Study on the Interaction Mechanisms and Antibacterial Properties of BSA/LF with SAP and LF with DTAB

Protein-bioactive molecule interactions are fundamental to both physiological regulation and the design of advanced biofunctional systems. To address the pressing need for highly effective, low-toxicity natural antimicrobials, this work systematically examines the multi-scale interactions and antibacterial properties of model protein bovine serum albumin (BSA) and functional protein lactoferrin (LF) with natural saponin (SAP), as well as LF with the cationic surfactant dodecyltrimethylammonium bromide (DTAB). By combining UV-Vis and fluorescence spectroscopy with molecular docking, we elucidate conformation-driven structural dynamics mediated by intermolecular forces. Hydrogen bonding and hydrophobic interactions cooperatively stabilize the BSA-SAP complex, leading to a reduction in α-helical content and increased hydrophobicity around tryptophan residues. LF–SAP association is governed by a combination of hydrogen bonding, van der Waals, and hydrophobic forces. Notably, DTAB binding to LF, driven by hydrogen bonding and hydrophobic interactions, induces significant conformational reorganization. Antibacterial assays demonstrate that the LF-DTAB complex exhibits strong synergistic activity against both E. coli and S. aureus , with notably enhanced efficacy against the latter. This selectivity is likely attributable to the DTAB-induced conformational state of LF and its differential affinity toward bacterial cell-wall components, possibly involving electrostatic and hydrophobic interactions. Our findings propose a protein-ligand synergy strategy to overcome limitations of single-agent antimicrobials, providing a molecular framework for the design of next-generation colloidal antimicrobial systems.