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Influence of catalytic gorge residues

Trainee Achievements

Influence of catalytic gorge residues

Acetylcholinesterase (AChE) is a key enzyme responsible for the hydrolysis of neurotransmitter acetylcholine, terminating synaptic transmission. Organophosphate (OP) compounds such as nerve agents and pesticides irreversibly inhibit AChE and result in neuromuscular paralysis and death by asphyxiation. Current search for reactivating agents of inhibited AChEs are based on known oxime compounds with limited reactivating potentials. Known oximes can not reactivate AChEs once the bound OP undergoes a dealkylation reaction, also known as aging. COB student Sarah Siring carried out all-atom molecular dynamics simulations to study the influence of catalytic gorge residues on organophosphate soman (pinacolyl methyl phosphonofluoridate) coordination within the active site. Furthermore, the mechanism of Soman-AChE aging was studied using Born-Oppenheimer ab initio QM/MM molecular dynamics with umbrella sampling.