Prediction Of Anti-CD47 Antibody Structure Based On Molecular Simulation And Its Humanization

Background and Objective:CD47 is expressed on the surface of a variety of tumor cells and it can interact with the signal-regulating protein SIRPα,thereby reducing the phagocytic capacity of human macrophages,which leads to immune escape of tumor cells.Many studies found that a large amount of CD47 is expressed in many poor prognosis cancer cells.Therefore,the development of anti-CD47 antibodies has important clinical significance for tumor targeted therapy and has broad application prospects.In the early stage,our laboratory obtained two anti-CD47 antibodies with good affinity and specificity through monoclonal antibody screening.In order to further study its properties,we used computers for homology modeling,molecular dynamics simulation and docking of three-dimensional structure antigen molecules to explore the possibility of structural optimization and humanization transformation.Method:We used Discovery Studio for homology modeling of anti-CD47 antibodies to evaluate and analyze their structural rationality,then we used GROMACS for molecular dynamics simulations to deeply analyze the stability of antibody structures and the more flexible amino acid regions in CDR regions Finally,the antibody was docked with the antigen molecule,and the physical and chemical properties of the bound epitope and amino acid residues were analyzed,which was used as a basis for comparison with other anti-CD47 antibodies and humanized transformation,and provided a reference for the next step of antibody structure optimization.Results:We successfully constructed the three-dimensional structure of anti-CD47 antibodies 2C8 and 3A3,and predicted a series of physicochemical properties and binding epitopes of the antibody through molecular dynamics simulation and molecular docking technology,and designed a preliminary humanized transformation plan based on this,Which provides strong data support for the next experiment.Conclusion:Our research successfully analyzed the physicochemical properties and antigen-binding epitopes of anti-CD47 antibodies 2C8 and 3A3 through molecular simulation technology,and humanized transformation based on surface remodeling technology to further improve antibody humanization affinity laid the theoretical foundation.