Conformational dynamics of superoxide dismutase (SOD1) in osmolytes: a molecular dynamics simulation study.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease caused by the misfolding of Cu, Zn superoxide dismutase (SOD1). Several earlier studies have shown that monomeric apo SOD1 undergoes significant local unfolding dynamics and is the predecessor for aggregation. Here, we have employed atomistic molecular dynamics (MD) simulations to study the structure and dynamics of monomeric apo and holo SOD1 in water, aqueous urea and aqueous urea-TMAO (trimethylamine oxide) solutions. Loop IV (zinc-binding loop) and loop VII (electrostatic loop) of holo SOD1 are considered as functionally important loops as they are responsible for the structural stability of holo SOD1. We found larger local unfolding of loop IV and VII of apo SOD1 as compared to holo SOD1 in water. Urea indu

SUBMITTER: Jahan I 

PROVIDER: S-EPMC9055598 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature