Stroke is a disease that has yet to be effectively prevented. It is now known that excitotoxins released by N-Methyl-D-aspartate receptor（NMDAR）are the primary cause of stroke. Breakthroughs in stroke related research indicate that NMDAR subtypes have different neural functions: NR2A is associated with neural protection whereas NR2B is associated with inducing neural death. This research utilized the comprehensive traditional Chinese medicine Database@Taiwan to identify potent natural traditional Chinese medicine (TCM) compounds that can simultaneously promote NR2A and inhibit NR2B. Virtual screening against NMDAR indicated that Dencicihine、Alliin formed highly similar interactions with the controls in NR2A and NR2B. Molecular dynamics simulations results further supported docking results. Dencicihine、Alliin formed high occupancy H-bonds in addition to cation interactions and salt bridges, which contributed to higher stability within NR2A and NR2B. Our results indicate that TCM compounds Dencicihine、Alliin may bind with NR2A and NR2B simultaneously. The dual binding characteristics may be helpful for the development of dual targeting drugs, and through simplifying therapy, may reduce the risk of adverse side-effects.
