ArticleJournal of chemical information and modeling2015
Molecular docking screening using agonist-bound GPCR structures: probing the A2A adenosine receptor.
Article in Journal of chemical information and modeling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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.
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Who cites it
27 citing papers in PubMed, 71 citations in OpenAlex.
- Identification of nanomolar adenosine ANature communications · 2025Article
- Ligand-Induced Biased Activation of GPCRs: Recent Advances and New Directions from In Silico Approaches.Molecules (Basel, Switzerland) · 2025Review
- Scaffold Hopping and Screening for Potent Small Molecule Agonists for GRP94: Implications to Alleviate ER Stress-Associated Pathogenesis.Molecular biotechnology · 2024Article
- Mind the Gap-Deciphering GPCR Pharmacology Using 3D Pharmacophores and Artificial Intelligence.Pharmaceuticals (Basel, Switzerland) · 2022Review
- 4-Heteroaryl Substituted Amino-3,5-Dicyanopyridines as New Adenosine Receptor Ligands: Novel Insights on Structure-Activity Relationships and Perspectives.Pharmaceuticals (Basel, Switzerland) · 2022Article
- The Pharmacological Potential of Adenosine AMolecules (Basel, Switzerland) · 2022Review
- Molecular Simulations and Drug Discovery of Adenosine Receptors.Molecules (Basel, Switzerland) · 2022Review
- Structure-based identification of dual ligands at the AJournal of cheminformatics · 2021Article
- Purinergic Signaling: Impact of GPCR Structures on Rational Drug Design.ChemMedChem · 2020Review
- A Taxicab geometry quantification system to evaluate the performance of in silico methods: a case study on adenosine receptors ligands.Journal of computer-aided molecular design · 2020Article
- Amino-3,5-Dicyanopyridines Targeting the Adenosine Receptors Ranging from Pan Ligands to Combined APharmaceuticals (Basel, Switzerland) · 2019Article
- Non-Nucleoside Agonists of the Adenosine Receptors: An Overview.Pharmaceuticals (Basel, Switzerland) · 2019Review
- Accelerating the Throughput of Affinity Mass Spectrometry-Based Ligand Screening toward a G Protein-Coupled Receptor.Analytical chemistry · 2019Article
- Recent Trends and Applications of Molecular Modeling in GPCR⁻Ligand Recognition and Structure-Based Drug Design.International journal of molecular sciences · 2018Review
- Docking Screens for Dual Inhibitors of Disparate Drug Targets for Parkinson's Disease.Journal of medicinal chemistry · 2018Article
- Breakthrough in GPCR Crystallography and Its Impact on Computer-Aided Drug Design.Methods in molecular biology (Clifton, N.J.) · 2018Article
- Exploring G Protein-Coupled Receptors (GPCRs) Ligand Space via Cheminformatics Approaches: Impact on Rational Drug Design.Frontiers in pharmacology · 2018Review
- Bitopic fluorescent antagonists of the AMedChemComm · 2017Article
- Structural Probing and Molecular Modeling of the A₃ Adenosine Receptor: A Focus on Agonist Binding.Molecules (Basel, Switzerland) · 2017Review
- Recent Advances and Applications of Molecular Docking to G Protein-Coupled Receptors.Molecules (Basel, Switzerland) · 2017Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Crystal structures of G protein-coupled receptors (GPCRs) have recently revealed the molecular basis of ligand binding and activation, which has provided exciting opportunities for structure-based drug design. The A2A adenosine receptor (A2AAR) is a promising therapeutic target for cardiovascular diseases, but progress in this area is limited by the lack of novel agonist scaffolds. We carried out docking screens of 6.7 million commercially available molecules against active-like conformations of the A2AAR to investigate whether these structures could guide the discovery of agonists. Nine out of the 20 predicted agonists were confirmed to be A2AAR ligands, but none of these activated the ARs. The difficulties in discovering AR agonists using structure-based methods originated from limited atomic-level understanding of the activation mechanism and a chemical bias toward antagonists in the screened library. In particular, the composition of the screened library was found to strongly reduce the likelihood of identifying AR agonists, which reflected the high ligand complexity required for receptor activation. Extension of this analysis to other pharmaceutically relevant GPCRs suggested that library screening may not be suitable for targets requiring a complex receptor-ligand interaction network. Our results provide specific directions for the future development of novel A2AAR agonists and general strategies for structure-based drug discovery.
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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.