Evidence for Epibatidine Binding to the Desensitization Gate in α7 nAChR from Molecular Dynamics Simulations and Cryo-EM
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.
Fields of Study & Subjects
Nicotinic Acetylcholine Receptors Study
Ion channel regulation and function
Receptor Mechanisms and Signaling
Publication details
- Journal / source
- Journal of Chemical Information and Modeling
- Publisher
- American Chemical Society (ACS)
- Volume
- 66
- Issue
- 3
- Pages
- 1337–1341
- Publication date
- 27 January 2026
- Language
- EN