PDF(Pubmed)
Abstract：
Per- and poly-fluorinated compounds constitute a wide group of fluorocarbon chemicals with widespread industrial applications, ranging from non-stick coating in cookware to water surfactants, from fire-fighting foams to water-repellent coatings on textiles. Presently, over 12,000 PFAS are known worldwide. In recent years, extensive research has focused on investigating the biological effects of these molecules on various organisms, including humans. Here, we conducted in silico simulations to examine the potential binding of a representative selection of PFAS to various human proteins known to be involved in chemical transportation and accumulation processes. Specifically, we targeted human serum albumin (HSA), transthyretin (TTR), thyroxine binding protein (TBG), fatty acid binding proteins (FABPs), organic anion transporters (OATs), aiming to assess the potential for bioaccumulation. Molecular docking simulations were employed for this purpose, supplemented by molecular dynamics (MD) simulations to account for protein flexibility, when necessary. Our findings indicate that so-called \"legacy PFAS\" such as PFOA or PFOS exhibit a higher propensity for interaction with the analysed human protein targets compared to newly formulated PFAS, characterised by higher branching and hydrophilicity, and possibly a higher accumulation in the human body.
摘要：
全氟化和多氟化化合物构成了广泛的碳氟化合物化学品，具有广泛的工业应用，从炊具中的不粘涂层到水表面活性剂，从消防泡沫到纺织品上的防水涂料。目前,全球已知超过12,000个PFAS。近年来,广泛的研究集中在研究这些分子对各种生物体的生物学效应，包括人类。这里,我们进行了计算机模拟，以检查PFAS的代表性选择与已知参与化学运输和积累过程的各种人类蛋白质的潜在结合。具体来说,我们针对人血清白蛋白（HSA），转甲状腺素蛋白(TTR),甲状腺素结合蛋白（TBG），脂肪酸结合蛋白（FABP），有机阴离子转运蛋白（OATs），旨在评估生物累积的潜力。为此目的采用了分子对接模拟，补充分子动力学（MD）模拟以解释蛋白质的灵活性，必要时。我们的发现表明，与新配制的PFAS相比，所谓的“传统PFAS”如PFOA或PFOS表现出更高的与分析的人类蛋白质靶标相互作用的倾向。以更高的支化和亲水性为特征，并可能在人体中积累更多。
