ArticleThe journal of physical chemistry. B2009
General anesthetic binding to neuronal alpha4beta2 nicotinic acetylcholine receptor and its effects on global dynamics.
Article in The journal of physical chemistry. B, 2009. 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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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.
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Who cites it
26 citing papers in PubMed, 35 citations in OpenAlex.
- General anesthetic modulation of a pentameric ligand-gated ion channel explored with simulations.Biophysical journal · 2026Article
- Alchemical Free Energy Calculations on Membrane-Associated Proteins.Journal of chemical theory and computation · 2023Review
- Effects of General Anesthetics on Synaptic Transmission and Plasticity.Current neuropharmacology · 2022Review
- Ion Channels in Anesthesia.Advances in experimental medicine and biology · 2021Article
- Open-channel blocking action of volatile anaesthetics desflurane and sevoflurane on human voltage-gated KBritish journal of pharmacology · 2020Article
- Propofol inhibits the voltage-gated sodium channel NaChBac at multiple sites.The Journal of general physiology · 2018Article
- Ketamine Inhibition of the Pentameric Ligand-Gated Ion Channel GLIC.Biophysical journal · 2017Article
- Heteromeric α7β2 Nicotinic Acetylcholine Receptors in the Brain.Trends in pharmacological sciences · 2016Review
- Direct Pore Binding as a Mechanism for Isoflurane Inhibition of the Pentameric Ligand-gated Ion Channel ELIC.Scientific reports · 2015Article
- Atomistic models of general anesthetics for use in in silico biological studies.The journal of physical chemistry. B · 2014Article
- Pentameric Ligand-gated Ion Channels : Insights from Computation.Molecular simulation · 2014Article
- Paying attention to smell: cholinergic signaling in the olfactory bulb.Frontiers in synaptic neuroscience · 2014Review
- Insights into distinct modulation of α7 and α7β2 nicotinic acetylcholine receptors by the volatile anesthetic isoflurane.The Journal of biological chemistry · 2013Article
- NMR resolved multiple anesthetic binding sites in the TM domains of the α4β2 nAChR.Biochimica et biophysica acta · 2013Article
- GABA binding to an insect GABA receptor: a molecular dynamics and mutagenesis study.Biophysical journal · 2012Article
- General anesthetics predicted to block the GLIC pore with micromolar affinity.PLoS computational biology · 2012Article
- NMR structures of the transmembrane domains of the α4β2 nAChR.Biochimica et biophysica acta · 2012Article
- NMR structure and dynamics of a designed water-soluble transmembrane domain of nicotinic acetylcholine receptor.Biochimica et biophysica acta · 2012Article
- Isoflurane alters the structure and dynamics of GLIC.Biophysical journal · 2011Article
- Alcohol-binding sites in distinct brain proteins: the quest for atomic level resolution.Alcoholism, clinical and experimental research · 2011Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The neuronal alpha4beta2 nicotinic acetylcholine receptor (nAChR) is a target for general anesthetics. Currently available experimental structural information is inadequate to understand where anesthetics bind and how they modulate the receptor motions essential to function. Using our published open-channel structure model of alpha4beta2 nAChR, we identified and evaluated six amphiphilic interaction sites for the volatile anesthetic halothane via flexible ligand docking and subsequent 20-ns molecular dynamics simulations. Halothane binding energies ranged from -6.8 to -2.4 kcal/mol. The primary binding sites were located at the interface of extracellular and transmembrane domains, where halothane perturbed conformations of, and widened the gap among, the Cys loop, the beta1-beta2 loop, and the TM2-TM3 linker. The halothane with the highest binding affinity at the interface between the alpha4 and beta2 subunits altered interactions between the protein and nearby lipids by competing for hydrogen bonds. Gaussian network model analyses of the alpha4beta2 nAChR structures at the end of 20-ns simulations in the absence or presence of halothane revealed profound changes in protein residue mobility. The concerted motions critical to protein function were also perturbed considerably. Halothane's effect on protein dynamics was not confined to the residues adjacent to the binding sites, indicating an action on a more global scale.
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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.