Molecular docking and MD simulation approach to identify potential phytochemical lead molecule against triple negative breast cancer - Supplementary Table.docx

AbstractBackground: Triple-negative breast cancers are defined as tumors that lack expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). It exhibits unique clinical and pathologic features, is highly aggressive and has relatively poor prognosis and poor clinical outcome.Objective: Identify a novel drug target protein against Triple-negative breast cancer (TNBC) and also identify potential phytochemical lead molecule against the novel drug target.Methods: In the study, we retrieved TNBC samples from NGS and microarray datasets from GEO database and employed a combination of differential gene expression studies, protein-protein interaction analysis and network topology investigation to identify the target protein. Using molecular docking and molecular dynamics simulation studies followed by MM-GBSA the potential lead molecule was identified.Result: Androgen receptor (AR) was found to be the target protein and 2-hydroxynaringenin was discovered to be a possible phytochemical lead molecule to combat TNBC.Upregulated genes with LogFC > 1.25 and P-value < 0.05 from TNBC gene expression dataset were given to STRING tool to investigate the network toplology and Androgen receptor (AR) was found to be an appropriate hub gene in the protein-protein interaction network. Phytochemicals that inhibit breast cancer were retrieved from PubChem database and virtual screening was done using PyRx against the AR protein. Based on Lipinski's rule and ADMET properties, molecular interaction studies were analysed by induced fit docking, wherein significant binding interaction was displayed by 2-hydroxynaringenin. Molecular dynamics studies and MM-GBSA of AR and 2-hydroxynaringenin complex exhibited strong and stable interactions.