ArticleScientific reports2017
Dynamic and Kinetic Elements of µ-Opioid Receptor Functional Selectivity.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 56 citations in OpenAlex.
- Hold on tight: the kinetic profiling of opioid receptor ligands using the CORAL-MD.Journal of cheminformatics · 2026Article
- Elucidating zerumbone's low-efficacy agonism at the μ-opioid receptor via molecular dynamics simulation and Markov state modeling.Journal of computer-aided molecular design · 2025Article
- Total synthesis and biological activity of "carbamorphine": O-to-CHProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Structural Determinants of Buprenorphine Partial Agonism at the μ-Opioid Receptor.Journal of chemical information and modeling · 2025Article
- Evidencing the role of a conserved polar signaling channel in the activation mechanism of the μ-opioid receptor.Computational and structural biotechnology journal · 2025Article
- Cyclopamine modulates smoothened receptor activity in a binding position dependent manner.Communications biology · 2024Article
- Binding Position Dependent Modulation of Smoothened Activity by Cyclopamine.bioRxiv : the preprint server for biology · 2024Article
- IUPHAR themed review: Opioid efficacy, bias, and selectivity.Pharmacological research · 2023Review
- Dynamics of the Apo µ-Opioid Receptor in Complex with Gi Protein.International journal of molecular sciences · 2023Article
- Article
- Computational insights into ligand-induced G protein and β-arrestin signaling of the dopamine D1 receptor.Journal of computer-aided molecular design · 2023Article
- Activation mechanism of the human Smoothened receptor.Biophysical journal · 2023Article
- Molecular Basis of Inhibitory Mechanism of Naltrexone and Its Metabolites through Structural and Energetic Analyses.Molecules (Basel, Switzerland) · 2022Article
- Development of enhanced conformational sampling methods to probe the activation landscape of GPCRs.Advances in protein chemistry and structural biology · 2022Review
- Recent Molecular Insights into Agonist-specific Binding to the Mu-Opioid Receptor.Frontiers in molecular biosciences · 2022Review
- Encoding mu-opioid receptor biased agonism with interaction fingerprints.Journal of computer-aided molecular design · 2021Article
- Correlated Motions of Conserved Polar Motifs Lay out a Plausible Mechanism of G Protein-Coupled Receptor Activation.Biomolecules · 2021Article
- Allosteric communication regulates ligand-specific GPCR activity.The FEBS journal · 2021Review
- Markov State Models to Elucidate Ligand Binding Mechanism.Methods in molecular biology (Clifton, N.J.) · 2021Review
- Exploring the activation pathway and GProceedings of the National Academy of Sciences of the United States of America · 2020Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
While the therapeutic effect of opioids analgesics is mainly attributed to µ-opioid receptor (MOR) activation leading to G protein signaling, their side effects have mostly been linked to β-arrestin signaling. To shed light on the dynamic and kinetic elements underlying MOR functional selectivity, we carried out close to half millisecond high-throughput molecular dynamics simulations of MOR bound to a classical opioid drug (morphine) or a potent G protein-biased agonist (TRV-130). Statistical analyses of Markov state models built using this large simulation dataset combined with information theory enabled, for the first time: a) Identification of four distinct metastable regions along the activation pathway, b) Kinetic evidence of a different dynamic behavior of the receptor bound to a classical or G protein-biased opioid agonist, c) Identification of kinetically distinct conformational states to be used for the rational design of functionally selective ligands that may eventually be developed into improved drugs; d) Characterization of multiple activation/deactivation pathways of MOR, and e) Suggestion from calculated transition timescales that MOR conformational changes are not the rate-limiting step in receptor activation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.