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The Evolution of HLA‐B*3501 Binding Affinity to Variable Immunodominant NP 418‐426 Peptides from 1918 to 2009 Pandemic Influenza A Virus: A Molecular Dynamics Simulation and Free Energy Calculation Study
Author(s) -
Guo Jingjing,
Wang Xiaoting,
Sun Huijun,
Liu Huanxiang,
Shen Yulin,
Yao Xiaojun
Publication year - 2012
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2012.01357.x
Subject(s) - cytotoxic t cell , virus , human leukocyte antigen , virology , epitope , biology , major histocompatibility complex , influenza a virus , molecular dynamics , antigen , mutant , chemistry , in vitro , gene , genetics , computational chemistry
Virus‐specific cytotoxic T lymphocytes contribute to the control of virus infections including those caused by influenza viruses. However, during the evolution of influenza A viruses, variations in cytotoxic T lymphocytes epitopes have been observed and it will affect the recognition by virus‐specific cytotoxic T lymphocytes and the human virus‐specific cytotoxic T lymphocytes response in vitro . Here, to gain further insights into the molecular mechanism of the virus‐specific cytotoxic T lymphocytes immunity, the class I major histocompatibility complex‐encoded HLA‐B*3501 protein with six different NP 418‐426 antigenic peptides emerging from 1918 to 2009 pandemic influenza A virus were studied by molecular dynamics simulation. Dynamical and structural properties (such as atomic fluctuations, solvent‐accessible surface areas, binding free energy), based on the solvated protein‐peptide complexes, were compared. Free energy calculations emphasized the important role of the secondary anchors (positions 2 and 9) in influencing the binding of MHC‐I with antigenic non‐apeptides. Furthermore, major interactions with peptides were gained from HLA‐B*3501 residues: Tyr7, Ile66, Lys146, Trp147, and Tyr159. Detailed analysis could help to understand how different NP 418‐426 mutants effectively bind with the HLA‐B*3501.