ArticlePloS one2014
Structural and energetic effects of A2A adenosine receptor mutations on agonist and antagonist binding.
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 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 56 citations in OpenAlex.
- BindFlow: A Free, User-Friendly Pipeline for Absolute Binding Free Energy Calculations Using Free Energy Perturbation or MM(PB/GB)SA.Journal of chemical theory and computation · 2026Article
- AMarine drugs · 2025Article
- Accurate predictions of protein mutational effects accelerated with a hybrid-topology free energy protocol.Communications chemistry · 2025Article
- Anticancer Activity of Triterpene Glycosides Cucumarioside AInternational journal of molecular sciences · 2025Article
- Ligand and Residue Free Energy Perturbations Solve the Dual Binding Mode Proposal for an AThe journal of physical chemistry. B · 2025Article
- Alchemical Free Energy Calculations on Membrane-Associated Proteins.Journal of chemical theory and computation · 2023Review
- Molecular Simulations and Drug Discovery of Adenosine Receptors.Molecules (Basel, Switzerland) · 2022Review
- Deciphering conformational selectivity in the A2A adenosine G protein-coupled receptor by free energy simulations.PLoS computational biology · 2021Article
- Identification of V6.51L as a selectivity hotspot in stereoselective AScientific reports · 2021Article
- Structural Basis of Inhibition of Human Insulin-Regulated Aminopeptidase (IRAP) by Benzopyran-Based Inhibitors.Frontiers in molecular biosciences · 2021Article
- Free Energy Calculations for Protein-Ligand Binding Prediction.Methods in molecular biology (Clifton, N.J.) · 2021Review
- Thermodynamics and Kinetics of Drug-Target Binding by Molecular Simulation.Chemical reviews · 2020Review
- X-Ray Crystallography and Free Energy Calculations Reveal the Binding Mechanism of AAngewandte Chemie (International ed. in English) · 2020Article
- In Silico Drug Design for Purinergic GPCRs: Overview on Molecular Dynamics Applied to Adenosine and P2Y Receptors.Biomolecules · 2020Review
- Evolution of Angiotensin Peptides and Peptidomimetics as Angiotensin II Receptor Type 2 (AT2) Receptor Agonists.Biomolecules · 2020Article
- Insights into adenosine A2A receptor activation through cooperative modulation of agonist and allosteric lipid interactions.PLoS computational biology · 2020Article
- QligFEP: an automated workflow for small molecule free energy calculations in Q.Journal of cheminformatics · 2019Article
- Recent Trends and Applications of Molecular Modeling in GPCR⁻Ligand Recognition and Structure-Based Drug Design.International journal of molecular sciences · 2018Review
- Design, synthesis and evaluation of 2-aryl benzoxazoles as promising hit for the AJournal of enzyme inhibition and medicinal chemistry · 2017Article
- Structure-Based Design of Potent and Selective Ligands at the Four Adenosine Receptors.Molecules (Basel, Switzerland) · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To predict structural and energetic effects of point mutations on ligand binding is of considerable interest in biochemistry and pharmacology. This is not only useful in connection with site-directed mutagenesis experiments, but could also allow interpretation and prediction of individual responses to drug treatment. For G-protein coupled receptors systematic mutagenesis has provided the major part of functional data as structural information until recently has been very limited. For the pharmacologically important A(2A) adenosine receptor, extensive site-directed mutagenesis data on agonist and antagonist binding is available and crystal structures of both types of complexes have been determined. Here, we employ a computational strategy, based on molecular dynamics free energy simulations, to rationalize and interpret available alanine-scanning experiments for both agonist and antagonist binding to this receptor. These computer simulations show excellent agreement with the experimental data and, most importantly, reveal the molecular details behind the observed effects which are often not immediately evident from the crystal structures. The work further provides a distinct validation of the computational strategy used to assess effects of point-mutations on ligand binding. It also highlights the importance of considering not only protein-ligand interactions but also those mediated by solvent water molecules, in ligand design projects.
Indexed as
Identifiers
What OpenQuestion holds
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.