The Docking and Dynamics Simulation of Natural Compounds from Abrus precatorius L. for Investigating the Possibility of GluR3 Inhibition to Treat Depression

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Background The rising incidence of Major Depressive Disorder (MDD), in conjunction with the inadequate effectiveness and resistance observed in existing therapeutic approaches, emphasizes the urgent need to investigate novel therapeutics that provide enhanced efficacy with reduced adverse effects. Abrus precatorius L., an herb that is readily available and frequently utilized in traditional medicine, is frequently prescribed to patients suffering from neurological disorders. Objectives The goal of this study is to discover novel active compounds from the A. precatorius plant that can specifically target the GluR3 receptor using in silico techniques, to develop a safe and efficient treatment for MDD. Materials and Methods Homology modeling, molecular docking, molecular dynamics simulation, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis were employed in this investigation to screen compounds derived from A. precatorius . Their potential to inhibit α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor activity, specifically glutamate receptor 3 (GluR3), which is associated with MDD, was the objective of this study. Results Among 31 compounds derived from A. precatorius , 15 successfully cleared the ADMET filter criteria. Subsequently, the best homology model of GluR3 was constructed using Phyre2. This facilitated an investigation into the intramolecular interactions exhibited by the filtered compounds. Notably, the four compounds with the most pronounced binding affinities are identified by their PubChem compound IDs (CIDs): 160511, 44257585, 1983, and 145857. The binding affinity and internal molecular interactions of the top-ranking compound, PubChem CID 160511, were subjected to further validation through MD simulations, affirming its sustained stability in binding. Conclusion CIDs: The compound 160511 cleared ADMET analysis with no notable side effects and high binding affinity and stability, making it a potential drug candidate for MDD. To ascertain the precise efficacy of medications, additional in vitro, in vivo , and clinical studies are required.

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