Mujahid M Almuqati^1*, Rayan A Alghamdi¹ and Isam M Abu Zeid^1,2,3

¹Department of Biological Sciences, Faculty of Science, King Abdulaziz University,
Jeddah, Saudi Arabia
²Centre of Excellence in Bionanoscience, King Abdulaziz University, Jeddah, Saudi
Arabia
³Princess Dr. Najla Bint Saud Al-Saud Center for Excellence Research in
Biotechnology, King Abdulaziz University, Jeddah, Saudi Arabia

*Corresponding Author: Mujahid M Almuqati, Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.

Received: April 07, 2026; Published: May 07, 2026

Objective: Epidermal growth factor receptor (EGFR) is a clinically validated therapeutic target in non-small cell lung cancer (NSCLC), and plant-derived phytochemicals may provide diverse lead scaffolds; thus, this study aimed to evaluate six bioactive compounds from Opuntia ficus-indica as potential EGFR kinase inhibitors in silico.

Methods: Compounds were docked into the EGFR kinase domain (PDB ID: 1XKK) using molecular docking, and the top-ranked ligands were further assessed by 100-ns molecular dynamics (MD) simulations and MM-PBSA binding free-energy calculations; the docking protocol was validated by redocking the co-crystallized ligand and computing RMSD.

Results: Docking indicated favorable accommodation within the ATP-binding pocket, with nicotiflorin (−9.43 kcal/mol), rutin (−9.11 kcal/mol), and quercetin (−8.91 kcal/mol) selected for MD/MM-PBSA, showing interactions with key ATP-site residues (e.g., Met793 and Lys745) and additional contacts including Cys797 (nicotiflorin/rutin) and Asp855 (quercetin); redocking achieved a heavy-atom RMSD of 1.268 Å, MD trajectories showed stable backbone behavior (RMSD ~0.14–0.31 nm) and maintained compactness (Rg ~1.93–2.04 nm), hydrogen-bond persistence was highest for rutin (average ~7.13; max 12) versus nicotiflorin (~4.55; max 9) and quercetin (~2.30; max 5), and MM-PBSA estimated ΔTOTAL values of −36.70 ± 5.52 (rutin), −25.58 ± 5.07 (nicotiflorin), and −23.17 ± 3.18 kcal/mol (quercetin), with favorable van der Waals/electrostatics partially offset by polar solvation and stabilized by non-polar solvation.

Conclusion: The combined docking–MD–MM-PBSA findings nominate rutin, nicotiflorin, and quercetin as the most promising Opuntia ficus-indica –derived EGFR-binding candidates in silico and support subsequent experimental validation in enzymatic and cell-based EGFR assays.

Keywords: Non-Small Cell Lung Cancer; Opuntia ficus-indica; Molecular Docking; Molecular Dynamics Simulation

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Citation

Citation: Mujahid M Almuqati., et al. “In Silico Identification of Opuntia ficus-indica Phytochemicals as Potential EGFR Kinase Inhibitors in Non–Small Cell Lung Cancer: Molecular Docking, Molecular Dynamics Simulation, and MM-PBSA Analyses". Acta Scientific Medical Sciences 10.5 (2026): 31-41.

Copyright

Copyright: © 2026 Mujahid M Almuqati., et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.