Molecular simulations of hydrophobic gating of pentameric ligand gated ion channels: Insights into water and ions
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. Mo...
| Автори: | , , , , |
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| Формат: | Journal article |
| Мова: | English |
| Опубліковано: |
American Chemical Society
2021
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| _version_ | 1826257509073027072 |
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| author | Rao, S Klesse, G Lynch, CI Tucker, SJ Sansom, M |
| author_facet | Rao, S Klesse, G Lynch, CI Tucker, SJ Sansom, M |
| author_sort | Rao, S |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T18:19:20Z |
| format | Journal article |
| id | oxford-uuid:05bec3a6-c608-405d-8d0b-702698f2345e |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:19:20Z |
| publishDate | 2021 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | oxford-uuid:05bec3a6-c608-405d-8d0b-702698f2345e2022-03-26T08:58:47ZMolecular simulations of hydrophobic gating of pentameric ligand gated ion channels: Insights into water and ionsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:05bec3a6-c608-405d-8d0b-702698f2345eEnglishSymplectic ElementsAmerican Chemical Society2021Rao, SKlesse, GLynch, CITucker, SJSansom, MIon 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. |
| spellingShingle | Rao, S Klesse, G Lynch, CI Tucker, SJ Sansom, M Molecular simulations of hydrophobic gating of pentameric ligand gated ion channels: Insights into water and ions |
| title | Molecular simulations of hydrophobic gating of pentameric ligand gated ion channels: Insights into water and ions |
| title_full | Molecular simulations of hydrophobic gating of pentameric ligand gated ion channels: Insights into water and ions |
| title_fullStr | Molecular simulations of hydrophobic gating of pentameric ligand gated ion channels: Insights into water and ions |
| title_full_unstemmed | Molecular simulations of hydrophobic gating of pentameric ligand gated ion channels: Insights into water and ions |
| title_short | Molecular simulations of hydrophobic gating of pentameric ligand gated ion channels: Insights into water and ions |
| title_sort | molecular simulations of hydrophobic gating of pentameric ligand gated ion channels insights into water and ions |
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