Based on published affinity-labeling and mutagenesis experiments describing the effect of changes in specific amino acids in molecular biological studies on the nicotinic acetylcholinergic receptor (nAChR), we have identified 12 amino acids which are important in functioning at the nicotinic cholinergic receptor. The work presented here provides an atomistic model of this important receptor based on our molecular modeling studies. We found five of these amino acids (TRP86, ASP89, TYR93, ASP138, and THR191) to be associated with the cationic end of acetylcholine (ACh), which is electron-deficient. Three other amino acids (ARG209, TYR190, and TYR198) are associated with the ester end, where an enhanced electron density is present. After hydrogen bonding between the two oxygen atoms at the ester end, and two of the guanidinium hydrogen atoms in ARG209. ASP200 hydrogen bonds to the other two hydrogen atoms of the guanidinium group, thus forming a pseudo-ring. Two aromatic amino acids (TRP149 and TYR151) then enhance the binding at the pseudo-ring through additional hydrogen bonding and charge-transfer complexation, with THR150 functioning to further stabilize this evolving charge-transfer complex. We postulate that this latter process allows the ion channel to twist, thus opening it. From the published amino acid sequence in the polypeptides at the 5HT-3, GABA, and glycine receptors (Maricq et al.: Science 254:432-437, 1991), we also speculate on which amino acids are involved in these three receptors.