مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Molecular docking study of resveratrol as LSD1 inhibitor in glioblastoma multiforme
Molecular docking study of resveratrol as LSD1 inhibitor in glioblastoma multiforme
Tooba Abdizadeh,1,*
1. Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
Introduction: Background: Glioblastoma multiforme (GBM) is one of the most aggressive malignancies of central nervous system tumors, with a median overall survival of approximately 15 months, and it remains largely incurable. Lysine-specific demethylase 1 (LSD1), a flavin-containing oxidoreductase, is a key histone-modifying enzyme belonging to the histone demethylase (KDM) subfamily and is responsible for master regulation of several signaling pathways in glioma cells. This study explored the therapeutic effect of resveratrol as an LSD1 inhibitor on glioblastoma multiforme by the molecular docking method.
Methods: The 3D structure of resveratrol was obtained from PubChem (CID: 445154), and the crystal structure of LSD1 was retrieved from the RCSB site (PDB: 5L3E). Using UCSF Chimera and Autodock software, applied the desired changes (such as removing extra molecules, adding hydrogen, adding charge, converting protein and ligands to Pdbqt) on the protein and ligands. The molecular docking on the protein and ligand was done, and the obtained results were analyzed using the Discovery Studio.
Results: The binding free energy of the resveratrol in the best conformation in the binding pocket of the protein was -5.10. The resveratrol forms two hydrogen bonds with amino acid residues of Asn540 and The335, and an H-arene with His812 in the interaction with the receptor.
Conclusion: The findings of this study showed that the bonding of resveratrol to the LSD1 protein resulted in the reduction of the protein activity. Consequently, resveratrol can be further investigated as a chemotherapeutic agent for the treatment of glioblastoma multiforme.