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

Jingjing Guo, Xiaoting Wang, Huijun Sun, Huanxiang Liu, Yulin Shen, Xiaojun Yao

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1025-1032
Number of pages8
JournalChemical Biology and Drug Design
Volume79
Issue number6
DOIs
Publication statusPublished - Jun 2012
Externally publishedYes

Keywords

  • 2009 influenza A virus
  • 3501
  • HLA-B
  • Molecular dynamics simulation
  • NP
  • PMHC-I

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