Enzyme Dynamics Determine the Potency and Selectivity of Inhibitors Targeting Disease-Transmitting Mosquitoes.

ABSTRACT: Vector control of mosquitoes with insecticides is an important tool for preventing the spread of mosquito-borne diseases including malaria, dengue, chikungunya, and Zika. Development of active ingredients for insecticides are urgently needed because existing agents exhibit off-target toxicity and are subject to increasing resistance. We therefore seek to develop noncovalent inhibitors of the validated insecticidal target acetylcholinesterase 1 (AChE1) from mosquitoes. Here we use molecular dynamics simulations to identify structural properties essential for the potency of reversible inhibitors targeting AChE1 from Anopheles gambiae (AgAChE1), the malaria-transmitting mosquito, and for selectivity relative to the vertebrate Mus musculus AChE (mAChE). We show that

SUBMITTER: Kumari R 

PROVIDER: S-EPMC11474975 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature