Data for "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 regulation via allosteric modulators. A recent cryo-EM map of the receptor (EMD 22983) in the presence of (±)-epibatidine revealed the presence of several Coulomb density regions that did not contain an atomic model (PDB ID: 7KOX). We conducted unbiased molecular dynamics simulations of free ligand diffusion of the components of experimental buffers utilized to obtain the cryo-EM structure in the presence of α7-nAChR. In addition to the previously documented binding of epibatidine to the orthosteric site and Ca2+ between E44 and E172, the simulations indicated that epibatidine can also bind within the pore of α7-nAChR. This finding is consistent with the unmodeled Coulomb density observed in the region of the desensitization gate. The data presented here suggests that nAChR ligands characterized as orthosteric binders may bind to additional sites within the receptor and expands the receptor’s pocketome.