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 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). And then, the CTL cells will be activated, and it will begin to proliferate and differentiate, and it will kill the tumor cells. The mechanisms how does the CTL cell recognize the peptide-MHC complex and how does the MHC molecule interact with the peptide are not clear. In traditional method, electronic structure changes is not considered during the peptide binding to the MHC molecules. The electronic structure changes need to use the method of Quantum Mechanics to deal with. In this paper, we use QM/MM multi-scale molecular dynamics simulation of biological macromolecules, and take the crystal structure of TAX-HLA- A*0201 molecules complex as template. We would replace the anchor amino acid of the peptide, and use the electric multipole moment component to present the electrostatic potential formed by the atomic polarization charge of pocket amino acid residues. We analyze the electrostatic potential changes and the functions of each pocket amino acid by box plots, we would consider that Glu63 and Lys66 of Pocket B are primary anchoring amino acids and fine recognition amino acid, Asp77 and Tyr84 of Pocket F are the fine recognition amino acid, Asp77 and Lys146 are 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.

Key words: QM/MM molecular dynamic simulation, electric multipole moment, T cell epitope, exogenous antigen, MHC class I molecules