Protein aggregation is a hallmark of various neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS) in humans. Mutations in Cu/Zn superoxide dismutase (SOD1) protein were found to be a prominent cause behind the majority of the familial ALS cases with abnormal protein aggregates. Herein, we report the biophysical characterization of the beneficial mutation C111S that stabilizes the SOD1 harboring A4V mutation, one of the most lethal diseases causing mutant that leads to protein destabilization and aggregation. In this study, we utilized discrete molecular dynamics (DMD) simulations, which stipulated an outlook over the systematic action of C111S mutation in the A4V mutant that stabilizes the protein and impedes the formation of protein aggregation. Herewith, the findings from our study manifested that the mutation of C111S in SOD1 could aid in regaining the protein structural conformations that protect against the formation of toxic aggregates, thereby hindering the disease pathogenicity subtly. Hence, our study provides a feasible pharmaceutical strategy in developing the treatment for incurable ALS affecting the mankind. © 2017, Springer Science+Business Media, LLC.