Elucidating zerumbone's low-efficacy agonism at the μ-opioid receptor via molecular dynamics simulation and Markov state modeling.

ABSTRACT: Zerumbone is a natural sesquiterpene compound from Zingiber zerumbet plant. While it significantly exhibits analgesic properties through the μ-opioid receptor (μOR) found in animal models, its precise molecular mechanism at the receptor level remains poorly investigated. The present work involves 1-µs molecular dynamics (MD) simulations, MM/PBSA binding-free energy analyses, principal component analysis (PCA) as well as Markov state modeling (MSM) to address how the dynamic basis of zerumbone-μOR interactions compared to morphine, which is a known full agonist. MD trajectories reported greater receptor backbone fluctuations, improved loop mobility, reduced stable hydrogen bonds, and moderate receptor compaction in the zerumbone-bound state in contrast to morphine. MM/PBSA calculations indi

SUBMITTER: Ayub WMW 

PROVIDER: S-EPMC12552253 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature