Garrett D Santis, Yuika Okura, Keisuke Hirata, Shun-Ichi Ishiuchi, Masaaki Fujii, Sotiris S Xantheas
The binding affinity of nicotinoids to the binding residues of the α4 β2 variant of the nicotinic acetylcholine receptor (nAChR) was identified as a strong predictor of the nicotinoid's addictive character. Using ab initio calculations for model binding pockets of increasing size composed of 3, 6, and 14 amino acids (3AA, 6AA, and 14AA) that are derived from the crystal structure, the differences in binding affinity of 6 nicotinoids, namely, nicotine (NIC), nornicotine (NOR), anabasine (ANB), anatabine (ANT), myosmine (MYO), and cotinine (COT) were correlated to their previously reported doses required for increases in intracranial self-stimulation (ICSS) thresholds, a metric for their addictive function...
May 2, 2024: Journal of Physical Chemistry. B