ArticleJournal of computer-aided molecular design2015
Modeling ligand recognition at the P2Y12 receptor in light of X-ray structural information.
Article in Journal of computer-aided molecular design, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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
19 citing papers in PubMed.
- Prasugrel Intermediate Metabolite Modulates Platelet Inhibition by Negatively Interfering With an Active Metabolite: An Ex Vivo, In Vitro, and In Silico Study.Arteriosclerosis, thrombosis, and vascular biology · 2025Trial
- Structuring Disorder via Supervised Molecular Dynamics: Uncovering Arginine-Glycine-Glycine-Mediated Ribonucleic Acid-Intrinsically Disordered Region Recognition Mechanisms.Journal of chemical information and modeling · 2026Article
- Exploration of Fluorinated Pyrazolidine-3,5-Diones for Positron Emission Tomography Imaging of the P2YChemMedChem · 2025Article
- Drug-like Antagonists of P2Y Receptor Subtypes: An Update.Journal of medicinal chemistry · 2025Review
- Chimeras Derived from a P2YACS pharmacology & translational science · 2024Article
- Pharmacological characterization of P2Y receptor subtypes - an update.Purinergic signalling · 2024Review
- Ticagrelor inverse agonist activity at the P2YBritish journal of pharmacology · 2024Article
- Unlocking the Conformational Changes of P2YMolecules (Basel, Switzerland) · 2023Article
- Investigating RNA-protein recognition mechanisms through supervised molecular dynamics (SuMD) simulations.NAR genomics and bioinformatics · 2022Article
- Medicinal chemistry of P2 and adenosine receptors: Common scaffolds adapted for multiple targets.Biochemical pharmacology · 2021Review
- Membrane Environment Modulates Ligand-Binding Propensity of P2Y12 Receptor.Pharmaceutics · 2021Article
- In Silico Drug Design for Purinergic GPCRs: Overview on Molecular Dynamics Applied to Adenosine and P2Y Receptors.Biomolecules · 2020Review
- Molecular Modeling Applied to the Discovery of New Lead Compounds for P2 Receptors Based on Natural Sources.Frontiers in pharmacology · 2020Review
- Utilization of Biased G Protein-Coupled ReceptorSignaling towards Development of Safer andPersonalized Therapeutics.Molecules (Basel, Switzerland) · 2019Review
- Coupling Supervised Molecular Dynamics (SuMD) with Entropy Estimations To Shine Light on the Stability of Multiple Binding Sites.ACS medicinal chemistry letters · 2019Article
- Designing Hybrids Targeting the Cholinergic System by Modulating the Muscarinic and Nicotinic Receptors: A Concept to Treat Alzheimer's Disease.Molecules (Basel, Switzerland) · 2018Review
- Breakthrough in GPCR Crystallography and Its Impact on Computer-Aided Drug Design.Methods in molecular biology (Clifton, N.J.) · 2018Article
- Article
- Medicinal chemistry of adenosine, P2Y and P2X receptors.Neuropharmacology · 2016Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
The G protein-coupled P2Y12 receptor (P2Y12R) is an important antithrombotic target and of great interest for pharmaceutical discovery. Its recently solved, highly divergent crystallographic structures in complex either with nucleotides (full or partial agonist) or with a nonnucleotide antagonist raise the question of which structure is more useful to understand ligand recognition. Therefore, we performed extensive molecular modeling studies based on these structures and mutagenesis, to predict the binding modes of major classes of P2Y12R ligands previously reported. Various nucleotide derivatives docked readily to the agonist-bound P2Y12R, but uncharged nucleotide-like antagonist ticagrelor required a hybrid receptor resembling the agonist-bound P2Y12R except for the top portion of TM6. Supervised molecular dynamics (SuMD) of ticagrelor binding indicated interactions with the extracellular regions of P2Y12R, defining possible meta-binding sites. Ureas, sulfonylureas, sulfonamides, anthraquinones and glutamic acid piperazines docked readily to the antagonist-bound P2Y12R. Docking dinucleotides at both agonist- and antagonist-bound structures suggested interactions with two P2Y12R pockets. Thus, our structure-based approach consistently rationalized the main structure-activity relationships within each ligand class, giving useful information for designing improved ligands.
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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.