Characterization of binding kinetics and intracellular signaling of new psychoactive substances targeting cannabinoid receptor using transition-based reweighting method.

ABSTRACT: New psychoactive substances (NPS) targeting human cannabinoid receptor 1 pose a significant threat to society as recreational abusive drugs that have pronounced physiological side effects. These greater adverse effects compared to classical cannabinoids have been linked to the higher downstream β-arrestin signaling. Thus, understanding the mechanism of differential signaling will reveal an important structure-activity relationship essential for identifying and potentially regulating NPS molecules. In this study, we simulate the slow (un)binding process of NPS MDMB-Fubinaca and classical cannabinoid HU-210 from CB₁ using multi-ensemble simulation to decipher the effects of ligand binding dynamics on downstream signaling. The transition-based reweighing method is used for t

SUBMITTER: Dutta S 

PROVIDER: S-EPMC12582568 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature