Molecular docking and dynamics of natural compounds targeting iron and erythropoietic pathways in β-Thalassemia

β-Thalassemia is characterized by ineffective erythropoiesis and systemic iron overload, creating major therapeutic challenges. This study screened 114 phytochemicals against ferroportin (FPN), transferrin receptor 1 (TfR1), and activin receptors ACVR2A and ACVR2B using molecular docking and molecular dynamics approaches. Oleanolic acid (OA) ranked highest, showing strong docking affinities for FPN (-9.7 kcal/mol) and TfR1 (-10.4 kcal/mol). Subsequent 100-ns MD simulations and MM/GBSA calculations confirmed stable and energetically favorable binding, with binding free energies of -44.88 ± 4.22 kcal/mol for FPN and -41.45 ± 5.75 kcal/mol for TfR1, supported by persistent hydrogen-bonding and hydrophobic interactions. In contrast, OA displayed unstable interactions and unfavorable energy profiles with ACVR2A and ACVR2B. In silico ADME predictions indicated high oral bioavailability and favorable drug-likeness. These findings identify OA as a promising dual modulator of iron export and iron uptake pathways, warranting in vivo validation and further evaluation in β-thalassemia therapeutic frameworks.