New Insights on N-Methyl-D-Aspartate (NMDA) Receptor Under Combinatorial Molecular Docking and MD Simulation Studies Using Natural Bioactive Compounds Against Neurodegenerative Diseases

Neurodegenerative diseases pose a significant challenge, and novel therapeutic strategies are urgently needed. N-methyl-D-aspartate (NMDA) receptor is reported to play a critical role in the central nervous system and has emerged as a potential target for drug discovery. This study explored the potential scope of natural bioactive compounds as ligands for the NMDA receptor using current advances of docking studies with molecular dynamic (MD) simulations. An extensive virtual screening of 500 natural compounds were executed based on wide scientific literature and bibliography search. Docking simulations identified promising candidates with favorable binding affinities, with the top compounds - DL-Alanosine, and Zeinoxanthin (PubChem CIDs 153353 and 5281234) exhibiting exceptionally high docking scores of -6.6 and -6.4, against NMDA respectively. Further, MD simulations suggested the stability of the top-scoring compounds in complex with the NMDA receptor. These findings will provide a new insights to researchers and scientists on proceeding with new alternatives on the investigation of natural bioactive compounds as therapeutic lead candidates for targeting various receptors like NMDA in neurodegenerative diseases. However, in vitro and in vivo studies are warranted to validate these results and elucidate the underlying mechanisms of action.