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Bioanalytical methods targeting adverse cellular outcomes are increasingly used in environmental toxicology, including receptor-mediated toxicity pathways relevant to high-throughput monitoring of drinking water, wastewater, and other environmental samples. However, despite their increasing regulatory acceptance, the representativeness of human tissue-derived bioassays for assessing toxicity toward aquatic species remains uncertain. Given these circumstances, this data article presents molecular docking and sequence-alignment datasets generated to compare human and zebrafish receptor/sensor variants associated with the oxidative stress response (Keap1/Nrf2) and xenobiotic metabolism (AhR/ARNT) pathways. The dataset includes docking data for hKeap1, zfKeap1a, and zfKeap1b, as well as hAhR, zfAhR1a, zfAhR1b, and zfAhR2 receptor/sensor variants, with selected reference ligands and environmental pollutants. Receptor/sensor protein structures derived from AlphaFold predictions, X-ray crystallography, or cryo-electron microscopy were retrieved, prepared, and refined for molecular docking. Ligand structures included the reference agonists tetrachlorodibenzodioxin and tert-butylhydroquinone, as well as the environmental pollutants climbazole, daidzein, thiabendazole, and metazachlor. Docking was performed using AutoDock Vina, generating the best-energy poses for each ligand-protein pair within defined docking grids. AlphaFold-predicted structures were evaluated by parallel docking into available partial X-ray crystal structures of the corresponding variants. For Keap1 variants, blind and site-directed docking approaches were applied, including grids covering reactive cysteine-associated binding regions, and potential effects of Keap1 dimerisation were considered. For AhR variants, docking focused on the PAS-B ligand-binding domain. Protein sequence alignment was conducted using the ClustalW algorithm to compare human and zebrafish receptor/sensor variants and support cross-species comparison of docking outputs. The dataset comprises prepared protein and ligand files, representative docking poses, binding-affinity outputs, and sequence-alignment data. These files provide reusable input and output material for comparative toxicology, cross-species extrapolation, receptor-ligand interaction assessment, and benchmarking of molecular docking workflows. The data may inform scientists and regulators interested in molecular initiating events, toxicity-pathway conservation, and interspecies differences in receptor-mediated responses. This data article complements a related research article ( please add link after parallel review process ) by providing supporting docking data, receptor/sensor variant sequence-alignments, and quality-assurance procedures for the molecular docking workflow.
Lungu-Mitea et al. (Wed,) studied this question.