Integrated DFT and Molecular Docking Study on the Reactivity and Binding Behavior of Molecule 472D Toward Target Proteins

An integrated density functional theory (DFT) and molecular docking approach has beenemployed to systematically investigate the reactivity profile and protein binding behavior of molecule 472D. The optimized molecular geometry of 472D was obtained using the B3LYP functional with an appropriate basis set, ensuring a reliable description of its ground-state structure. The electronic properties were analyzed through frontier molecular orbital (HOMO–LUMO) analysis, molecular electrostatic potential mapping, and global reactivity descriptors, including chemical hardness, softness, electronegativity, chemical potential, and electrophilicity index. The calculated results reveal significant charge delocalization and a moderate HOMO–LUMO energy gap, indicating favorable chemical stability coupled with appreciable reactivity.To explore the biological relevance of molecule 472D, molecular docking simulations were performed against selected target proteins using a validated docking protocol. The docking results demonstrate strong binding affinity, characterized by low binding energy values and stable ligand–protein complexes. Detailed interaction analysis reveals that hydrogen bonding, hydrophobic interactions, and π–π stacking interactions play a crucial role in stabilizing the ligand within the active site of the target proteins. The binding orientation of molecule 472D correlates well with its electronic distribution, suggesting that frontier orbitals and electrostatic potential regions significantly influence molecular recognition.Overall, the combined DFT and molecular docking results provide valuable insights into the structure–reactivity–binding relationship of molecule 472D. This study highlights the potential of molecule 472D as a promising candidate for further experimental validation and rational drug design applications.