Comparative study on the binding of tetrabromobisphenol A/S with human hemoglobin: Spectroscopic and computational simulations techniques.

Tetrabromobisphenol A (TBBPA) and its substitute Tetrabromobisphenol S (TBBPS) are widely used flame retardants that pose diverse hazards to both the environment and human health. In this study, multi-spectroscopic and computational techniques were used to analyze the interactions between the two ligands and a multifunctional protein -human hemoglobin (HHb). The steady state fluorescence spectra demonstrated that TBBPA and TBBPS quenched HHb fluorescence by static quenching mechanism, driven by electrostatic forces. Conformational change analyses demonstrated a structural relaxation of HHb upon ligand binding. These changes likely attributed to a reduction in thiol group content, which may enhance ligand binding affinity. Molecular docking exhibited TBBPA and TBBPS occupied the same active cavity of HHb, surrounded by common and unique amino acids. Molecular dynamics (MD) simulation further confirmed the formation of stable complexes and the minor structural disturbances. Energy decomposition identified key residues (ProA:95, ThrA:137, ValC:1, LysC:99, AspC:126, LysC:127, GluD:101) stabilizing the complexes through tight binding interactions with the ligands. Among these, ValC:1 functioned as the binding site for bromine atoms, while the interaction of ligands with AspC:126 and LysC:127 could potentially modulate the oxygen-carrying capacity of HHb. Notably, the distinct binding patterns of TyrA:140 to TBBPA and LysC:99 to TBBPS were primarily attributed to the structural differences between the two ligands. By exploring the molecular interactions of HHb with brominated flame retardants (BFRs), this study provides valuable information to better understand their potential risks and informs the future design of environmentally safer alternatives.