ArticleACS chemical biology2016
Proposed Mode of Binding and Action of Positive Allosteric Modulators at Opioid Receptors.
Article in ACS chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 77 citations in OpenAlex.
- Structure-guided allosteric modulation of the delta opioid receptor.Nature communications · 2026Article
- Molecular mechanism of allosteric modulation of opioid receptors.Signal transduction and targeted therapy · 2026Article
- Identification of Subtype-Selective Binding Sites in the Opioid Receptor Family.Journal of chemical information and modeling · 2026Article
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- Identification of 1,3,8-Triazaspiro[4.5]Decane-2,4-Dione Derivatives as a NovelThe Journal of pharmacology and experimental therapeutics · 2024Article
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- Interaction of Synthetic Cannabinoid Receptor Agonists with Cannabinoid Receptor I: Insights into Activation Molecular Mechanism.International journal of molecular sciences · 2023Article
- Inner pore hydration free energy controls the activation of big potassium channels.Biophysical journal · 2023Article
- Deep Learning Dynamic Allostery of G-Protein-Coupled Receptors.Research square · 2023Article
- Deep Learning Dynamic Allostery of G-Protein-Coupled Receptors.bioRxiv : the preprint server for biology · 2023Article
- Allosteric Modulators of Dopamine DMolecules (Basel, Switzerland) · 2022Review
- Using Metadynamics To Explore the Free Energy of Dewetting in Biologically Relevant Nanopores.The journal of physical chemistry. B · 2022Article
- Fly casting with ligand sliding and orientational selection supporting complex formation of a GPCR and a middle sized flexible molecule.Scientific reports · 2022Article
- Biased, Bitopic, Opioid-Adrenergic Tethered Compounds May Improve Specificity, Lower Dosage and Enhance Agonist or Antagonist Function with Reduced Risk of Tolerance and Addiction.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Metadynamics simulations leveraged by statistical analyses and artificial intelligence-based tools to inform the discovery of G protein-coupled receptor ligands.Frontiers in endocrinology · 2022Review
- Article
- Identification of a Novel Delta Opioid Receptor Agonist Chemotype with Potential Negative Allosteric Modulator Capabilities.Molecules (Basel, Switzerland) · 2021Article
- Binding free energy decomposition and multiple unbinding paths of buried ligands in a PreQ1 riboswitch.PLoS computational biology · 2021Article
- Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Available crystal structures of opioid receptors provide a high-resolution picture of ligand binding at the primary ("orthosteric") site, that is, the site targeted by endogenous ligands. Recently, positive allosteric modulators of opioid receptors have also been discovered, but their modes of binding and action remain unknown. Here, we use a metadynamics-based strategy to efficiently sample the binding process of a recently discovered positive allosteric modulator of the δ-opioid receptor, BMS-986187, in the presence of the orthosteric agonist SNC-80, and with the receptor embedded in an explicit lipid-water environment. The dynamics of BMS-986187 were enhanced by biasing the potential acting on the ligand-receptor distance and ligand-receptor interaction contacts. Representative lowest-energy structures from the reconstructed free-energy landscape revealed two alternative ligand binding poses at an allosteric site delineated by transmembrane (TM) helices TM1, TM2, and TM7, with some participation of TM6. Mutations of amino acid residues at these proposed allosteric sites were found to either affect the binding of BMS-986187 or its ability to modulate the affinity and/or efficacy of SNC-80. Taken together, these combined experimental and computational studies provide the first atomic-level insight into the modulation of opioid receptor binding and signaling by allosteric modulators.
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What OpenQuestion holds
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.