Computational discovery of bioactive flavonoids from Ziziphus mauritiana via integrated ADME prediction, molecular docking, DFT calculation and molecular dynamics simulation

Green jujube ( Ziziphus mauritiana ) is a rich source of flavonoids with potential therapeutic effects, yet systematic evaluation of their drug-like properties and target interactions remains limited. Hence, this study integrated network pharmacology, ADME (absorption, distribution, metabolism, excretion) profiling, molecular docking, density functional theory (DFT), and molecular dynamics (MD) simulations to screen for bioactive flavonoids and validate their interactions with disease-relevant targets. From 143 flavonoids, this study identified three lead compounds, phloretin, pinobanksin and eriodictyol, that exhibited favorable drug-likeness (zero Lipinski/Ghose/Veber/Egan/Muegge violations, high GI absorption, and bioavailability scores ≥ 0.55). These compounds bound with high affinity to three tumor-related targets: estrogen receptor alpha (ESR1), matrix metalloproteinase 13 (MMP13), and carbonic anhydrase 7 (CA7), with docking binding energies of -7.02, -8.51 and − 7.26 kcal/mol, respectively. DFT calculations revealed distinct electronic properties (HOMO–LUMO gaps: 4.36–4.53 eV) supporting their chemical stability and reactivity. MD simulations (100 ns) confirmed stable binding conformations, with average RMSD values of 0.28 nm (ESR1), 0.70 nm (MMP13), and 0.22 nm (CA7), and favorable binding free energies (MM‑GBSA: -40.97, -29.98, -28.63 kcal/mol). Collectively, this integrated computational approach identifies phloretin, pinobanksin, and eriodictyol as promising candidates for further experimental validation in cancer-related therapeutic contexts.