LAUSR

Abstract Environmental enrichment abilities and chronic sub-lethal effects on non-target organisms caused by neonicotinoid insecticides (neonics) have been challenging issues for environmental pollution. In other words, the renewal of insecticides, especially the research of green substitutes, is one of the best ways to protect the environment and non-target organisms. In this research, a complete design and screening system for green substitutes of neonics was established through the contour map, homology modeling, molecular docking, and molecular dynamics. Contour maps were constructed to obtain the substituted sites and groups, and the results revealed that introducing large, negative/positive or hydrophobic groups can reduce the enrichment abilities of neonics. Using Compound 18 as a template, 58 derivatives with lower enrichment abilities were designed (decreased by 0.55%–57.42%). Then, human health risks were assessed based on multimedia exposure model of pollutants, and the HI values of five derivatives were found to be