2ⁿᵈ Edition of the Cancer R&D World Conference 2026

Abstract

Quercetin, a naturally occurring flavonoid widely distributed in medicinal plants, has been reported to exhibit significant anticancer activity through modulation of multiple signaling pathways. To gain deeper molecular insights into its inhibitory mechanism against casein kinase II (CK2), an integrated computational approach was employed combining molecular docking, molecular dynamics (MD) simulations, MM/GBSA free energy analysis, and quantum chemical calculations. Docking results revealed that quercetin tightly occupies the ATP-binding pocket of CK2 and forms strong hydrogen bonding interactions, particularly with GLU80, indicating a potential competitive inhibition pattern. The 200 ns MD simulation confirmed the structural stability of the quercetin–CK2 complex, as reflected by stable RMSD, compact radius of gyration, and consistent hydrogen bond occupancy. Binding free energy decomposition highlighted van der Waals and electrostatic interactions as dominant stabilizing forces, while the free energy landscape illustrated a single deep minimum corresponding to a thermodynamically favorable conformation. These findings collectively suggest that quercetin achieves potent and stable inhibition of CK2 through a combination of hydrogen bonding and hydrophobic interactions, thereby interfering with CK2-mediated oncogenic signaling. This work provides valuable theoretical support for understanding the anticancer mechanism of quercetin and offers a rational basis for the development of CK2-targeted therapeutic agents derived from natural products.