Exploring Quantum Chemical Descriptors and Molecular Docking Approach for Designing Antagonist Search Model for the Glycine/NMDA Receptor Site

Abstract

AbstractAn antagonist selection model, using the combined approach of density functional theory and molecular docking calculations, has been designed for the Glycine site on the NMDA (N‐Methyl‐D‐Aspartate) receptor. The study confirms the presence of an aromatic ring, a mode of delocalization of electron density in the molecule as a requisite for the antagonist activity. The distinguishing nature of agonists vs antagonist molecule at the glycine site can be partly identified by exploring global reactivity descriptors like chemical potential or electrophilicity index. Molecular docking approach used to explore the nature of the active site cavity indicates the presence of an imperforated hydrophobic region in the active site as a requisite for a better binding profile of a potential antagonist molecule. The model developed based on these criteria introduces two new pharmacophoric moieties to be explored for their activity in the Glycine site on the NMDA receptor.