Molecular Docking of Silymarin as a Ligand for Aromatase Enzyme and HIV-1 Reverse Transcriptase Using Molegro Virtual Docker

Abstract

Background: Molegro Virtual Docker (MVD) software is specifically designed for executing the molecular docking process. It has gained recognition among docking software for its user-friendliness, affordability, and quick result evaluation. The docking procedure can utilize multiple algorithms, and different molecules can be treated as ligands and receptors. Selin marine is one compound that, owing to its appropriate structure, can significantly function as a ligand and inhibitor for key enzymes involved in pathogenesis. Objectives: The primary objective of this research is to perform in silico analyses to explore the potential of silibinin, silidianin, and silychristin molecules as ligands for interaction with the active sites of the Aromatase enzyme and human immunodeficiency virus-1 (HIV-1) reverse transcriptase enzymes. Methods: In this research, the ligand structures were initially obtained from the PubChem database, while the enzyme structures were sourced from the PDB database. Subsequently, the docking process was conducted using the MVD software. Any structural errors in the molecules were rectified utilizing the 'if missing' approach. The cavities associated with the active sites of each enzyme were identified based on the positioning of the primary ligand. To ensure the docking process was executed with maximum precision, the MolDock Score (GRID) and the MolDock simplex evolution (SE) algorithm were employed in the settings, with ten runs conducted for each molecule. Results: The findings from the docking process revealed that the molecules silibinin, silidianin, and silychristin can occupy the active site of the aromatase enzyme, exhibiting free energies of -141.972, -127.805, and -148.425 kcal/mol, respectively. Their ability to form steric interactions and hydrogen bonds suggests that they could serve as effective ligands for interaction with this active site. Furthermore, these ligands exhibit significant potential for establishing hydrogen and ester bonds within the active site of HIV-1 reverse transcriptase, with calculated free energies of -140.701, -138.956, and -135.365 kcal/mol for silibinin, silidianin, and silychristin, respectively. Conclusions: Silymarin demonstrated the ability to interact with the active site of the aromatase enzyme and HIV-1 reverse transcriptase, potentially competing with their primary ligands for binding at this location, thereby inhibiting the activity of both enzymes in affected cells.