What question did this study set out to answer?

To investigate the binding of epibatidine at the α7-nicotinic acetylcholine receptor's desensitization gate using molecular dynamics and cryo-EM.

February 11, 20260 citationsOpen Access

Evidence for Epibatidine Binding to the Desensitization Gate in α7 nAChR from Molecular Dynamics Simulations and Cryo-EM

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JKJesko Kaiser CGChristoph G. W. Gertzen DMDaniel Mann

Key Points

To investigate the binding of epibatidine at the α7-nicotinic acetylcholine receptor's desensitization gate using molecular dynamics and cryo-EM.
Conducted unbiased molecular dynamics simulations of buffer components around α7-nAChR.
Utilized cryo-EM structure (EMD 22983; PDB ID 7KOX) to analyze binding sites.
Examined Coulomb density to identify potential binding locations.
Epibatidine can occupy both the orthosteric site and the pore near the desensitization gate.
Findings are consistent with unmodeled Coulomb density in the cryo-EM structure.
Expands understanding of the receptor's binding pocket and allosteric modulation.

Abstract

The homopentameric α7-nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel widely expressed in the human nervous system and susceptible to allosteric modulation. A recent cryo-EM structure (EMD 22983; PDB ID 7KOX) revealed unassigned Coulomb density. Unbiased molecular dynamics simulations of buffer components around α7-nAChR show that (±)-epibatidine can occupy not only the orthosteric site but also the pore near the desensitization gate, consistent with the unmodeled Coulomb density and expanding the receptor’s pocketome.

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Cite This Study

Kaiser et al. (2026) studied this question.

synapsesocial.com/papers/698c1c73267fb587c655eebd https://doi.org/10.34734/fzj-2026-01275

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February 11, 20260 citationsOpen Access

Evidence for Epibatidine Binding to the Desensitization Gate in α7 nAChR from Molecular Dynamics Simulations and Cryo-EM

View Full Paper

JKJesko Kaiser CGChristoph G. W. Gertzen DMDaniel Mann

Key Points

To investigate the binding of epibatidine at the α7-nicotinic acetylcholine receptor's desensitization gate using molecular dynamics and cryo-EM.
Conducted unbiased molecular dynamics simulations of buffer components around α7-nAChR.
Utilized cryo-EM structure (EMD 22983; PDB ID 7KOX) to analyze binding sites.
Examined Coulomb density to identify potential binding locations.
Epibatidine can occupy both the orthosteric site and the pore near the desensitization gate.
Findings are consistent with unmodeled Coulomb density in the cryo-EM structure.
Expands understanding of the receptor's binding pocket and allosteric modulation.

Abstract

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Cite This Study

Kaiser et al. (2026) studied this question.

synapsesocial.com/papers/698c1c73267fb587c655eebd https://doi.org/10.34734/fzj-2026-01275

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