ArticleChemical biology & drug design2014
Mapping of allosteric druggable sites in activation-associated conformers of the M2 muscarinic receptor.
Article in Chemical biology & drug design, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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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.
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Who cites it
26 citing papers in PubMed, 50 citations in OpenAlex.
- Uncovering hidden druggable sites: computational approaches to allosteric and cryptic pocket discovery-from molecular dynamics to AI.Journal of computer-aided molecular design · 2026Review
- Mechanism of GPR84 allosteric modulation at a helix 8-proximate site.Science advances · 2026Article
- Visualizing agonist-induced M2 receptor activation regulated by aromatic ring dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Application of Mixed-Solvent Molecular Dynamics Simulations for Prediction of Allosteric Sites on G Protein-Coupled Receptors.Molecular pharmacology · 2023Article
- Allosteric Regulation of G-Protein-Coupled Receptors: From Diversity of Molecular Mechanisms to Multiple Allosteric Sites and Their Ligands.International journal of molecular sciences · 2023Review
- Conservation of Allosteric Ligand Binding Sites in G-Protein Coupled Receptors.Journal of chemical information and modeling · 2022Article
- Mapping the binding sites of challenging drug targets.Current opinion in structural biology · 2022Review
- Unravelling the molecular interactions between the SARS-CoV-2 RBD spike protein and various specific monoclonal antibodies.Biochimie · 2022Article
- IgG1-b12-HIV-gp120 Interface in Solution: A Computational Study.Journal of chemical information and modeling · 2022Article
- Computational Methods for Structure-Based Drug Design Through System Biology.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Probe Confined Dynamic Mapping for G Protein-Coupled Receptor Allosteric Site Prediction.ACS central science · 2021Article
- Dynamical important residue network (DIRN): network inference via conformational change.Bioinformatics (Oxford, England) · 2019Article
- Analysis of tractable allosteric sites in G protein-coupled receptors.Scientific reports · 2019Article
- Intracellular Receptor Modulation: Novel Approach to Target GPCRs.Trends in pharmacological sciences · 2018Review
- Ensemble docking to difficult targets in early-stage drug discovery: Methodology and application to fibroblast growth factor 23.Chemical biology & drug design · 2018Article
- Mapping the allosteric sites of the AChemical biology & drug design · 2018Article
- Identification of a Different Agonist-Binding Site and Activation Mechanism of the Human P2YScientific reports · 2017Article
- Leveraging allostery to improve G protein-coupled receptor (GPCR)-directed therapeutics: cannabinoid receptor 1 as discovery target.Expert opinion on drug discovery · 2016Review
- G-protein coupled receptors: advances in simulation and drug discovery.Current opinion in structural biology · 2016Review
- A computationally identified compound antagonizes excess FGF-23 signaling in renal tubules and a mouse model of hypophosphatemia.Science signaling · 2016Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
G-protein-coupled receptors (GPCRs) are key cellular signaling proteins and have been targeted by approximately 30-40% of marketed drugs for treating many human diseases including cancer and heart failure. Recently, we directly observed activation of the M2 muscarinic receptor through long-timescale accelerated molecular dynamics (aMD) simulation, which revealed distinct inactive, intermediate and active conformers of the receptor. Here, FTMAP is applied to search for 'hot spots' in these activation-associated conformers using a library of 16 organic probe molecules that represent fragments of potential drugs. Seven allosteric (non-orthosteric) binding sites are identified in the M2 receptor through the FTMAP analysis. These sites are distributed in the solvent-exposed extracellular and intracellular mouth regions, as well as the lipid-exposed pockets formed by the transmembrane α helices TM3-TM4, TM5-TM6 and TM7-TM1/TM2. They serve as promising target sites for designing novel allosteric modulators as receptor-selective drugs.
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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.