Distinct binding affinity of perfluoroalkyl acids to plant and animal proteins revealed by dialysis experiments, fluorescence spectroscopy, and QSAR modeling

Understanding the binding dynamics between perfluoroalkyl acids (PFAAs) and proteins is crucial for risk assessment, as protein binding plays a vital role in the bioaccumulation of PFAAs. This study employed dialysis experiments to measure the protein-water partition coefficient of PFAAs with representative plant and animal proteins, including standard bovine serum albumin, soy protein isolate, and C-phycocyanin. Fluorescence spectroscopy was investigated to elucidate the binding affinity of PFAAs on bovine serum albumin (BSA). Additionally, through the construction of the quantitative structure-activity relationship (QSAR) model, this research comprehensively analyzed the binding characteristics of various PFAAs to proteins, offering insights into the molecular mechanisms of PFAAs-protein interactions. The results revealed that the binding capacity of bovine serum albumin for PFAAs was significantly superior to that of C-phycocyanin and soy protein isolate. Electrostatic attraction was the predominant factor influencing the interaction between proteins and PFAAs. The binding of PFAAs to proteins was chiefly mediated by tryptophan residues, and there was no notable change in the protein conformation pre- and post-binding. Finally, the QSAR models, constructed with energy gap (E_gap) between the highest occupied and the lowest unoccupied molecular orbitals, the net charge of the most negative atom (q), and ionic volume as descriptors, suggested that the hydrophobic interactions, electrostatic interactions, and the stability of PFAA molecule are key factors affecting PFAA-protein binding. This study enhances our comprehension of the binding capacity of animal and plant proteins to PFAAs, while also establishing a foundation for future research on the binding of emerging PFAA alternatives to proteins.