ArticleNature communications2026
Structural and dynamic studies uncover a distinct allosteric modulatory site at the µ-opioid receptor.
Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
2 citing papers in PubMed.
- Structure-guided allosteric modulation of the delta opioid receptor.Nature communications · 2026Article
- Effects of two structurally diverse positive allosteric modulators on signaling bias at the μ-opioid receptor.Molecular pharmacology · 2025Article
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Authors and funding
12 authors.
Funding
Abstract
Positive allosteric modulators (PAMs) of the μ opioid receptor (MOR) offer a promising path toward safer opioid therapeutics, yet their mechanisms of action remain poorly understood. Here, we uncover the structural and mechanistic basis of BMS-986187, a chemically distinct MOR PAM with in vivo efficacy, using an integrated approach combining cryogenic electron microscopy (cryo-EM), molecular dynamics (MD) simulations, signaling assays, and site-directed mutagenesis. We identify a previously uncharacterized allosteric site for BMS-986187, a lipid-facing pocket formed by MOR transmembrane helices 2, 3, and 4, distinct from sites occupied by other known MOR PAMs or negative allosteric modulators. BMS-986187 engages both receptor residues and a neighboring cholesterol molecule, suggesting a cooperative ligand-lipid mechanism. Our studies pinpoint residues essential for allosteric modulation, while information-theory analysis of MD trajectories uncovers specific allosteric communication pathways linking the PAM site to both the orthosteric agonist DAMGO and the G protein interface. Together, these findings redefine the landscape of MOR allosteric modulation by revealing a previously unknown binding site, a potentially lipid-sensitive allosteric mechanism, and the molecular wiring of long-range communication within MOR. This work provides a molecular framework for the rational design of PAMs targeting opioid receptors with improved precision and possible therapeutic potential.
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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.