Next Generation Sequencing And Drug Repositioning Approach For Motor Neuron Disease

Abstract

This investigation employs a multidimensional methodology to explore the intricacies of motor neuron disease (MND), with a specific emphasis on amyotrophic lateral sclerosis (ALS) associated with the mutant SOD1 gene. Through a synthesis of structural examination, computational simulations, and genetic profiling, the study endeavors to elucidate pivotal facets of MND pathology and discern prospective therapeutic interventions. Leveraging sophisticated structural visualization platforms such as Rasmol and PyMOL, the research scrutinizes the intricate three-dimensional framework of the mutant SOD1 protein (PDB ID: 1UXL), elucidating its significance in the progression of the disease. Next-generation sequencing, augmented by sequence homology and phylogenetic analyses, elucidates the genetic foundations of ALS-related MND, furnishing essential insights into disease causation. Molecular docking simulations utilizing CurPocket unveil distinct binding attributes of potential therapeutics, including Riluzole and Gabapentin, within specific loci of the mutant SOD1 protein. Validation via ERRAT, SAVES, and Ramachandran plot analysis confirms the structural robustness of the protein model, reinforcing the reliability of the findings. This integrative approach engenders a comprehensive comprehension of mutant SOD1 in MND, providing valuable perspectives into potential therapeutic avenues for alleviating the debilitating ramifications of this neurodegenerative affliction. By amalgamating structural biology, computational modeling, and genomic scrutiny, this study enriches the evolving corpus of knowledge endeavoring to propel MND research forward and expedite the emergence of tailored therapeutic modalities.