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

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