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چکیده
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Protein aggregation is a biological process that occurs when proteins misfold. Misfolding of human superoxide dismutase 1 (hSOD1) leads to the neurodegenerative disease amyotrophic lateral sclerosis (ALS). The E49K mutation in the hSOD1 gene increases the amyloidogenic behavior of the protein. This research aims to investigate the impact of Ethyl Ammonium Bromide (EAB) ionic liquid on the E49K mutant using Molecular docking and molecular dynamics simulation. The initial structure of WT-SOD1for the MD simulations was obtained from the PDB ID: 2C9V. The E49K mutation was introduced into the file using Pymol software. Subsequently, molecular dynamics simulation in GROMACS software was utilized to assess the mutation's effect on protein structure stability, using RMSD and radius of gyration. The average RMSD values for WT-SOD1 and the mutant were 0.31 and 0.18 nm, respectively, increasing to 0.24 after binding EAB to the mutant protein. During the simulation, the average Rg values for WTSOD1 and E49K were 1.98 and 1.99 nm, respectively, reaching 2.01 due to the interaction of EAB with E49K. While there was no significant difference in the average Rg values of the E49K mutant and its complex with EAB, the RMSD values indicated that the EAB-E49K complex enhances the structural similarity between WT-SOD1 and E49K. In general, molecular simulation studies and the utilization of ionic liquids can provide valuable insights into both preventing and potentially restoring amyloid formation in ALS disease.
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