Structural and Binding Insights Into Carvacrol‐Lawsone Combination as an AKT1‐Targeted Strategy for Breast Cancer Therapy

This study explores the combinatorial potential of carvacrol-lawsone adduct (CALA) by analyzing its structural, electronic, and binding features against breast cancer-associated targets. Density functional theory (DFT) calculations optimized the CALA structure, revealing band gap energies of 2.036 eV (without GD3) and 1.917 eV (with GD3), suggesting favorable electronic reactivity. Molecular electrostatic potential mapping highlighted regions of charge depolarization, while Mulliken and Natural Population Analyses provided insights into atomic charge distribution. The electronic topology was further characterized using the electron localization function (ELF) and localized orbital locator (LOL), whereas reduced density gradient (RDG) and non-covalent interaction (NCI) analyses clarified intermolecular interactions. Pharmacokinetic predictions indicated drug-like properties, and molecular docking revealed strong affinity of CALA toward AKT1 with a binding energy of -11.4 kcal/mol. Molecular dynamics simulations supported the stability of the CALA+AKT1 complex, showing consistent root mean square deviation (RMSD) values (2.5-3.0 Å) and root mean square fluctuation (RMSF) below 3.0 Å. Collectively, CALA demonstrates favorable reactivity, structural stability, pharmacological potential, and strong AKT1 interaction. These findings propose CALA as a promising combinatorial candidate for targeting AKT1 to inhibit breast cancer progression, although further in vitro and in vivo validation is necessary to establish its therapeutic applicability.