A Putative Binding Model of Nitazene Derivatives at the <i>μ</i>-Opioid Receptor.

ABSTRACT: Nitazenes are a class of novel synthetic opioids with exceptionally high potency. Currently, an experimental structure of μOR-opioid receptor (μOR) in complex with a nitazene is lacking. Here we used a suite of computational tools, including consensus docking, conventional molecular dynamics (MD) and metadynamics simulations, to investigate the μOR binding modes of nitro-containing meto-, eto-, proto-, buto-, and isotonitazenes and nitro-less analogs, metodes-, etodes-, and protodesnitazenes. Docking generated three binding modes, whereby the nitro-substituted or unsubstituted benzimidazole group extends into SP1 (subpocket 1 between transmembrane helix or TM 2 and 3), SP2 (subpocket 2 between TM1, TM2, and TM7) or SP3 (subpocket 3 between TM5 and TM6). Simulations sug

SUBMITTER: Clayton J 

PROVIDER: S-EPMC11844390 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature