Binding Affinity and Mechanism of Six PFAS with Human Serum Albumin: Insights from Multi-Spectroscopy, DFT and Molecular Dynamics Approaches

作者：Mingguo Peng, Yang Xu, Yao Wu, Xuewen Cai, Weihua Zhang, Zheng Lu, Erdeng Du, Jiajun Fu · 发表于：Toxics · 年份：2024 · DOI：10.3390/toxics12010043 · 被引用次数：43 · 研究领域：Per- and polyfluoroalkyl substances research、Protein Interaction Studies and Fluorescence Analysis、Photochemistry and Electron Transfer Studies

Per- and Polyfluoroalkyl Substances (PFAS) bioaccumulate in the human body, presenting potential health risks and cellular toxicity. Their transport mechanisms and interactions with tissues and the circulatory system require further investigation. This study investigates the interaction mechanisms of six PFAS with Human Serum Albumin (HSA) using multi-spectroscopy, DFT and a molecular dynamics approach. Multi-spectral analysis shows that perfluorononanoic acid (PFNA) has the best binding capabilities with HSA. The order of binding constants (298 K) is as follows: “Perfluorononanoic Acid (PFNA, 7.81 × 106 L·mol−1) > Perfluoro-2,5-dimethyl-3,6-dioxanonanoic Acid (HFPO-TA, 3.70 × 106 L·mol−1) > Perfluorooctanoic Acid (PFOA, 2.27 × 105 L·mol−1) > Perfluoro-3,6,9-trioxadecanoic Acid (PFO3DA, 1.59 × 105 L·mol−1) > Perfluoroheptanoic Acid (PFHpA, 4.53 × 103 L·mol−1) > Dodecafluorosuberic Acid (DFSA, 1.52 × 103 L·mol−1)”. Thermodynamic analysis suggests that PFNA and PFO3DA’s interactions with HSA are exothermic, driven primarily by hydrogen bonds or van der Waals interactions. PFHpA, DFSA, PFOA, and HFPO-TA’s interactions with HSA, on the other hand, are endothermic processes primarily driven by hydrophobic interactions. Competitive probe results show that the main HSA–PFAS binding site is in the HSA structure’s subdomain IIA. These findings are also consistent with the findings of molecular docking. Molecular dynamics simulation (MD) analysis further shows that the l...