Research On The Theoretical Calculation Of The Interaction Between The Immune Regulatory Protein Mutant Of Ganoderma Lucidum And EGFR

In recent years,with the advancement of technology and the development of medical treatment,the survival rate of global malignant tumors has been increasing year by year,but the survival rate of malignant tumors in China over the past 5 years is only 40.5%.The continuous proliferation of malignant tumors is the main feature of cancer,tumor cells overcome growth limitations and continuously proliferate within the tumor microenvironment can be attributed to dysregulation in the signaling cascade of growth factors and their receptors.Research on the active sites of malignant tumors and the development of new inhibitory drugs are expected to improve survival rates.In addition,the interaction between existing malignant tumor suppressing drugs and epidermal growth factor receptor(EGFR)sites is expected to achieve precise control of tumors.In this thesis,the biological allosteric status of the EGFR transmembrane domain was studied by molecular docking and molecular dynamics simulation methods,and the experimental study and molecular dynamics calculation of the binding posture of ganoderma lucidum immunomodulatory protein mutants and EGFR were performed.The details are as follows:(1)The molecular dynamics method was used to study the allosteric study of EGFR transmembrane domain in biofilm and the screening study of EGFR transmembrane domain small molecule inhibitors.According to the amino acid sequence of EGFR in the NCBI database and related literature data to determine the sequence of EGFR transmembrane domain,using molecular dynamics methods tostudy the EGFR transmembrane domain dimer,combined with the angle of motion locus we can speculate that EGFR transmembrane the dimer of the domain dimer spirals inwards,and the secondary structure of the EGFR transmembrane domain dimer is basically stable.Using small molecule screening methods to screen EGFR transmembrane domain dimer inhibitors,200 compounds were screened ZINC structure.(2)Through chemical crosslinking combined with mass spectrometry experiment and molecular dynamics calculation,the binding posture of Ganoderma lucidum immunomodulating protein mutant and EGFR was studied.By identifying the lysine and serine residues of two proteins that are adjacent to each other and covalently bound,the distance information between EGFR and ganoderma immunoregulatory protein is obtained.Isothermal titration calorimetry(ITC)was used to detect the extracellular domain(ECD)of purified EGFR and ganoderma immunoregulatory protein.An EGFR molecule was combined with the dimer of ganoderma immunoregulatory protein.The ganoderma lucidum immunomodulatory protein mutant and EGFR were docked by molecular docking.By analyzing the binding posture of ganoderma lucidum immunomodulatory protein mutant and EGFR,the amino acid of ganoderma lucidum immunomodulatory protein mutant interacted with the EGFR group.Stability experiments were conducted on the simulation of the interaction between ganoderma lucidum immunomodulatory protein mutants and EGFR.The structure and relative position of EGFR and ganoderma lucidum immunomodulatory protein mutants remained stable,and the fluctuation of the four relatively stable key amino acid residues was small.In summary,this thesis uses molecular mechanics and molecular docking techniques to determine the stability of EGFR transmembrane domains on biofilms.On this basis,200 compound inhibitors were obtained using virtual screening;A keybinding site for the interaction between EGFR and Ganoderma immunomodulatory protein mutants was found.This paper can provide new ideas for the development of anti-tumor drugs targeting EGFR.