMR and molecular dynamic simulations to study the conformational properties of agonist MBP, Gln 74 -Lys 75 -Ser 76 -Gln 77 -Arg 78 -Ser 79 -Gln 80 -Asp 81 -Glu 82 -Asn 83 -Pro 84 -Val 85 (MBP (74-85) ), and its antagonist analogue Ala 81 MBP (74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85) . The agonist MBP (74-85) adopted a compact conformation attributed to electrostatic interactions of Arg 78 with the side chains of Asp 81 and Glu 82 .…”

“…The positively charged residue Arg 78 is suggested to stabilize the local microdomains (epitopes) of the integral protein. Flexible docking calculations point out that Gln 74 , Ser 76 and Ser 79 are MHC II anchor residues. Lys 75 , Arg 78 and Asp 81 are the mainly solvent-exposed residues and this may signify their participation in the formation of the trimolecular T-cell receptor-MBP (74-85) -MHC II complex.…”