Predicting Relative Protein Affinity of Novel Per- and Polyfluoroalkyl Substances (PFASs) by An Efficient Molecular Dynamics Approach
Predicting Relative Protein Affinity of Novel Per- and Polyfluoroalkyl Substances (PFASs) by An Efficient Molecular Dynamics Approach
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DOI：
10.1021/acs.est.8b01268
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发表时间：
2018-07-17
影响因子：
11.4
通讯作者：
Ng, Carla A.
中科院分区：
文献类型：
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作者：
Cheng, Weixiao;Ng, Carla A.
随着长链全氟烷基和多氟烷基物质（PFAS）的逐步淘汰，各种替代PFAS的生产增加，以满足市场需求。然而，人们对这些替代化合物的生物累积潜力知之甚少。在这里，我们开发了一个建模工作流程，结合分子对接和分子动力学模拟技术，以估计相对结合亲和力的共15个传统和替代PFAS的人类和大鼠肝型脂肪酸结合蛋白（hLFABP和rLFABP）。预测结果进行了比较，从三个不同的研究中提取的实验数据。预测的结合自由能和测得的结合亲和力之间有很好的相关性，相关系数分别为0.97，0.79和0.96。对于替代PFAS，我们的结果表明，EEA和ADONA至少与全氟庚酸（PFHpA）一样强烈地结合到rLFABP上，并且与全氟辛酸（PFOA）一样强烈地结合到hLFABP上。F-53和F-53 B的结合亲和力与全氟辛烷磺酸盐（PFOS）相似或更强。考虑到PFAS与蛋白质的相互作用（例如，LFABP 5）是生物体内生物累积潜力的重要决定因素，这些替代品可能与传统全氟辛烷磺酸一样具有生物累积性，因此不一定是长链全氟辛烷磺酸的更安全替代品。
With the phasing out of long-chain per- and polyfluoroalkyl substances (PFASs), production of a wide variety of alternative PFASs has increased to meet market demand. However, little is known about the bioaccumulation potential of these replacement compounds. Here, we developed a modeling workflow that combines molecular docking and molecular dynamics simulation techniques to estimate the relative binding affinity of a total of 15 legacy and replacement PFASs for human and rat liver-type fatty acid binding protein (hLFABP and rLFABP). The predicted results were compared with experimental data extracted from three different studies. There was good correlation between predicted free energies of binding and measured binding affinities, with correlation coefficients of 0.97, 0.79, and 0.96, respectively. With respect to replacement PFASs, our results suggest that EEA and ADONA are at least as strongly bound to rLFABP as perfluoroheptanoic acid (PFHpA), and as strongly bound to hLFABP as perfluorooctanoic acid (PFOA). For F-53 and F-53B, both have similar or stronger binding affinities than perfluorooctanesulfonate (PFOS). Given that interactions of PFASs with proteins (e.g., LFABP5) are important determinants of bioaccumulation potential in organisms, these alternatives could be as bioaccumulative as legacy PFASs, and are therefore not necessarily safer alternatives to long-chain PFASs.