ArticleThe journal of physical chemistry. B2010
Higher susceptibility to halothane modulation in open- than in closed-channel alpha4beta2 nAChR revealed by molecular dynamics simulations.
Article in The journal of physical chemistry. B, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 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
- Menthol Binding to the Human α4β2 Nicotinic Acetylcholine Receptor Facilitated by Its Strong Partitioning in the Membrane.The journal of physical chemistry. B · 2020Article
- Pentameric Ligand-gated Ion Channels : Insights from Computation.Molecular simulation · 2014Article
- Seeking structural specificity: direct modulation of pentameric ligand-gated ion channels by alcohols and general anesthetics.Pharmacological reviews · 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
- Anesthetic binding in a pentameric ligand-gated ion channel: GLIC.Biophysical journal · 2010Article
- The role of structured water in mediating general anesthetic action on alpha4beta2 nAChR.Physical chemistry chemical physics : PCCP · 2010Article
- Multiple binding sites for the general anesthetic isoflurane identified in the nicotinic acetylcholine receptor transmembrane domain.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- NMR structure of the transmembrane domain of the n-acetylcholine receptor beta2 subunit.Biochimica et biophysica acta · 2010Article
- Unresponsive correlated motion in alpha7 nAChR to halothane binding explains its functional insensitivity to volatile anesthetics.The journal of physical chemistry. B · 2010Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The neuronal alpha4beta2 nicotinic acetylcholine receptor (nAChR) is a potential molecular target for general anesthetics. It is unclear, however, whether anesthetic action produces the same effect on the open and closed channels. Computations parallel to our previous open channel study (J. Phys. Chem. B 2009, 113, 12581) were performed on the closed-channel alpha4beta2 nAChR to investigate the conformation-dependent anesthetic effects on channel structures and dynamics. Flexible ligand docking and over 20 ns molecular dynamics simulations revealed similar halothane-binding sites in the closed and open channels. The sites with relatively high binding affinities (approximately -6.0 kcal/mol) were identified at the interface of extracellular (EC) and transmembrane (TM) domains or at the interface between alpha4 and beta2 subunits. Despite similar sites for halothane binding, the closed-channel conformation showed much less sensitivity than the open channel to the structural and dynamical perturbations from halothane. Compared to the systems without anesthetics, the amount of water inside the pore decreased by 22% in the presence of halothane in the open channel but only by 6% in the closed channel. Comparison of the nonbonded interactions at the EC/TM interfaces suggested that the beta2 subunits were more prone than the alpha4 subunits to halothane binding. In addition, our data support the notion that halothane exerts its effect by disturbing the quaternary structure and dynamics of the channel. The study concludes that sensitivity and global dynamics responsiveness of alpha4beta2 nAChR to halothane are conformation dependent. The effect of halothane on the global dynamics of the open-channel conformation might also account for the action of other inhaled general anesthetics.
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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.