Identification of kaempferol as a potent estrogen receptor-α antagonist for therapeutic applications: integrating molecular docking, MD simulations, and DFT calculations

Kaempferol was systematically evaluated as a potential ER-α inhibitor using an integrated computational workflow including ADMET profiling, DFT calculations, molecular docking, 500 ns molecular dynamics simulations, and MM/GBSA binding free energy analysis. ADMET results indicated favorable oral bioavailability, low toxicity risk, and structural stability. DFT analysis revealed strong chemical stability with a HOMO-LUMO gap of 9.84 eV. Docking and MD simulations demonstrated stable binding within the ER-α active site over 500 ns, with limited structural fluctuations and a stable energy landscape. MM/GBSA confirmed strong binding affinity (ΔGbind = -36.01 kcal/mol). Key residues such as GLU-353 and HIE-524 contributed to electrostatic interactions, while PHE-404 and LEU-346 stabilized hydrophobic contacts, supporting Kaempferol as a promising ER-α targeting lead for breast cancer therapy.