Biodegradability analysis of Dioxins through in silico methods: Model construction and mechanism analysis

The biodegradation treatment of dioxins has long been of interest due to its good ecological and economic effects. In this study, the biodegradability of polychlorinated dibenzo-p-dioxins (PCDDs) were investigated by constructing machine learning and multiple linear regression models. The maximum chlorine atomic charge (q_HirshfeldCl⁺), which characterizes the biodegradation ability of PCDDs, was used as the response value. The random forest model was used to rank the importance on the 1471 descriptors of PCDDs, and the BCUTp-1 h, Q_XZ, JGI4, ATSC8c, VE3_Dt, topoShape, and maxwHBa were screened as the important descriptors by Pearson's correlation coefficient method. A quantitative structure-activity relationship (QSAR) model was constructed to predict the biodegradability of PCDDs. In addition, the extreme gradient boosting (XGBoost) and random forest model were also constructed and proved the good predictability of QSAR model. The biodegradability of polychlorinated dibenzofurans (PCDFs) can also be predicted by the constructed three models from a certain level after adjusting some model parameters, which further proved the versatility of the models. Besides, the sensitivity analysis of the QSAR model and a 3D-QSAR model was developed to investigate the biodegradability mechanisms of PCDDs. Results showed that the descriptors BCUTp-1 h, JGI4, and maxwHBa were the key descriptors in the biodegradability effect by the sensitivity analysis of the QSAR model. Coupled with the results of PCDDs biodegradability 3D-QSAR model, BCUTp-1 h, JGI4, and maxwHBa were confirmed as the main descriptors that affect the biodegradability of dioxins. This study provides a novel theoretical perspective for the research of the biodegradation of both PCDDs and PCDFs dioxins.