PointGAT: A Quantum Chemical Property Prediction Model Integrating Graph Attention and 3D Geometry.

Abstract

Predicting quantum chemical properties is a fundamental challenge for computational chemistry. While the development of graph neural networks has advanced molecular representation learning and property prediction, their performance could be further enhanced by incorporating three-dimensional (3D) structural geometry into two-dimensional (2D) molecular graph representation. In this study, we introduce the PointGAT model for quantum molecular property prediction, which integrates 3D molecular coordinates with graph-attention modeling. Comparison with other current models in molecular prediction tasks showed that PointGAT could provide higher predictive accuracy in various benchmark data sets from MoleculeNet, including ESOL, FreeSolv, Lipop, HIV, and 6 out of 12 tasks of the QM9 data set. To further examine PointGAT prediction of quantum mechanical (QM) energies, we constructed a C10 data set comprising 11,841 charged and chiral carbocation intermediates with QM energies calculated at the DM21/6-31G*//B3LYP/6-31G* levels. Notably, PointGAT achieved an R2 value of 0.950 and an MAE of 1.616 kcal/mol, outperforming even the best-performing graph neural network model with a reduction of 0.216 kcal/mol in MAE and an improvement of 0.050 in R2. Additional ablation studies indicated that incorporating molecular geometry into the model resulted in markedly higher predictive accuracy, reducing the MAE value from 1.802 to 1.616 kcal/mol. Moreover, visualization of PointGAT atomic attention weights suggested its predictions were interpretable. Findings in this study support the application of PointGAT as a powerful and versatile tool for quantum chemical property prediction that can facilitate high-accuracy modeling for fundamental exploration of chemical space as well as drug design and molecular engineering.