HOMOLOGY MODELING, DOCKING STUDIES, AND MOLECULAR DYNAMICS SIMULATION OF ISOCITRATE DEHYDROGENASE TYPE 1 (R132H) EPITOPES AS GLIOMA VACCINE CANDIDATES

• Main Author: Yeni
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/78953
• Institution: Institut Teknologi Bandung

Glioma is a type of primary malignant brain tumor. The presence of gliomas can be characterized by a mutation R132H of isocitrate dehydrogenase type 1 (IDHI). IDHI (R132H) contains specific immunogenic epitopes to the tumor. It is appropriate to be used as a gliomas vaccine. Therefore, it was necessary to do homology modeling, docking study and molecular dynamics simulation for IDHI (R132H) epitopes. TMHMM, MEMSAT-SVM and MEMSAT3 were used to predict transmembrane topology of IDHI (R132H). Analysis of IDHI (R132H) epitopes was performed using NetMHCII and IEPB@. The antigenicity of epitopes were predicted using VaxiJen to obtained 91 epitopes. Homology modeling using Modeller, I-TASSER and (PS)2 was established for the epitopes that have probability as tumor antigen. The results of homology modeling of IDHI (R132H) epitopes were validated by MolProbity, ProSA-web dan QMEAN. A 3D stucture model of the epitopes was selected from three models from the homology modeling based on the validation results. Refinement was established on the epitopes using GalaxyRefine and GROMACS for energy minimization. The epitopes were docked to MHC Il HLA DRBI 0101 to determine their preventive function and to EphA3 to determine their curative function. It was performed by using Dock. Epitope 42 have the greatest binding affinity to MHC Il HLA DRBI 0101, while epitope 54 have the greatest binding affinity to EphA3 receptor. Molecular dynamics simulation using GROMACS showed that the complex of epitope 42-MHC Il HLA DRBI 0101 was relatively stable at 1.72 to 12.34 ns, while the complex of epitope 54-EphA3 receptor was stable from the beginning of the simulation to 15.29 ns.