Accurate prediction of molecular properties, such as physicochemical and bioactive properties, as well as ADME/T (absorption, distribution, metabolism, excretion and toxicity) properties, remains a fundamental challenge for molecular design, especially for drug design and discovery. In this study, we advanced a novel deep learning architecture, termed FP-GNN (fingerprints and graph neural networks), which combined and simultaneously learned information from molecular graphs and fingerprints for molecular property prediction. To evaluate the FP-GNN model, we conducted experiments on 13 public datasets, an unbiased LIT-PCBA dataset and 14 phenotypic screening datasets for breast cell lines. Extensive evaluation results showed that compared to advanced deep learning and conventional machine learning algorithms, the FP-GNN algorithm achieved state-of-the-art performance on these datasets. In addition, we analyzed the influence of different molecular fingerprints, and the effects of molecular graphs and molecular fingerprints on the performance of the FP-GNN model. Analysis of the anti-noise ability and interpretation ability also indicated that FP-GNN was competitive in real-world situations. Collectively, FP-GNN algorithm can assist chemists, biologists and pharmacists in predicting and discovering better molecules with desired functions or properties.

PARP (poly ADP-ribose polymerase) family is a crucial DNA repair enzyme that responds to DNA damage, regulates apoptosis, and maintains genome stability; therefore, PARP inhibitors represent a promising therapeutic strategy for the treatment of various human diseases including COVID-19. In this study, a multi-task FP-GNN (Fingerprint and Graph Neural Networks) deep learning framework was proposed to predict the inhibitory activity of molecules against four PARP isoforms (PARP-1, PARP-2, PARP-5A, and PARP-5B). Compared with baseline predictive models based on four conventional machine learning methods such as RF, SVM, XGBoost, and LR as well as six deep learning algorithms such as DNN, Attentive FP, MPNN, GAT, GCN, and D-MPNN, the evaluation results indicate that the multi-task FP-GNN method achieves the best performance with the highest average BA, F1, and AUC values of 0.753 ± 0.033, 0.910 ± 0.045, and 0.888 ± 0.016 for the test set. In addition, Y-scrambling testing successfully verified that the model was not results of chance correlation. More importantly, the interpretability of the multi-task FP-GNN model enabled the identification of key structural fragments associated with the inhibition of each PARP isoform. To facilitate the use of the multi-task FP-GNN model in the field, an online webserver called PARPi-Predict and its local version software were created to predict whether compounds bear potential inhibitory activity against PARPs, thereby contributing to design and discover better selective PARP inhibitors.

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Virus infection is one of the major diseases that seriously threaten human health. To meet the growing demand for mining and sharing data resources related to antiviral drugs and to accelerate the design and discovery of new antiviral drugs, we presented an open‐access antiviral drug resource and machine learning platform (VDDB), which, to the best of our knowledge, is the first comprehensive dedicated resource for experimentally verified potential drugs/molecules based on manually curated data. Currently, VDDB highlights 848 clinical vaccines and 199 clinical antibodies, as well as over 710,000 small molecules targeting 39 medically important viruses including severe acute respiratory syndrome coronavirus 2. Furthermore, VDDB stores approximately three million records of pharmacological data for these collected potential antiviral drugs/molecules, involving 314 cell infection‐based phenotypic and 234 target‐based genotypic assays. Based on these annotated pharmacological data, VDDB allows users to browse, search, and download reliable information about these collects for various viruses of interest. In particular, VDDB also integrates 57 cell infection‐ and 117 target‐based associated high‐accuracy machine learning models to support various antivirals identification‐related tasks, such as compound activity prediction, virtual screening, drug repositioning, and target fishing. VDDB is freely accessible at https://vddb.idruglab.cn.