In-silico screening of inhibitor on protein epidermal growth factor receptor (EGFR)
Jeremi Ongko, Jesica Viona Setiawan, Alfina Gracia Feronytha, Agnes Juliana, Andy Effraim, Mariana Wahjudi, Yulanda Antonius
Abstract
Abstract The screening process to detect early-stage lung cancer is injurious to a patient’s survival. Fortunately, there are natural compounds that have been acknowledged to possess anticancer properties, work as the protein binding inhibitors of lung cancer promotors: EGF and EGFR. The study aims to identify inhibitors of EGFR protein binding. Assessments were accomplished based on several parameters related to EGFR proteins, such as pathways, protein activity, conformational changes, and numerous information using the STRING database and KEGG pathway database. Ten inhibitor compounds that expressed highest activity were selected for further analysis were: (20R,22R)-5beta,6beta-Epoxy-4beta,12beta,20-trihy-droxy-1-oxowith-2-en-24-enolide, irinotecan, flavopyridol, teniposide, exatecan, daphnoretin, indirubin, topitecan, wentilactone, and evidiamine. The native ligand Lapatinib was used as positive control in this analysis. The analysis was accomplished by molecular docking using Vina 4 in the PyRx software. Interactions between the ligands and residues were investigated using LIGPLOT+ 2.2. The In-silico analysis of the ten candidate compounds revealed that (20R, 22R)-5beta, 6beta-Epoxy-4beta, 12beta, 20-trihydroxy-1-oxowith-2-en-24-enolide expressed the lowest binding energy value, which is -10.4 kcal/mol, indicated the closest binding energy value to Lapatinib as the control. Based on the interaction of amino acids, (20R,22R)-5beta, 6beta-Epoxy-4beta, 12beta, 20-trihydroxy-1-oxowith-2-en-24-enolide has excellent potential to be utilized as next inhibitor com- pound candidates for EGFR protein, because it binds to the Lys745 residue. It mirrors the positive control and has a binding energy on the range of the specified acceptable parameters.