Study of the Binding Mode of Quaternary Ammonium Cationic Surfactant to Firefly Luciferase and the Prediction of Binary Mixture Toxicity

The wide use of quaternary ammonium cationic surfactants (QACs) results in their release into the environment. Most surfactants have significant biotoxicity. However, existing toxicity data on QACs are still lacking, especially regarding the joint toxic effects of their mixtures. In computer simulation technology, molecular docking technology is commonly used for studying the mode of action of receptors docking with ligands. The research of QACs mixture interaction is relatively rare, and the binding mode of QACs is unknown. In this study, molecular docking technology was applied to explore the QAC binding mode, and the concentration addition (CA) and independent action (IA) models were applied for predicting the mixture toxicity. Firefly luciferase (FLuc) was used as a macromolecular receptor, and five typical QACs: benzalkonium bromide (BLB), tetraethylammonium bromide 1(TLB), N,N,N-trimethyl-l-tetradecyl ammonium bromide (CTE), tetrabutylammonium chloride (TAC), and dodecyltrimethylammonium chloride (DTC) were used as small molecule ligands. Molecular docking technology was used to investigate the binding mode of macromolecules and small molecules. The luminescence inhibitory effects of individual compounds and binary mixture on FLuc were determined by microplate toxicity assay of luciferase. The prediction of mixture toxicity was performed by CA and IA. The results showed that the relative toxicity follows: TLB < TAC < DTC < BLB < CTE. TLB and TAC showed the BS-II binding mode, and BLB, CTE and DTC showed the BS-III binding mode. The toxicity of compounds with binding mode BS-II was less than that of those with BS-III binding mode. Not all mixtures with the same binding mode could be predicted by CA model, and the IA model did not effectively predict the toxicity of mixtures with compound with different binding modes. The mixture toxicities of QACs with the same binding mode mostly presented additive and synergistic effects, while the mixture toxic effects of QACs with different binding modes presented additive or antagonistic effects.