Ligand-Based Drug Discovery for Insomnia: Re...

Ligand-Based Drug Discovery for Insomnia: Repurposing Zolpidem Analogues Using Morgan Fingerprints

Author Name : Samruddhi Vinod Kandele, Shonak Sandeep Adivarekar, Babaso Vithal Udugade

DOI: https://doi.org/10.56025/IJARESM.2024.1211241785

ABSTRACT This study identifies Zolpidem as a promising lead ligand for developing new therapeutic agents targeting insomnia. Zolpidem’s selective binding to the GABAA receptor α1 subunit, coupled with its clinical efficacy, rapid onset, and short duration of action, underscores its potential in acute insomnia treatment with a low dependency risk. Ligand screening and molecular docking using the DrugRep platform revealed Zolpidem’s strong binding affinity, with a docking score of -8.7 in the C5 binding pocket and favorable interactions with residues such as Y250, T256, L259, and L264. These interactions enhance GABAergic activity and stabilize the receptor-ligand complex, thereby improving sleep induction. Structural validation using the Ramachandran plot confirmed the reliability of the protein model, with 87.5% of residues in favored regions, supporting the docking results.