Simulation Modeling of A3243g Mutations on tRNALeu (UUR) against Type 2 Diabetes Mellitus using In Silico Method

Abstract

Mitochondrial disease is a disease that affects the genetic condition of mitochondrial DNA. One of the causes of this disease is the mutation of nucleotide bases A to G at the 3243 nucleotide position of the mtDNA tRNALeu (UUR) gene. The characteristic of the mutation A3243G mtDNA is a heteroplasmic mutation with a relatively low amount of mutant DNA. The mutants that occur can undergo a dimerization process which can reduce aminoacylation. The purpose of this study was to prove in silico the effect of mitochondrial DNA mutation A3243G tRNA leucine on type 2 diabetes mellitus. The stages of the research carried out included structural modeling of tRNALeu and Protein tRNA Synthetase using the homology method, then a native and mutant leucine tRNA model was made. The results of the modeling were assessed and validated. The next step is the dimerization process between mutant tRNAs to see the binding of structures to the tRNA. The next process is docking between the tRNA and protein models. The final step is to simulate molecular dynamics in the native tRNA model, mutants and dimer structures to see the differences in aminoacylation reactions in the three models in mitochondria. This study is expected to provide information about the effect of the A3243G mutation on the causes of type 2 diabetes in mitochondria.