ArticlePLoS computational biology2020
Insights into adenosine A2A receptor activation through cooperative modulation of agonist and allosteric lipid interactions.
Article in PLoS computational biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- Atomistic insights into the magnetic-field modulation of the [Formula: see text] adenosine receptor.Scientific reports · 2026Article
- Unraveling allosteric signaling of G protein-coupled receptors (GPCRs) by single-molecule fluorescence.Biophysical reviews · 2026Review
- General structure-activity relationship models for the inhibitors of Adenosine receptors: A machine learning approach.Molecular diversity · 2025Article
- Review of Preclinical and Clinical Studies Supporting the Role of Polydeoxyribonucleotide in the Treatment of Tendon Disorders.Medical science monitor : international medical journal of experimental and clinical research · 2025Review
- Large scale investigation of GPCR molecular dynamics data uncovers allosteric sites and lateral gateways.Nature communications · 2025Article
- Exploring the pharmacological mechanisms for alleviating OSA: Adenosine A2A receptor downregulation of the PI3K/Akt/HIF‑1 pathway (Review).Biomedical reports · 2025Review
- Mechanical stress and anionic lipids synergistically stabilize an atypical structure of the angiotensin II type 1 receptor (AT1).PLoS computational biology · 2024Article
- Anionic phospholipids control mechanisms of GPCR-G protein recognition.Nature communications · 2023Article
- Anionic Phospholipids Control Mechanisms of GPCR-G Protein Recognition.bioRxiv : the preprint server for biology · 2023Article
- Allosteric Modulators of Dopamine DMolecules (Basel, Switzerland) · 2022Review
- Evaluating Allosteric Perturbations in Cannabinoid Receptor 1 byACS omega · 2022Article
- Intermolecular Interactions in G Protein-Coupled Receptor Allosteric Sites at the Membrane Interface from Molecular Dynamics Simulations and Quantum Chemical Calculations.Journal of chemical information and modeling · 2022Article
- SINAPs: A Software Tool for Analysis and Visualization of Interaction Networks of Molecular Dynamics Simulations.Journal of chemical information and modeling · 2022Article
- Molecular Simulations and Drug Discovery of Adenosine Receptors.Molecules (Basel, Switzerland) · 2022Review
- Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Insights into the Role of Membrane Lipids in the Structure, Function and Regulation of Integral Membrane Proteins.International journal of molecular sciences · 2021Review
- Lipids and Phosphorylation Conjointly Modulate Complex Formation of βFrontiers in cell and developmental biology · 2021Article
- Dynamical Correlations Reveal Allosteric Sites in G Protein-Coupled Receptors.International journal of molecular sciences · 2020Article
- Statistics for the analysis of molecular dynamics simulations: providing P values for agonist-dependent GPCR activation.Scientific reports · 2020Article
- Probing Membrane Protein Assembly into Nanodiscs by In Situ Dynamic Light Scattering: ABiology · 2020Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The activation process of G protein-coupled receptors (GPCRs) has been extensively studied, both experimentally and computationally. In particular, Molecular Dynamics (MD) simulations have proven useful in exploring GPCR conformational space. The typical behaviour of class A GPCRs, when subjected to unbiased MD simulations from their crystallized inactive state, is to fluctuate between inactive and intermediate(s) conformations, even with bound agonist. Fully active conformation(s) are rarely stabilized unless a G protein is also bound. Despite several crystal structures of the adenosine A2a receptor (A2aR) having been resolved in complex with co-crystallized agonists and Gs protein, its agonist-mediated activation process is still not completely understood. In order to thoroughly examine the conformational landscape of A2aR activation, we performed unbiased microsecond-length MD simulations in quadruplicate, starting from the inactive conformation either in apo or with bound agonists: endogenous adenosine or synthetic NECA, embedded in two homogeneous phospholipid membranes: 1,2-dioleoyl-sn-glycerol-3-phosphoglycerol (DOPG) or 1,2-dioleoyl-sn-glycerol-3-phosphocholine (DOPC). In DOPC with bound adenosine or NECA, we observe transition to an intermediate receptor conformation consistent with the known adenosine-bound crystal state. In apo state in DOPG, two different intermediate conformations are obtained. One is similar to that observed with bound adenosine in DOPC, while the other is closer to the active state but not yet fully active. Exclusively, in DOPG with bound adenosine or NECA, we reproducibly identify receptor conformations with fully active features, which are able to dock Gs protein. These different receptor conformations can be attributed to the action/absence of agonist and phospholipid-mediated allosteric effects on the intracellular side of the receptor.
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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.