Ethnomedicine claim directed in-silico prediction of epidermal growth factor receptor kinase antagonist: an untapped reservoir of prospective anticancer agents

Abstract

The epidermal growth factor receptor (EGFR) is a tyrosine kinase (TK) that belongs to the ErbB family and governs important cellular functions like reproduction, survival, motility, and differentiation. Overexpression, intensification, and alteration of EGFR occur in a wide range of human malignancies and are associated with tumor progression and decreased anticancer drug sensitivity. As a result, EGFR has been identified as one of the primary anticancer targets. As cancer is more likely to be poorly understood in traditional medical practices, the extrapolation of an ethnomedicine-led strategy to identifying and prioritizing anticancer medicinal plants has been questioned. Nonetheless, given the challenges of developing innovative anticancer drugs that are effective, safe, inexpensive, and widely available, ethnomedicinal studies play critical roles in identifying relevant medicinal plants that can be further investigated. This study employed pharmacophore modeling, molecular docking, and molecular dynamics simulation to develop an effective agent as an inhibitor for EGFR. The final findings revealed that the selected bioactive compound stabilized the EGFR protein. The optimum orientations of the various inhibitors was Friedelin and it was chosen and subjected, along with the FDA-approved drug, to molecular dynamics modeling to determine the molecular interaction of the medication with various mutational sites in order to deduce the suitable orientation for the inhibitors. The study also attest to the ethnomedicinal claims that ethnomedicinal plants played a huge role in anticancer drug discovery and that their exploration can change the bleak picture cancer paints in our societies today.

Computational Exploration of Berberis lycium Royle: A Hidden Treasure Trove for Antiviral Development

“… 83 In addition, other factors such as temperature, solvent conditions, and simulation parameters can also influence Rg values and protein stability. 78 These results provide insights into the structural dynamics of the protein targets in a complex with berberine and highlight the potential impact of ligand binding on protein stability and flexibility.…”

“…Previous studies have shown that the RMSD of a ligand can be affected by the conformational changes of the protein side chains that form hydrogen bonds or van der Waals interactions with the ligand. 78 , 79 Therefore, differences in the binding interactions of different protein target with berberine may also contribute to the differences in their RMSD values. In summary, the RMSD plot of the MD simulation provides valuable information about the stability and conformational changes of the protein-ligand complex.…”

Cracking the Code of Antibiotic Resistance OF Klebsiella pneumoniae ST16: A Computational Exploration of Whole Genome Sequences for Beta-lactam Resistance and the Discovery of NMD-1 Resistance Gene Inhibitor

“…To identify a potential medication that could inhibit the function of epidermal growth factor receptor kinase, protein-ligand docking studies were conducted using Autodock Vina and PyRx 8.0. [17] The grid map for docking calculations was centered on the target proteins, and BIOVIA Discovery Studio version 21.1 was utilized to simulate non-bonded polar and hydrophobic interactions at the inhibitor site of 3RKJ. Standard docking protocols were employed for subsequent docking procedures.…”