Identification of Gly/NMDAR Antagonist from Chromolaena odoratas Derived Phytoconstituents using Induced Fit Docking Approach.

The ionotropic activation of N-methyl-D-aspartic acid (NMDA) plays a significant role in different type of neurodegenerative disease, as it is a tetramer with two Glycine binding subunit and two glutamate subunits. NMDA receptor can be inhibited by either blocking of the glycine site or glutamate site. Previously reported inhibitors of NMDA receptor focus on the inhibition of the glutamate subunit, which was reported to be associated with side effects such as ataxia, memory deficits, neurotoxicity. Therefore, different compounds with antagonistic effect are been explored on Gly/NMDA site. Glide XP docking was employed in screening phyto-constituent of Chromolaena odorata against Gly/NMDA receptor for hit compounds with antagonistic properties. The hit compounds were further subjected to Induced fit docking (IFD) and lipinski rule of five. The final selection was based on Rigid XP docking score using co-crystallized ligand as threshold docking score, interaction with receptor site residues, and IFD score. Ferulic acid, caffeic acid and scutellarein recorded binding affinity of -8.752Kcal/mol, 10.004 Kcal/mol and - 9.096 Kcal/mol respectively, which is higher than the binding affinity of co-crystallized ligand. Induced fit score obtained were -614.38, -614.03 and -616.31 for ferulic acid, caffeic acid and scutellarein respectively. The Adme properties of the phyto-constituent indicated that the compounds are drug-like in nature.