Deciphering the molecular interactions of notoginsenoside L1 through DFT and multi-target docking

Notoginsenoside L1, a dammarane-type triterpenoid saponin from Panax notoginseng , is a promising bioactive compound with potential pharmacological applications. In this study, an integrated in silico approach combining Density Functional Theory (DFT) and molecular docking was employed to investigate its structural, electronic, and biological properties. B3LYP/6-311G/(d, p) level were utilised for DFT calculations to confirm molecular stability, while Natural Bond Orbital (NBO) and Molecular Electrostatic Potential (MEP) analyses revealed distinct electron-rich and electron-deficient regions. The HOMO–LUMO energy gap (4.759 eV) indicated moderate reactivity and good kinetic stability. Molecular docking studies demonstrated that Notoginsenoside L1 exhibits binding affinity toward bacterial virulence proteins, including LuxS (− 4.63 kcal/mol) and α-hemolysin (− 5.24 kcal/mol), suggesting potential anti-virulence and quorum-sensing inhibitory activity. Notably, stronger binding was observed with anticancer targets, particularly EGFR (− 8.31 kcal/mol), indicating effective inhibition of kinase activity, while moderate interaction was observed with BCL-2 (− 4.05 kcal/mol). The interactions were predominantly stabilized by hydrogen bonding and van der Waals forces. Overall, the findings highlight Notoginsenoside L1 as a potential multi-target therapeutic candidate with antibacterial and anticancer properties, supporting its further development in drug discovery.