Combined Semi-empirical Docking, QSAR, Molecular Dynamics, and DFT Studies for Identifying Potential Anticancer Agents in Royal Jelly

Cancer rates are expected to increase, with Src kinase playing a crucial role in cancer metabolism. This study explored bioactive compounds in royal jelly (RJ) as novel anticancer agents targeting Src kinase using computational methods. QM-AM1 was used for structure preparation, while MD simulations assessed protein-ligand stability, and advanced analyses provided post-MD data. The results indicated that, among the bioactive compounds in RJ, formononetin was promising, with a binding energy of 8.243 kcal/mol and interactions with the active sites of two Src kinase pockets. DFT calculations for formononetin suggested good stability and low reactivity. MD simulations demonstrated that the Src kinase–Formononetin complex adopted a stable, favorable binding pose, and subsequent MM-PBSA analysis indicated a markedly stronger binding affinity than that of the reference inhibitor AP23451. PCA analysis revealed overlapping energy distributions and a positive correlation between RMSDca and DCCM plots, providing insights into the stability and conformation of the Src kinase-formononetin complex. This study proposes formononetin as a novel anticancer inhibitor candidate through comprehensive in silico computational analysis, while acknowledging that further validation through in vitro and in vivo studies is required.