ArticleNature chemical biology2018
Structure-inspired design of β-arrestin-biased ligands for aminergic GPCRs.
Article in Nature chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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Who cites it
102 citing papers in PubMed.
- Steric control of signaling bias in the immunometabolic receptor GPR84.Nature communications · 2026Article
- Artificial intelligence and ultra-high performance computing methods and experiments for drug discovery: virtual screening, deep learning, molecular dynamics simulations, ADMET modelling, and experimental validation.Molecular biomedicine · 2026Review
- Mechanistic insight into signal bias by the agonist-dependent conformational dynamics of GPR84.Nature communications · 2026Article
- The Role of Intrinsically Disordered Domains in Regulating G Protein-Coupled Receptor Signaling.Journal of the American Chemical Society · 2026Article
- GPCR signaling systems facilitate precision interventions for multi-oncology therapy.Frontiers in systems biology · 2026Review
- Conformational Heterogeneity Underlying Divergent Signaling in Class A G Protein-Coupled Receptors.ACS pharmacology & translational science · 2025Review
- Transient ligand contacts of the intrinsically disordered N-terminus of neuropeptide YNature communications · 2025Article
- The role of intrinsically disordered domains in regulating G protein coupled receptor signaling.bioRxiv : the preprint server for biology · 2025Article
- Constitutively active orphan G protein-coupled receptors through the lenses of cryo-electron microscopy.The Journal of biological chemistry · 2025Review
- Residence time in drug discovery: current insights and future perspectives.Pharmacological reports : PR · 2025Review
- Ligand-Induced Biased Activation of GPCRs: Recent Advances and New Directions from In Silico Approaches.Molecules (Basel, Switzerland) · 2025Review
- Systematic analysis of biomolecular conformational ensembles with PENSA.The Journal of chemical physics · 2025Article
- Intracellular GPCR modulators enable precision pharmacology.npj drug discovery · 2025Review
- Structural Pharmacology of Bufotenine Derivatives in Activating the 5-HTResearch (Washington, D.C.) · 2025Article
- Biased Signaling Agonists Promote Distinct Phosphorylation and Conformational States of the Dopamine D3 Receptor.International journal of molecular sciences · 2024Article
- The Art and Science of Molecular Docking.Annual review of biochemistry · 2024Review
- Peptide-derived ligands for the discovery of safer opioid analgesics.Drug discovery today · 2024Review
- G protein-coupled receptors (GPCRs): advances in structures, mechanisms, and drug discovery.Signal transduction and targeted therapy · 2024Review
- Molecular basis of human trace amine-associated receptor 1 activation.Nature communications · 2024Article
- Biased Dopamine DBiomolecules & therapeutics · 2024Article
42 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors.
Funding
Abstract
Development of biased ligands targeting G protein-coupled receptors (GPCRs) is a promising approach for current drug discovery. Although structure-based drug design of biased agonists remains challenging even with an abundance of GPCR crystal structures, we present an approach for translating GPCR structural data into β-arrestin-biased ligands for aminergic GPCRs. We identified specific amino acid-ligand contacts at transmembrane helix 5 (TM5) and extracellular loop 2 (EL2) responsible for Gi/o and β-arrestin signaling, respectively, and targeted those residues to develop biased ligands. For these ligands, we found that bias is conserved at other aminergic GPCRs that retain similar residues at TM5 and EL2. Our approach provides a template for generating arrestin-biased ligands by modifying predicted ligand interactions that block TM5 interactions and promote EL2 interactions. This strategy may facilitate the structure-guided design of arrestin-biased ligands at other GPCRs, including polypharmacological biased ligands.
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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.