Molecular Dynamics Simulation Study Of The Interaction Between TCR And PMHC Class I Based On QM/MM Method

The cell specific immunity is one of the basic functions of human immunity system. T cell epitope is the key factor to elicit this immune response. However it cannot be recognized by T cell receptor directly, because it hides inside the antigen. A series of processing and presentation should be done to the T cell epitope before it is bound to the MHC class I molecule. The complex composed of the epitope and MHC molecule is transported to the face of Antigen presenting cell for the recognition of T cell receptor with the immune response activated. In this paper, we take the TCR-TAX-pMHC*0201 protein crystal structure as the template, and use QM/MM method to do the molecular dynamics simulation. We would replace the anchor amino acid of the peptide with the rest 19 amino acids, and empress the electric multipole moment with the pocket amino acid polarization charge, with which we can compute the electrostatic potential changes. We analyze the functions of each pocket amino acid by box plots. Through analysis, we got that Lys66, Glu63 in Pocket 2 and Lys146, Asp77 in Pocket 9 are primary anchoring; Lys66, Glu63 in Pocket 2 and Asp77, Tyr84 in Pocket 9 are fine recognition amino acids, which can illustrate that these two pockets basically determine the specific combination between MHC class I and peptide. The electrostatic potential changes of pocket amino acids in TCR are generally larger than those in MHC, suggesting that TCR plays a main role in immune specific recognition and anchoring. Arg590 in Pocket 5 is not only a primary anchoring amino acid but also a fine recognition amino acid, which can indicate that this pocket is very important in TCR. This paper confirms that it is a feasible method to study the specific protein recognition with the QM/MM molecular dynamics simulation.