Computational analysis on the binding of epitope peptide to human leukocyte antigen class I molecule A*2402 subtype.

摘要: Immunological response induced by small amino peptide has attracted much recent attention in the field of immunotherapy. Wilms' tumor (WT1) protein is one potent antigens inducing immunological mouse and human, because WT1 over expressed many types leukemia various kinds solid tumors. A 9-mer encoded (CMTWNQMNL; acid 235-243) known to serve as antigenic for human leukocyte antigen (HLA)-A*2402 molecule. It was reported that replacement second residue, which deeply responsible binding HLA, strong compared natural peptide. In this study, 19 single substitutions were introduced at position 2 We performed molecular dynamics simulation on complex each epitope peptides HLA-β2 micro globulin (β2m) molecule, subsequently estimated affinity using mechanics/generalized-Born surface area method combined with normal mode analysis. Our computation indicated containing M2Y or M2W mutation showed high HLA-β2m molecule well have also examined role residue HLA-β2m. The calculation van der Waals interaction between side chain hydrophobic residues inside B-pocket HLA are important. These findings will be helpful search other enhance specific HLA-A*2402