Integrating Molecular Docking, QSAR, q-RASAR Approaches to Predict PFAS Binding in Human Proteins & Bioconcentration
Maria Baquero
Co-Presenters: Jonelle Brown
College: The Dorothy and George Hennings College of Science, Mathematics and Technology
Major: Chemistry
Faculty Research Mentor: Supratik Kar
Abstract:
PURPOSEPerfluoroalkyl substances (PFAS) pose significant environmental and human health risks due to their persistence, bioaccumulation, and endocrine-disrupting potential. This study integrates QSAR and q-RASAR models with molecular docking to investigate the bioaccumulation and toxicity of PFAS.METHODSThirty-three PFAS used in QSAR and q-RASAR modeling were docked with key human blood proteins, Human Serum Albumin (HSA), Liver Fatty Acid Binding Protein (L-FABP), Transthyretin (TTR), and Thyroxine-binding Globulin (TBG) to assess their role in disrupting thyroid hormone transport and fatty acid metabolism. An external dataset of 2,522 PFAS was further analyzed using q-RASAR predictions combined with docking results to evaluate binding affinities and identify toxic potential.CONCLUSIONThe combined approach revealed 100 PFAS from the external set with the highest toxicity, highlighting the relationship between molecular descriptors, protein interactions, and bioaccumulation.SIGNIFICANCE/NOVELTYThis study offers critical insights into the toxicodynamic mechanisms of PFAS, providing a robust framework for predicting environmental and health risks while supporting future regulatory assessments and mitigation strategies.