Study on the molecular mechanism of interaction between brominated flame retardants and human serum albumin by molecular docking

With the extensive application of brominated flame retardants (BFRs) in industry and daily life, their potential impact on human health has gradually drawn attention. This study utilized molecular docking, supplemented by molecular dynamics (MD) simulations, to analyze the interaction mechanism between various BFRs and human serum albumin (HSA). The docking results showed that the binding energy values were generally between −6.32 kcal·mol−1 and −10.98 kcal·mol−1. BFRs mainly anchored to HSA through hydrophobic interactions, hydrogen bonds, and halogen bonds. High-frequency amino acid residues such as PHE104A, LEU70A, and ILE73A repeatedly appeared in multiple docking models, suggesting their core role in the binding process. MD simulations further confirmed the stability of the representative complexes, with protein backbone RMSD values remained 0.20–0.45 nm throughout the 100 ns trajectories, corroborating the reliability of the docking-derived binding poses. Correlation analysis revealed that the physicochemical determinants of binding affinity were subclass-dependent: for PBBs, molecular weight exhibited a significant positive correlation (r = 0.646, p ≤ 0.05), while for PBDEs, density showed the strongest association (r = 0.5045, p ≤ 0.05). These findings indicate that simple bivariate correlations may not fully capture the complex binding mechanisms, and that subclass-specific rather than universal physicochemical predictors should be considered. This study provided a reusable standardized protocol for the research on the interaction between environmental pollutants and biological macromolecules and laid a theoretical foundation for the ecological risk assessment of flame retardants.