You are here:
Estimating the bioaccumulation potential of per-and polyfluoroalkyl substances (PFAS) across species by integrative in silico approaches
Citation:
Cheng, W., J. Doering, C. Lalone, AND C. Ng. Estimating the bioaccumulation potential of per-and polyfluoroalkyl substances (PFAS) across species by integrative in silico approaches. Allegheny-Erie Society of Toxicology Regional Chptr Modernizing Toxicity Testing/ Risk Assessment, Pittsburgh, PA, May 01 - 02, 2019.
Impact/Purpose:
Per and polyfluoroalkyl substances (PFAS) are a group of chemicals that have been widely used in industrial and consumer products and found in the environment. It is known that these substances can bioaccumulate, however there are limited data regarding their ability bioaccumulate across the diversity of species. PFAS are known to interact with certain proteins in mammals thought to be involved in their bioaccumulation potential. Therefore, understanding if these proteins are found in other organisms can provide an initial indication of whether PFAS have the potential to interact with the protein in another species and bioaccumulate. Computational tools were used in this initial study to understand how and if PFAS are likely to interact with the liver fatty acid binding protein to inform follow up cross species bioaccumulation studies.
Description:
Per and polyfluoroalkyl substances (PFAS) are a group of chemicals that have been widely used in industrial and consumer products for decades. Recent estimates suggest there are nearly 5000 PFAS on the global market. However, many of these have very little information available about their bioaccumulation potential and toxic effects, the data is even more sparse across different species. Given the vast number of PFAS, reliable in silico approaches to predict the behavior of PFAS across species would be of great benefit to environmental risk assessment. Studies have shown that the interaction between PFAS and liver fatty acid binding protein (LFABP) is a critical factor determining their bioaccumulation potential. Here, the US Environmental Protection Agency’s Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool (https://seqapass.epa.gov/seqapass/), homology modelling, molecular docking and molecular dynamics (MD) simulations were integrated to predict LFABP interactions across 7 different species, representing diverse taxonomic groups, for 9 PFAS with different chain lengths and functional groups. The SeqAPASS tool, which compares molecular target protein sequences to predict chemical susceptibility identified phenylalanine (F) at position 50 and threonine (T) at position 93 on LFABP as key amino acid residues differing across-species that may be predictive of PFAS bioaccumulation potential. MD simulation was used to calculate the protein binding free energies for different PFAS and the results indicated that after mutation of residue 93 from T to F, the human LFABP binding affinity for perfluorooctanoic acid changed significantly (p 0.05) binding affinity compared to LFABP of other species for all 9 PFAS except perfluoroheptanoic acid. Our integrative modeling study provides valuable insights into the interactions that drive differences in PFAS bioaccumulation potential across species.