Using molecular docking-based binding energy to predict toxicity of binary mixture with different binding sites

• Published in: Chemosphere (Oxford) Vol. 92; no. 9; pp. 1169 - 1176
• Main Authors: Yao, Zhifeng, Lin, Zhifen, Wang, Ting, Tian, Dayong, Zou, Xiaoming, Gao, Ya, Yin, Daqiang
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.08.2013; Elsevier
• Subjects: aldehydes; Aldehydes - chemistry; Aldehydes - metabolism; Aldehydes - toxicity; Animal, plant and microbial ecology; Applied ecology; Binary mixtures; Binding Sites; Biological and medical sciences; Ecotoxicology, biological effects of pollution; energy; Fundamental and applied biological sciences. Psychology; herbicides; Herbicides - chemistry; Herbicides - metabolism; Herbicides - toxicity; Kinetics; Luciferases, Bacterial - chemistry; Luciferases, Bacterial - metabolism; Molecular docking energy; Molecular Docking Simulation; Nitriles - chemistry; Nitriles - metabolism; Nitriles - toxicity; Organic Chemicals - chemistry; Organic Chemicals - metabolism; Organic Chemicals - toxicity; Photobacterium - drug effects; Photobacterium - enzymology; Protein Structure, Tertiary; proteins; Quantitative Structure-Activity Relationship; sulfonamides; Sulfonamides - chemistry; Sulfonamides - metabolism; Sulfonamides - toxicity; Techniques; Thermodynamics; toxic substances; toxicity; Toxicity model; Toxicity Tests; triazines; Triazines - chemistry; Triazines - metabolism; Triazines - toxicity; trimethoprim; Trimethoprim - chemistry; Trimethoprim - metabolism; Trimethoprim - toxicity; urea; Urea - chemistry; Urea - metabolism; Urea - toxicity; TU; Dhps; Toxicity model; AHs; TZs; Binary mixtures; SA; CGs; Dhfr; UE; TMP; Luc; Molecular docking energy; Binding sites; Photobacterium phosphoreum; Poison interaction; Toxicity; Algae; Chemical compound; Prediction; Binding site; Chlorophyceae; Selenastrum capricornutum; Modeling; Toxic association; Binary mixture; Chlorophyta; Structure activity relation; Binding energy; Molecular model; Bacteria; Vibrionaceae; Thermodynamic properties; dihydrofolate synthase; urea; aldehydes; triazines; sulfonamide; trimethoprim; luciferase; cyanogenic; dihydropteroate reductase; toxicity unit
• ISSN: 0045-6535; 1879-1298
• DOI: 10.1016/j.chemosphere.2013.01.081

► We analyze toxicity process of single chemicals and their corresponding mixtures. ► We approximately quantify the toxicity effect of mixtures. ► We propose a QSAR model, even individual chemicals bind to different binding sites. The flood of chemical substances in the environment result in the complexity of chemical mixtures, and one of the reasons for complexity is that their individual chemicals bind to different binding sites on different (or same) target proteins within the organism. A general approaches therefore are proposed in this study to predict the toxicity of chemical mixtures with different binding sites by using molecular docking-based binding energy (Ebinding). Aldehydes and cyanogenic toxicants were selected as the example of chemical mixtures with same binding site. Triazines and urea herbicide were selected as the example of chemical mixtures with different binding sites but on same target protein. Sulfonamides and trimethoprim toxicants were selected as the example of chemical mixtures with different target proteins. Although these chemical mixtures bind to their binding sites by different ways, there is a general relationship between their binary mixture toxicity (EC50M) and their corresponding Ebinding of individual chemicals and logKow(mix). By using the Ebinding to describe how the individual chemicals work in the different binding sites, the approach may provide a general and simply model to predict mixture toxicity to microorganism.