The molecular/protein-protein docking and the index normalization method assisted by the entropy weight method were used to quantitatively evaluate the biodegradability of fluoroquinolones (FQs) under different biodegradation systems. Four biodegradability three-dimensional quantitative structure-activity relationship (3D-QSAR) models of FQs were constructed to design FQ derivatives with improved biodegradability. Through the evaluation of the environmental friendliness and functional properties, the FQ derivatives with high biodegradability, improved functionality, and environmental friendliness were screened. Moreover, four bio-enhanced degradation scenarios of FQs were set up according to the different temperatures and carbon-nitrogen ratio (C/N) in the sewage sludge composting stage, and the molecular dynamic (MD) simulation assisted by protein-protein docking was used to screen the external environmental factors that promote the degradation of FQs by thermophilic bacteria or group under different scenarios. Finally, MD simulation assisted by sampling method was used to validate and screen the application scheme of field measures to enhance the expression of antibacterial resistance of FQ derivatives in an agricultural soil environment after activated sludge land use. This study aims to provide theoretical support for the development of highly biodegradable FQ derivatives and the mitigation of potential risks that FQs may pose to the environment and humans through the food chain.
Keywords: 3D-QSAR; MD simulation; biodegradation; fluoroquinolones; resistance genes; sewage sludge composting.