24 August 2019
The α7 nicotinic acetylcholine receptors (nAChRs) are widely expressed in the central and peripheral nervous systems and are important drug targets for the treatment of neurological diseases. However, differentiation of the agonists and antagonists of the nAChR is difficult. In this study we aimed to develop a reliable and efficient computational approach for differentiation of the agonists from the antagonists of the nAChR based on a systematical analysis of 123 ligands (87 agonists, 12 partial agonists, and 24 antagonists) binding with the extracellular domain of the α7 nAChR chimera. Our results suggest that the ligand size and ligand binding affinity cannot differentiate the agonists from the antagonists of the nAChR. The ligand efficiency that considers both ligand binding affinity and size for the agonists is overall more left shifted in comparison to the antagonists, but the values of the ligand efficiency still cannot differentiate the agonists from the antagonists unless the values are either relatively high (more than −0.3 kcal mol −1) or relatively low (less than −0.45 kcal mol −1). Our results suggest that accurate prediction of the agonist or antagonist of the nAChR is challenging and the ligand innate configuration has to be considered as an extra for differentiation of the agonists from the antagonists of the nAChR.