ArticleBiophysical journal2011
Microsecond simulations indicate that ethanol binds between subunits and could stabilize an open-state model of a glycine receptor.
Article in Biophysical journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 72 citations in OpenAlex.
- General anesthetic modulation of a pentameric ligand-gated ion channel explored with simulations.Biophysical journal · 2026Article
- Single nucleotide variants inBiochemistry and biophysics reports · 2026Article
- Positive Allosteric Modulators of Glycine Receptors and Their Potential Use in Pain Therapies.Pharmacological reviews · 2022Review
- Effect of ethanol on Munc13-1 C1 in Membrane: A Molecular Dynamics Simulation Study.Alcoholism, clinical and experimental research · 2020Article
- Menthol Binding to the Human α4β2 Nicotinic Acetylcholine Receptor Facilitated by Its Strong Partitioning in the Membrane.The journal of physical chemistry. B · 2020Article
- Allosteric potentiation of a ligand-gated ion channel is mediated by access to a deep membrane-facing cavity.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Pharmacological characterization of the neurotrophic sesquiterpene jiadifenolide reveals a non-convulsant signature and potential for progression in neurodegenerative disease studies.Biochemical pharmacology · 2018Article
- The neural γJournal of molecular modeling · 2018Article
- Permeating disciplines: Overcoming barriers between molecular simulations and classical structure-function approaches in biological ion transport.Biochimica et biophysica acta. Biomembranes · 2018Review
- Computational membrane biophysics: From ion channel interactions with drugs to cellular function.Biochimica et biophysica acta. Proteins and proteomics · 2017Review
- Ketamine Inhibition of the Pentameric Ligand-Gated Ion Channel GLIC.Biophysical journal · 2017Article
- The cellular membrane as a mediator for small molecule interaction with membrane proteins.Biochimica et biophysica acta · 2016Article
- All the O2 Consumed by Thermus thermophilus Cytochrome ba3 Is Delivered to the Active Site through a Long, Open Hydrophobic Tunnel with Entrances within the Lipid Bilayer.Biochemistry · 2016Article
- Critical needs in drug discovery for cessation of alcohol and nicotine polysubstance abuse.Progress in neuro-psychopharmacology & biological psychiatry · 2016Review
- Inter- and Intra-Subunit Butanol/Isoflurane Sites of Action in the Human Glycine Receptor.Frontiers in molecular neuroscience · 2016Article
- Microscopic Characterization of Membrane Transporter Function by In Silico Modeling and Simulation.Methods in enzymology · 2016Review
- Anesthetics target interfacial transmembrane sites in nicotinic acetylcholine receptors.Neuropharmacology · 2015Review
- Article
- Atomistic insights into human Cys-loop receptors by solution NMR.Biochimica et biophysica acta · 2015Article
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Cys-loop receptors constitute a superfamily of ion channels gated by ligands such as acetylcholine, serotonin, glycine, and γ-aminobutyric acid. All of these receptors are thought to share structural characteristics, but due to high sequence variation and limited structure availability, our knowledge about allosteric binding sites is still limited. These sites are frequent targets of anesthetic and alcohol molecules, and are of high pharmacological importance. We used molecular simulations to study ethanol binding and equilibrium exchange for the homomeric α1 glycine receptor (GlyRα1), modeled on the structure of the Gloeobacter violaceus pentameric ligand-gated channel. Ethanol has a well-known potentiating effect and can be used in high concentrations. By performing two microsecond-scale simulations of GlyR with/without ethanol, we were able to observe spontaneous binding in cavities and equilibrium ligand exchange. Of interest, it appears that there are ethanol-binding sites both between and within the GlyR transmembrane subunits, with the intersubunit site having the highest occupancy and slowest exchange (∼200 ns). This model site involves several residues that were previously identified via mutations as being crucial for potentiation. Finally, ethanol appears to stabilize the GlyR model built on a presumably open form of the ligand-gated channel. This stabilization could help explain the effects of allosteric ligand binding in Cys-loop receptors.
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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.