Investigation of molecular interactions between moxetumomab pasudotox and cd22 antigen by structural modeling and protein-protein docking with md simulation

Immunotoxin therapy of cancer is a novel targeted therapy method that has developed based on binding of antibodies to the cancer cell-specific antigens. Immunotoxins are fusion proteins that consistof targeting moiety (monoclonal antibody) and the cell-killing moiety (toxin). Moxetumomab pasudotox or HA22 is a recombinant immunotoxin that targets the CD22 antigen and produced for leukemia treatment. HA22 consists of a dsFv fragment of the RFB4 monoclonal antibody fused to a truncated form of pseudomonas exotoxin A, called PE38. molecular dynamics (MD) simulation is a method for modeling the motions and other characterization of the biomolecule by 3D structures at temporal and spatial scales that are impossible or difficult to access experimentally. In order to identify functional characterization of proteins, the 3D structure of them is determining by experimental methods. While the experimental structure isn’t availability, comparative or homology modeling provide a beneficial 3D structure of the protein based on one or more known 3D protein structure. In this study, we investigated molecular interactions between HA22 and CD22 antigen by protein-protein docking with MD simulation. The 3D structure of HA22 and CD22 antigen is designed by modeller software and based on homology modeling methods. MD Simulation of protein structures was performed in Gromacs software package. Then interactions between HA22 and CD22 antigen were determined by protein-protein docking used HADDOCK web server. We demonstrated the 3D structure of HA22 and CD22 antigen complex and interaction domains between them is determined. This study proved the binding affinity of HA22 in CD22 expression cells and supporting further studies on this novel recombinant drug in the treatment of leukemia

کلیدواژه ها:

Blood Cancer ، Cancer Risks ، Cancer Treatment and Management ، Targeted Cancer Therapy ، Drugs and Cancer