Comprehensive In Silico Analysis of Flavonoids in Breast Cancer Using Molecular Docking, <scp>ADME</scp>, and Molecular Dynamics Simulation Approach

ABSTRACT The most frequent type of breast cancer in women is infiltrating ductal carcinoma, followed by infiltrating lobular carcinoma and triple‐negative breast cancer, which account for 10%–15% of cases. Since this disease is not aggressive in its early stages and thus does not flee with the breast duct with this perspective, Epidermal Growth Factor Receptor (EGFR) was chosen with its relevance in stage 0 breast cancer as a primary target. The study aimed to evaluate the protective effects of 19 flavonoids against breast cancer. In addition, pharmacokinetics investigations, molecular docking, free energy calculations, and molecular dynamics simulations were used to evaluate the molecular interactions, stability, and draggability between the phytoconstituents and the EGFR. The acquired results showed that myricetin, which has been compared to raloxifene, is the top docked score compound from the list of flavonoids; the docking score is −9.26 kcal/mol, and standard raloxifene showed −5.39 kcal/mol against epidermal growth factor receptor. The ADME profile shows the drug‐like properties. MD simulations revealed that the myricetin complex is more stable than the raloxifene complex, and pharmacophore modeling studies validated the hydrogen bonding interactions. The PASS online program predicted the biological spectrum of flavonoids against the breast cancer‐causing enzyme. Key parameters like RMSD, RMSF, RoG, hydrogen bonds, PCA, DCCM, and FEL analysis indicated better stability for myricetin. These results suggest that myricetin is a promising drug candidate against breast cancer.