Work

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

Year: 2026

Type: article

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.

Source: Journal of Chemical Information and Modeling

DOI: 10.1021/acs.jcim.5c02384

Authors: Jesko Kaiser, Christoph G. W. Gertzen, Daniel Mann, Carsten Sachse, Holger Gohlke

Institutions: Heinrich Heine University Düsseldorf, Forschungszentrum Jülich, Ernst Ruska Centre

Language: English

Topic: Nicotinic Acetylcholine Receptors Study

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funder: Deutsche Forschungsgemeinschaft

Award: Zentrum für strukturelle Studien