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Updated: Oct 13, 2025

Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
Published on: May 20, 2020
Icotinib, Almonertinib, and Olmutinib: A 2D Similarity/Docking-Based Study to Predict the Potential Binding Modes and
Faisal A Almalki1, Ahmed M Shawky2,3, Ashraf N Abdalla4,5
1Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Umm Al-Qura University, Makkah 21955, Saudi Arabia.
Abstract:
In the current study, a 2D similarity/docking-based study was used to predict the potential binding modes of icotinib, almonertinib, and olmutinib into EGFR. The similarity search of icotinib, almonertinib, and olmutinib against a database of 154 EGFR ligands revealed the highest similarity scores with erlotinib (0.9333), osimertinib (0.9487), and WZ4003 (0.8421), respectively. In addition, the results of the docking study of the three drugs into EGFR revealed high binding free energies (ΔG = -6.32 to -8.42 kcal/mol) compared to the co-crystallized ligands (ΔG = -7.03 to -8.07 kcal/mol). Analysis of the top-scoring poses of the three drugs was done to identify their potential binding modes. The distances between Cys797 in EGFR and the Michael acceptor sites in almonertinib and olmutinib were determined. In conclusion, the results could provide insights into the potential binding characteristics of the three drugs into EGFR which could help in the design of new more potent analogs.
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