@article {2017|2096,
	title = {String method solution of the gating pathways for a pentameric ligand-gated ion channel.},
	journal = {Proc Natl Acad Sci U S A},
	volume = {114},
	year = {2017},
	month = {2017 05 23},
	pages = {E4158-E4167},
	abstract = {<p>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.</p>
},
	keywords = {Computer Simulation, Ligand-Gated Ion Channels, Models, Biological, Models, Chemical},
	issn = {1091-6490},
	doi = {10.1073/pnas.1617567114},
	author = {Lev, Bogdan and Murail, Samuel and Poitevin, Fr{\'e}d{\'e}ric and Cromer, Brett A and Marc Baaden and Delarue, Marc and Allen, Toby W}
}
@article {2014|1792,
	title = {Allosteric regulation of pentameric ligand-gated ion channels: An emerging mechanistic perspective},
	journal = {Channels},
	volume = {8},
	number = {4},
	year = {2014},
	pages = {350{\textendash}360},
	keywords = {Allosteric Regulation, Animals, chemistry/metabolism, Humans, Ion Channel Gating, Ligand-Gated Ion Channels, metabolism, Models, Molecular, Protein Multimerization, Small Molecule Libraries},
	author = {Antoine Taly and J{\'e}r{\^o}me H{\'e}nin and Changeux, Jean-Pierre and Cecchini, Marco}
}
