Structural Basis for Molecular Recognition of Cannabinoids by Inhibitory Cys-Loop Channels.
Journal of medicinal chemistry March 14, 2024 Lautaro D Alvarez, N R Carina Alves 7 citations
Cannabinoids from Cannabis sativa interact with human proteins called Cys-loop receptors, which mediate inhibitory signals in the nervous system. The binding sites for cannabinoids on these receptors are located within the transmembrane domain, but their exact positions have remained unknown for over a decade. This Perspective describes the computational methods used to identify these binding sites, including analysis of recently resolved cryo-EM structures of zebrafish glycine receptors bound to Δ9-tetrahydrocannabinol and molecular dynamics simulations of the THC-GlyR complex. The work aims to guide future studies on the molecular basis of cannabinoid action on inhibitory channels.