Effects of Protein Crowders and Charge on the Folding of Superoxide Dismutase1 (SOD1) Variants: A Computational Study

Mutations in the Superoxide Dismutase 1 (SOD1) protein may cause misfolding and aggregation leading to the neurodegenerative disease ALS. Despite numerous studies, a clear understanding of the impact of electrostatics and crowding on the folding and aggregation of SOD1 remains lacking. In this talk, we use a structure-based model and molecular dynamics simulation to study the effects of electrostatics on SOD1 folding in a crowded environment. We show that electrostatics affect the unfolded protein configurations more significantly than the folded ones. Using a new order parameter, we suggest the presence of an intermediate state and show that electrostatics play an important role in the folding pathway of SOD1.