Study On The Application Of MMPBS_IE Method In HLA System

With the rapid development of computer technology,computational simulation has become an important means to study physics,chemistry,biology and many other disciplines.In bioscience,the experimental workload for biological macromolecules,disease mechanism unveiling,and drug research and development is usually too large,and computational simulation can make up for this shortcoming.In this paper,Amber’s enthalpy calculation(MM/PBSA)was combined with our group’s entropy calculation(IE),alanine scanning(AS)was used to determine the hot residues at the protein-protein interaction interfaceHLA(Human Leukocyte Antigen)is an important part of human cellular immunity and is associated with various diseases,such as ankylosing spondylitis,reactive arthritis,and celiac disease.HLA is divided into HLA type I proteins and HLA type II proteins,and participates in human immune response through two immune pathways respectively.The first two topics in this paper respectively involve these two HLA proteinsThe second chapter is about the mechanism of HLA-II protein on small intestinal celiac disease.Based on four protein crystal structures from three different patients,the important interactions between HLA II and Peptide,and the interactions between TCR and HLA II,TCR and Peptide in the recognition of HLA II Peptides were analyzed in detail through molecular dynamics simulation and free energy calculation By analyzing the process of TCR recognition of HLA II Peptide,it can be concluded that although the TCR sequence is not identical in everyone,some hot spots and important interactions are highly conserved,and these highly conserved residues may be the key to triggering CD disease.On this basis,the mechanism of activation of TCR by HLA-DQ8 Peptide complex is summarized.At the same time,glutamine residue(Q)in Peptide plays an irreplaceable role in the recognition of TCR.It is hoped that this work can help to understand the pathogenic mechanism of celiac disease and provide clues for the development of corresponding drugsChapter 3 is devoted to the study of the binding process of HLA-I proteins to Peptide.HLA-I proteins are found in all nucleated cells and are responsible for delivering endogenous proteins to the cell surface.This paper attempts to analyze the binding characteristics of HLA-A02 protein that can bind multiple peptides by performing molecular dynamics simulation and free energy calculation on two protein systems containing the same HLA but different peptides.The study found that when the same HLA-A02 protein presents different peptides,although there are some different hot spot residues on the binding surface,but all of them are given priority to hydrophobic residues with aromatic ring,a small amount of charged residues is complementary.The combined peptide is a single arch and interacts with HLA-I mainly through the residues on its two wings.Because HLA-A02 protein is related to type 1 diabetes,it is hoped that this work can help us to understand the binding mechanism of HLA-A02-related type 1 diabetes and provide help for the study of its pathogenic causeThe fourth chapter is about the kinetic study of the Folic acid transporter FolT Folic acid,due to its unique molecular structure,is involved in the synthesis of pyrimidines and purines in the body,and thus in some of the body’s important physiological reactions,such as mitosis.Inadequate intake can lead to diseases such as neural tube abnormalities,anemia,cleft lip and palate,and depression.In this paper,through conventional kinetics,SMD and RAMD-MD simulation methods,the molecular dynamics simulations of the folic acid transporter were carried out.And it was concluded that Loop 1 plays an important gating function in the folic acid transport process and controls the folic acid entry and release process.It is hoped that this article can help to understand folic acid deficiency caused by insufficient folic acid absorption.