In Silico Research in Glioma Vaccine Discovery from Isocitrate Dehydrogenase Type 1 (R132H) Epitopes

Abstract

Glioma is a primary malignant brain tumor, which is often detected using the mutation of isocitrate dehydrogenase type 1 (IDH1) at the R132H position. Several studies have also reported the use of mutated IDH1 (R132H) specific immunogenic epitopes as vaccines against this tumor. Therefore, this study aimed to determine the high-affinity epitopes of IDH1 (R132H) as a plausible candidate of preventive and curative glioma vaccines and to predict the stability of epitope-receptor complex through molecular dynamics simulation. The binding affinity of epitopes for preventing and treating glioma were predicted by docking epitope to major histocompatibility complexes class II (MHC II) and ephrin type-A receptor 3 (EphA3), respectively, using Dock version 6.7. This study used the rigid body docking method, where the samples were treated in their compact state. The highest binding affinity for MHC II was exhibited by epitope 42, as indicated by a grid score of -62.73 kcal/mol. Meanwhile, epitope 54, with a grid score of -55.56 kcal/mol, had the highest binding affinity for the EphA3 receptor. The results showed that the protein conformation in the 42-MHC II epitope complex changed significantly in molecular dynamics simulations using GROMACS version 5.0.6 at 300 K for 25 ns with RMSD > 3 Å, while epitope 54-EphA3 complex was stable from the beginning up to 15.29 ns. Based on these findings, the best candidates for prophylactic and curative glioma vaccination were epitope 42 and 54, respectively.