Mutations in the gene encoding Cu/Zn Superoxide Dismutase 1 (SOD1) protein are contemplated to be a protruding reason for Amyotrophic lateral sclerosis (ALS), which leads towards protein aggregation, misfolding and destabilization. Thus, we investigated the systematic action of entire mutations reported on electrostatic loop of SOD1 protein through thermodynamical and discrete molecular dynamics (DMD) studies. Accordingly, we analyzed the outcomes distinctly for screening the mutant structures having both, deleterious and destabilizing effect. Progressively, the impacts of those mutations on SOD1 were studied using DMD program. Surprisingly, our results predicted that the mutants viz., L126S, N139H and G141A to be the most destabilizing, misfolded and disease-causing compared to other mutants. Besides, the outcomes from secondary structural propensities and free energy landscapes, together assertively suggested that L126S, N139H and G141A tend to increase the formation of aggregates in SOD1 relative to other mutants. Hence, this study could provide an insight into the sprouting neurodegenerative disorder distressing the humans. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.