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Updated: May 31, 2026
Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
Published on: May 20, 2020
In silico screening of epidermal growth factor receptor (EGFR) in the tyrosine kinase domain through a medicinal
Orathai Sawatdichaikul1, Supa Hannongbua, Chak Sangma
1Department of Biochemistry, Kasetsart University, Bangkok, Thailand.
Abstract:
The unregulated epidermal growth factor receptor tyrosine kinase (ErbB1-TK or EGFR-TK) protein is involved in the proliferation of more than 50% of all cancer types. The reduction of EGFR-TK activity by small or medium-sized molecules has been proven to be an effective treatment for cancer. There is a widespread belief that Chinese medicinal herbs are active against several diseases, including various types of cancer. In this study, 29,960 compounds from the Chemiebase medicinal compound database were virtually screened against the EGFR-TK using AutoDock4.0, GOLD and GLIDE (XP). The results revealed eight potential hits: CAS nos. 104096-45-9, 112649-21-5, 113866-89-0, 142608-98-8, 142608-99-9, 144761-33-1, 155233-17-3 and 80510-05-0. These compounds have been reported to show anticancer activities in the literature. With the help of SiMMap and MOE interaction analysis, the protein-ligand interaction patterns between the functional groups of these compounds and the binding pocket residues were analyzed. Hydrogen bonding and hydrophobic forces are the main components of the interactions of these hits, similar to those observed for the known inhibitors erlotinib, gefitinib and AEE. The physicochemical filter indicates that compounds CAS nos. 104096-45-9 and 144761-33-1 are likely to be potential leads in the drug discovery process.
Insights
This study screened 29,960 compounds for activity against epidermal growth factor receptor tyrosine kinase (EGFR-TK), a key driver in many cancers. Eight potential anticancer compounds were identified, with two showing promise for drug discovery.
Area of Science:
- Computational chemistry
- Drug discovery
- Oncology
Background:
- Unregulated epidermal growth factor receptor tyrosine kinase (EGFR-TK) drives proliferation in over 50% of human cancers.
- Targeting EGFR-TK with small molecules is an effective cancer treatment strategy.
- Traditional Chinese medicinal herbs are increasingly recognized for their potential therapeutic properties.
Purpose of the Study:
- To virtually screen a large library of Chinese medicinal compounds for potential EGFR-TK inhibitors.
- To identify novel compounds with anticancer activity against EGFR-TK.
- To analyze the binding interactions of identified compounds with EGFR-TK.
Main Methods:
- Virtual screening of 29,960 compounds from the Chemiebase database against EGFR-TK using AutoDock4.0, GOLD, and GLIDE (XP).
- Protein-ligand interaction analysis using SiMMap and MOE.
- Physicochemical filtering to assess drug-likeness.
Main Results:
- Eight compounds (CAS nos. 104096-45-9, 112649-21-5, 113866-89-0, 142608-98-8, 142608-99-9, 144761-33-1, 155233-17-3, 80510-05-0) were identified as potential EGFR-TK inhibitors.
- Interaction analysis revealed hydrogen bonding and hydrophobic forces as key binding mechanisms, similar to known inhibitors.
- Compounds CAS nos. 104096-45-9 and 144761-33-1 passed physicochemical filters, indicating potential as drug leads.
Conclusions:
- Virtual screening successfully identified promising natural compounds targeting EGFR-TK.
- The identified compounds exhibit binding modes comparable to existing EGFR-TK inhibitors.
- Compounds CAS nos. 104096-45-9 and 144761-33-1 warrant further investigation as potential anticancer drug candidates.
