ArticleScientific reports2018
Dopamine D3 receptor antagonist reveals a cryptic pocket in aminergic GPCRs.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 53 citations in OpenAlex.
- Developing the Dopamine D3 Receptor (D3R) Antagonist, (R)-VK4-116, as a Non-Opioid Medication for the Treatment of Opioid Use Disorder.Medicinal research reviews · 2026Review
- Design, synthesis, drug-likeness, and molecular dynamics evaluations of monobrominated amathamide G analogs as potential ligands for D2-like dopamine receptors.In silico pharmacology · 2026Article
- Molecular basis of ligand binding and receptor activation at the human ANature communications · 2025Article
- Recent computational advances in the identification of cryptic binding sites for drug discovery.Bioinformatics advances · 2025Review
- Multiple recent HCAR2 structures demonstrate a highly dynamic ligand binding and G protein activation mode.Nature communications · 2024Review
- Bioorthogonal Tethering Enhances Drug Fragment Affinity for G Protein-Coupled Receptors in Live Cells.Journal of the American Chemical Society · 2023Article
- Activation mechanism of the human Smoothened receptor.Biophysical journal · 2023Article
- Approach to the specificity and selectivity between D2 and D3 receptors by mutagenesis and binding experiments part I: Expression and characterization of D2 and D3 receptor mutants.Protein science : a publication of the Protein Society · 2022Article
- Mind the Gap-Deciphering GPCR Pharmacology Using 3D Pharmacophores and Artificial Intelligence.Pharmaceuticals (Basel, Switzerland) · 2022Review
- The Impact of the Secondary Binding Pocket on the Pharmacology of Class A GPCRs.Frontiers in pharmacology · 2022Review
- Potential Mechanisms for Why Not All Antipsychotics Are Able to Occupy Dopamine DFrontiers in psychiatry · 2022Review
- Evidence for Two Modes of Binding of the Negative Allosteric Modulator SB269,652 to the Dopamine DBiomedicines · 2021Article
- Activation pathway of a G protein-coupled receptor uncovers conformational intermediates as targets for allosteric drug design.Nature communications · 2021Article
- How Do Molecular Dynamics Data Complement Static Structural Data of GPCRs.International journal of molecular sciences · 2020Review
- Computational insights into the molecular mechanisms of differentiated allosteric modulation at the mu opioid receptor by structurally similar bitopic modulators.Journal of computer-aided molecular design · 2020Article
- Investigating Cryptic Binding Sites by Molecular Dynamics Simulations.Accounts of chemical research · 2020Review
- Cryptic pocket formation underlies allosteric modulator selectivity at muscarinic GPCRs.Nature communications · 2019Article
- Molecular Dynamics Simulations of the Allosteric Modulation of the Adenosine A2A Receptor by a Mini-G Protein.Scientific reports · 2019Article
- Insights From Molecular Dynamics Simulations of a Number of G-Protein Coupled Receptor Targets for the Treatment of Pain and Opioid Use Disorders.Frontiers in molecular neuroscience · 2019Review
- Inclusion of enclosed hydration effects in the binding free energy estimation of dopamine D3 receptor complexes.PloS one · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The recent increase in the number of X-ray crystal structures of G-protein coupled receptors (GPCRs) has been enabling for structure-based drug design (SBDD) efforts. These structures have revealed that GPCRs are highly dynamic macromolecules whose function is dependent on their intrinsic flexibility. Unfortunately, the use of static structures to understand ligand binding can potentially be misleading, especially in systems with an inherently high degree of conformational flexibility. Here, we show that docking a set of dopamine D3 receptor compounds into the existing eticlopride-bound dopamine D3 receptor (D3R) X-ray crystal structure resulted in poses that were not consistent with results obtained from site-directed mutagenesis experiments. We overcame the limitations of static docking by using large-scale high-throughput molecular dynamics (MD) simulations and Markov state models (MSMs) to determine an alternative pose consistent with the mutation data. The new pose maintains critical interactions observed in the D3R/eticlopride X-ray crystal structure and suggests that a cryptic pocket forms due to the shift of a highly conserved residue, F
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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.