The Study Of The Interaction Between Antigen Peptide And MHC Class Ⅰ Based On QM/MM Molecular Dynamics Simulation

In the process of antigen presenting of major histocompatibility complex (MHC) class I molecule, Antigen protein, which is in the cytoplasm of antigen-presenting cells(APC), is cleaved into short peptide fragments by proteasome, and the short peptide fragments will be transferred from the cytoplasm to the endoplasmic reticulum lumen by transporter associated with antigen processing(TAP). The peptide will combine with the newly generated MHC class I molecule, and the forming pMHC complex will be presented to the surface of APC cells, and it will be recognized by T cell receptor(TCR). After these process, the CTL cells will be activated, and it will begin to proliferate and differentiate, and then, the process of specific cytotoxicity about the tumor cells will start. In this paper, we use QM/MM multi-scale molecular dynamics simulation to biological macromolecules, and take the crystal structure HLA-A*0201molecules complex as the template. We would replace the anchor amino acid residue of the peptide, and we use the electric multipole moment component to present the electrostatic potential formed by the atomic polarization charge of pocket amino acid residues. We analysis the electrostatic potential changes and the functions of each pocket amino acid by box plots, we would consider that GLU63and LYS66of Pocket B are primary anchoring amino acids and fine recognition amino acid, ASP77and TYR84of Pocket F are the fine recognition amino acid, ASP77and LYS146are the primary anchoring amino acids. It shows that QM/MM method is very effective in extracting the specific information of antigen peptide binding to MHC class I molecules. And it possesses some guiding significance to understand the mechanism of immune recognition and the development of tumor vaccine.