Molecular Simulations of Hydrophobic Gating of Pentameric Ligand Gated Ion Channels: Insights into Water and Ions
| Autor: | Charlotte I. Lynch, Gianni Klesse, Stephen J. Tucker, Shanlin Rao, Mark S.P. Sansom |
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| Rok vydání: | 2021 |
| Předmět: |
010304 chemical physics
Chemistry Biological membrane Gating 010402 general chemistry 01 natural sciences 0104 chemical sciences Surfaces Coatings and Films Ion Nanopore Chemical physics Polarizability Perspective 0103 physical sciences Materials Chemistry Ligand-gated ion channel Dewetting Physical and Theoretical Chemistry Ion channel |
| Zdroj: | The Journal of Physical Chemistry. B |
| ISSN: | 1520-5207 1520-6106 |
| DOI: | 10.1021/acs.jpcb.0c09285 |
| Popis: | Ion channels are proteins which form gated nanopores in biological membranes. Many channels exhibit hydrophobic gating, whereby functional closure of a pore occurs by local dewetting. The pentameric ligand gated ion channels (pLGICs) provide a biologically important example of hydrophobic gating. Molecular simulation studies comparing additive vs polarizable models indicate predictions of hydrophobic gating are robust to the model employed. However, polarizable models suggest favorable interactions of hydrophobic pore-lining regions with chloride ions, of relevance to both synthetic carriers and channel proteins. Electrowetting of a closed pLGIC hydrophobic gate requires too high a voltage to occur physiologically but may inform designs for switchable nanopores. Global analysis of ∼200 channels yields a simple heuristic for structure-based prediction of (closed) hydrophobic gates. Simulation-based analysis is shown to provide an aid to interpretation of functional states of new channel structures. These studies indicate the importance of understanding the behavior of water and ions within the nanoconfined environment presented by ion channels. |
| Databáze: | OpenAIRE |
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