Molecular dynamics simulation of wild and mutant proteasome subunit beta type 8 (PSMB8) protein: Implications for restoration of inflammation in experimental autoimmune encephalomyelitis pathogenesis.

Multiple Sclerosis (MS) is an autoimmune and chronic disease in the brain and spinal cord. MS has inflammatory progression characterized by its hallmark inflammatory plaques. The histological and clinical characteristics of MS are shared by Experimental Autoimmune Encephalomyelitis (EAE). Genetic and environmental factors contribute to the development of MS. In EAE-MS disease, the level of proteasome subunit beta type-8 (PSMB8), encoded by the PSMB8 gene, is increased and regulates the inflammatory response in this disease. In humans, the Nakajo-Nishimura Syndrome is caused by a mutation in the gene PSMB8, a part of the immunoproteasome subunit. Therefore, special attention to wild and mutant (G210V) PSMB8 protein is imperative. In this study, we performed a 100 ns molecular dynamics (MD) simulation for wild-type PSMB8 and the mutant G210V. Then, we analyzed the fundamental and essential simulation results using another Google Colab system. The energy analysis ensures the structural deviation due to point mutation. The trajectory of the fundamental simulation (RMSD, RMSF, and Rg) describes that the G210V mutated protein is more flexible and less stable than the wild type. We observed the conformational changes due to mutation by analyzing the RMSD average linkage hierarchical clustering, total SASA, and SASA autocorrelation. The differences in the protein's overall motion and the atoms' precise location are identified by the principal component analysis, showing that the overall motion and location of the atoms are different. Our study provides valuable insights into the dynamics and structure of this protein, which can aid in further understanding its biological functions and potential implications for disease.