ArticlePloS one2014
Active-state model of a dopamine D2 receptor-Gαi complex stabilized by aripiprazole-type partial agonists.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Place of the partial dopamine receptor agonist aripiprazole in the management of schizophrenia in adults: a Delphi consensus study.BMC psychiatry · 2022Pooled it
- A structural overview of G-protein-coupled receptors in neurological disorders.Acta pharmacologica Sinica · 2026Review
- QT Interval, Antipsychotics and Correlates Among Patients with Schizophrenia: Cross-Sectional Data from the Multicentric Real-World FACE-SZ.Drug safety · 2025Article
- Identification of Novel Dopamine DMolecules (Basel, Switzerland) · 2022Article
- Allosteric modulation of dopamine DPharmacological reports : PR · 2022Article
- Ligand-directed bias of G protein signaling at the dopamine DCell chemical biology · 2022Article
- Interactions of a boron-containing levodopa derivative on DJournal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2022Article
- Enhancing the Signaling of GPCRs via Orthosteric Ions.ACS central science · 2020Article
- Preferential Coupling of Dopamine DInternational journal of molecular sciences · 2020Article
- A Machine Learning Approach for the Discovery of Ligand-Specific Functional Mechanisms of GPCRs.Molecules (Basel, Switzerland) · 2019Article
- A Complete Assessment of Dopamine Receptor- Ligand Interactions through Computational Methods.Molecules (Basel, Switzerland) · 2019Article
- Structure-inspired design of β-arrestin-biased ligands for aminergic GPCRs.Nature chemical biology · 2018Article
- Investigating allosteric effects on the functional dynamics of β2-adrenergic ternary complexes with enhanced-sampling simulations.Chemical science · 2017Article
- Comparative MD Simulations Indicate a Dual Role for Arg1323.50 in Dopamine-Dependent D2R Activation.PloS one · 2016Article
- Update on the Mechanism of Action of Aripiprazole: Translational Insights into Antipsychotic Strategies Beyond Dopamine Receptor Antagonism.CNS drugs · 2015Review
- Immunotoxicological Effects of Aripiprazole: In vivo and In vitro Studies.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2015Article
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Partial agonists exhibit a submaximal capacity to enhance the coupling of one receptor to an intracellular binding partner. Although a multitude of studies have reported different ligand-specific conformations for a given receptor, little is known about the mechanism by which different receptor conformations are connected to the capacity to activate the coupling to G-proteins. We have now performed molecular-dynamics simulations employing our recently described active-state homology model of the dopamine D2 receptor-Gαi protein-complex coupled to the partial agonists aripiprazole and FAUC350, in order to understand the structural determinants of partial agonism better. We have compared our findings with our model of the D2R-Gαi-complex in the presence of the full agonist dopamine. The two partial agonists are capable of inducing different conformations of important structural motifs, including the extracellular loop regions, the binding pocket and, in particular, intracellular G-protein-binding domains. As G-protein-coupling to certain intracellular epitopes of the receptor is considered the key step of allosterically triggered nucleotide-exchange, it is tempting to assume that impaired coupling between the receptor and the G-protein caused by distinct ligand-specific conformations is a major determinant of partial agonist efficacy.
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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.