Conceptual DFT, machine learning and molecular docking as tools for predicting LD₅₀ toxicity of organothiophosphates

Several descriptors from conceptual density functional theory (cDFT) and the quantum theory of atoms in molecules (QTAIM) were utilized in Random Forest (RF), LASSO, Ridge, Elastic Net (EN), and Support Vector Machines (SVM) methods to predict the toxicity (LD₅₀) of sixty-two organothiophosphate compounds. The A-RF-G1 and A-RF-G2 models were obtained using the RF method, yielding statistically significant parameters with good performance, as indicated by R² values for the training set (R²_Train) and R² values for the test set (R²_Test), around 0.90.

The molecular structure of all organothiophosphates was optimized via the range-separated hybrid functional ωB97XD with the 6-311 +  + G** basis set. Seven hundred and eighty-seven descriptors have been processed using a variety of machine learning algorithms: RF LASSO, Ridge, EN and SVM to generate a predictive model. The properties were obtained with Multiwfn, AIMALL and VMD programs. Docking simulations were performed by using AutoDock 4.2 and LigPlot + programs. All the calculations in this work are carried out in Gaussian 16 program package.