ArticleProceedings of the National Academy of Sciences of the United States of America2017
String method solution of the gating pathways for a pentameric ligand-gated ion channel.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 79 citations in OpenAlex.
- Article
- General anesthetic modulation of a pentameric ligand-gated ion channel explored with simulations.Biophysical journal · 2026Article
- Data-driven enhanced sampling of mechanistic pathways.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Asymmetric gating of a homopentameric ion channel GLIC revealed by cryo-EM.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- A Pore-Facing Glycan Determines GABAA Receptor Subunit Stoichiometry and Gating Behavior.Research square · 2025Article
- Polymorphism in Glu-Phe-Asp Proteinoids.Biomimetics (Basel, Switzerland) · 2025Article
- Resolving the conformational ensemble of a membrane protein by integrating small-angle scattering with AlphaFold.PLoS computational biology · 2025Article
- Adaptive sampling-based structural prediction reveals opening of a GABAScience advances · 2025Article
- Electrically silent mutants unravel the mechanism of binding-gating coupling in Cys-loop receptors.Science advances · 2024Article
- Atomistic mechanisms of the regulation of small-conductance CaProceedings of the National Academy of Sciences of the United States of America · 2024Article
- MinActionPath2: path generation between different conformations of large macromolecular assemblies by action minimization.Nucleic acids research · 2024Article
- Cryo-EM structures of prokaryotic ligand-gated ion channel GLIC provide insights into gating in a lipid environment.Nature communications · 2024Article
- A weak coupling mechanism for the early steps of the recovery stroke of myosin VI: A free energy simulation and string method analysis.PLoS computational biology · 2024Article
- A release of local subunit conformational heterogeneity underlies gating in a muscle nicotinic acetylcholine receptor.Nature communications · 2024Article
- Facilitation of hERG Activation by Its Blocker: A Mechanism to Reduce Drug-Induced Proarrhythmic Risk.International journal of molecular sciences · 2023Review
- Conformational transitions and allosteric modulation in a heteromeric glycine receptor.Nature communications · 2023Article
- Personalized structural biology reveals the molecular mechanisms underlying heterogeneous epileptic phenotypes caused byHGG advances · 2022Article
- Structural and dynamic mechanisms of GABANature communications · 2022Article
- A Companion Guide to the String Method with Swarms of Trajectories: Characterization, Performance, and Pitfalls.Journal of chemical theory and computation · 2022Article
- Computational methods and theory for ion channel research.Advances in physics: X · 2022Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Pentameric ligand-gated ion channels control synaptic neurotransmission by converting chemical signals into electrical signals. Agonist binding leads to rapid signal transduction via an allosteric mechanism, where global protein conformational changes open a pore across the nerve cell membrane. We use all-atom molecular dynamics with a swarm-based string method to solve for the minimum free-energy gating pathways of the proton-activated bacterial GLIC channel. We describe stable wetted/open and dewetted/closed states, and uncover conformational changes in the agonist-binding extracellular domain, ion-conducting transmembrane domain, and gating interface that control communication between these domains. Transition analysis is used to compute free-energy surfaces that suggest allosteric pathways; stabilization with pH; and intermediates, including states that facilitate channel closing in the presence of an agonist. We describe a switching mechanism that senses proton binding by marked reorganization of subunit interface, altering the packing of β-sheets to induce changes that lead to asynchronous pore-lining M2 helix movements. These results provide molecular details of GLIC gating and insight into the allosteric mechanisms for the superfamily of pentameric ligand-gated channels.
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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.