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Application of 3D-QSAR Approaches to Classification and Prediction of Aquatic Toxicity
Citation:
Lee, S. AND M. Barron. Application of 3D-QSAR Approaches to Classification and Prediction of Aquatic Toxicity. Chapter 21, Chemometrics and Cheminformatics in Aquatic Toxicology. John Wiley & Sons Inc, Malden, MA, , 417-432, (2021). https://doi.org/10.1002/9781119681397.ch21
Impact/Purpose:
The purpose of the book chapter is to summarize approaches and applications of past EPA research on three dimensional quantitative structure activity relationship (3D-QSAR) models. The impact of the work is that it communicates a state of the science approach to QSAR that has the potential to revolutionize how chemicals are screened for toxicological activity and potency. Communication of the approach as a chapter in an influential book will increase the awareness of the approach and likelihood that it could be adopted in international chemical screening programs.
Description:
Three dimensional quantitative structure activity relationship (3D-QSAR) models combining 3D-pharmacophore and molecular docking offers substantial advantages over traditional ligand- and structure-based QSAR approaches, including the intrinsic capability of identifying critical protein-ligand interactions within ligand binding domains and defining their quantitative contributions to toxicity. The approach is generally universal with definable and less constrained domains of applicability. The ability both to identify key amino acid residues necessary for chemical potency and biological activity and to extrapolate species sensitivity based on amino acid substitutions provides a powerful tool for predicting and extrapolate species sensitivity.are extensively used in drug design, but have seen only limited applications in chemical classification and prediction of aquatic toxicity. High levels of expertise and rigorous model development are required, and ultimately cross-species extrapolation will be limited by the available crystal structures. Additional research and application of 3D-QSAR modeling to current challenges in aquatic toxicity estimation including for emerging chemicals and for endangered and other less tested species is highly recommended.
URLs/Downloads:
DOI: Application of 3D-QSAR Approaches to Classification and Prediction of Aquatic Toxicity