Fast and accurate prediction of partial charges using Atom-Path-Descriptor-based machine learning

MOTIVATION Partial atomic charges are usually used to calculate the electrostatic component of energy in many molecular modeling applications, such as molecular docking, molecular dynamics simulations, free energy calculations, etc. High-level quantum mechanics calculations may provide the most accurate way to estimate the partial charges for small molecules, but they are too time-consuming to be used to process a large number of molecules for high throughput virtual screening. RESULTS We proposed a new molecule descriptor named Atom Path Descriptor (APD) and developed a set of APD-based machine learning (ML) models to predict the partial charges for small molecules with high accuracy. In the APD algorithm, the 3D structures of molecules were assigned with atom centers and atom-pair path-based atom layers to characterize the local chemical environments of atoms. Then, based on the APDs, two representative ensemble ML algorithms, i.e., random forest (RF) and extreme gradient boosting (XGBoost), were employed to develop the regression models for partial charge assignment. The results illustrate that the RF models based on APDs give better predictions for all the atom types than those based on traditional molecular fingerprints reported in the previous study. More encouragingly, the models trained by XGBoost can improve the predictions of partial charges further, and they can achieve the average root-mean-square error (RMSE) 0.0116 e on the external test set, which is much lower than that (0.0195 e) reported in the previous study, suggesting that the proposed algorithm is quite promising to be used in partial charge assignment with high accuracy.