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Plant Science Today (PST)

Research Articles

Early Access

Molecular docking and dynamic simulation studies against the ERα of breast cancer using biomolecules from Asparagus aethiopicus L.

DOI
https://doi.org/10.14719/pst.8614
Submitted
1 April 2025
Published
31-10-2025
Versions

Abstract

Globally, breast cancer is the major cause of mortality among women, with a significant proportion of cases associated with estrogen receptor alpha (ERα)-positive subtypes. Targeting ERα has emerged as a promising therapeutic strategy for effective management of breast cancer. This study explores the anticancer potential of bioactive secondary metabolites from the root tubers of Asparagus aethiopicus L. against ERα using a comprehensive in silico approach. Gas Chromatography-Mass Spectrometry (GC-MS) has been utilized to analyze the methanolic extracts of the root tubers. A total of 25 different phytochemicals were screened initially for drug likeness property using Lipinski’s rule of five. Out of eight phytomolecules were selected based on their pharmacokinetic and absorption, distribution, metabolism, excretion and toxicity (ADMET) profiles. Further, six molecules were subjected for molecular docking analysis to assess binding affinity against ERα followed by Molecular Dynamics (MD) simulations, binding free energy (ΔG) calculations, Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) and PCA analysis. Drug-likeness assessments based on Lipinski’s rule identified Pent-3-ene-2-one, 3-phenyl-oxime, Hydroperoxide1-methylbutyl and 4-Hydroxy-2-butanone as promising drug candidates. Molecular docking studies revealed strong interactions with the active site of ERα, whose binding energies vary from -3.8 to -7.3 kcal/mol. These 3 phytomolecules form stable hydrogen bonds with the critical residues of active sides of ERα viz. Glu353, Leu387, Arg394 and Lys449. The structural stability and minimal conformational alterations of ERα with ligand binding was confirmed by MD simulations. The stability of the protein-ligand complexes was supported by Root Mean Square Deviation (RMSD) with minimal deviation in RMSD (<0.6 nm), Root Mean Square Fluctuation (RMSF), Radius of Gyration (Rg) and with Solvent Accessible Surface Area (SASA) which indicates stable protein compactness. Moreover, PCA revealed dominant motions with minimal fluctuation in PC3, suggesting highly stabilized complexes. Hydrogen bond analysis highlighted stable and optimal interaction throughout the simulation. Among the tested compounds, Pent-3-ene-2-one, 3-phenyl-oxime exhibited the lowest binding free energy. This is primarily driven by Vander Waals interactions and polar solvation energy, indicating superior binding affinity. Thus, these finding explains the potential of A. aethiopicus phytochemicals as potent ERα inhibitors and provide a base for future in vitro and in vivo investigation into their application in breast cancer therapy.

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