Predicating macroscopic influences of drugs on human body, like efficacy and toxicity, is a central problem of small-molecule based drug discovery. Molecules can be represented as an undirected graph, and we can utilize graph convolution networks to predication molecular properties. However, graph convolutional networks and other graph neural networks all focus on learning node-level representation rather than graph-level representation. Previous works simply sum all feature vectors for all nodes in the graph to obtain the graph feature vector for drug predication. In this paper, we introduce a dummy super node that is connected with all nodes in the graph by a directed edge as the representation of the graph and modify the graph operation to help the dummy super node learn graph-level feature. Thus, we can handle graph-level classification and regression in the same way as node-level classification and regression. In addition, we apply focal loss to address class imbalance in drug datasets. The experiments on MoleculeNet show that our method can effectively improve the performance of molecular properties predication.
Neural networks are being used to make new types of empirical chemical models as inexpensive as force fields, but with accuracy similar to the ab initio methods used to build them. In this work, we present a neural network that predicts the energies of molecules as a sum of intrinsic bond energies. The network learns the total energies of the popular GDB9 database to a competitive MAE of 0.94 kcal mol on molecules outside of its training set, is naturally linearly scaling, and applicable to molecules consisting of thousands of bonds. More importantly, it gives chemical insight into the relative strengths of bonds as a function of their molecular environment, despite only being trained on total energy information. We show that the network makes predictions of relative bond strengths in good agreement with measured trends and human predictions. A Bonds-in-Molecules Neural Network (BIM-NN) learns heuristic relative bond strengths like expert synthetic chemists, and compares well with ab initio bond order mea...  Molecular machine learning has been maturing rapidly over the last few years. Improved methods and the presence of larger datasets have enabled machine learning algorithms to make increasingly accurate predictions about molecular properties. However, algorithmic progress has been limited due to the lack of a standard benchmark to compare the efficacy of proposed methods; most new algorithms are benchmarked on different datasets making it challenging to gauge the quality of proposed methods. This work introduces MoleculeNet, a large scale benchmark for molecular machine learning. MoleculeNet curates multiple public datasets, establishes metrics for evaluation, and offers high quality open-source implementations of multiple previously proposed molecular featurization and learning algorithms (released as part of the DeepChem open source library). MoleculeNet benchmarks demonstrate that learnable representations are powerful tools for molecular machine learning and broadly offer the best performance. However, this result comes with caveats. Learnable representations still struggle to deal with complex tasks under data scarcity and highly imbalanced classification. For quantum mechanical and biophysical datasets, the use of physics-aware featurizations can be more important than choice of particular learning algorithm. Numerous important problems can be framed as learning from graph data. We propose a framework for learning convolutional neural networks for arbitrary graphs. These graphs may be undirected, directed, and with both discrete and continuous node and edge attributes. Analogous to image-based convolutional networks that operate on locally connected regions of the input, we present a general approach to extracting locally connected regions from graphs. Using established benchmark data sets, we demonstrate that the learned feature representations are competitive with state of the art graph kernels and that their computation is highly efficient.  Massively multitask neural architectures provide a learning framework for drug discovery that synthesizes information from many distinct biological sources. To train these architectures at scale, we gather large amounts of data from public sources to create a dataset of nearly 40 million measurements across more than 200 biological targets. We investigate several aspects of the multitask framework by performing a series of empirical studies and obtain some interesting results: (1) massively multitask networks obtain predictive accuracies significantly better than single-task methods, (2) the predictive power of multitask networks improves as additional tasks and data are added, (3) the total amount of data and the total number of tasks both contribute significantly to multitask improvement, and (4) multitask networks afford limited transferability to tasks not in the training set. Our results underscore the need for greater data sharing and further algorithmic innovation to accelerate the drug discovery process. Empirical scoring functions based on either molecular force fields or cheminformatics descriptors are widely used, in conjunction with molecular docking, during the early stages of drug discovery to predict potency and binding affinity of a drug-like molecule to a given target. These models require expert-level knowledge of physical chemistry and biology to be encoded as hand-tuned parameters or features rather than allowing the underlying model to select features in a data-driven procedure. Here, we develop a general 3-dimensional spatial convolution operation for learning atomic-level chemical interactions directly from atomic coordinates and demonstrate its application to structure-based bioactivity prediction. The atomic convolutional neural network is trained to predict the experimentally determined binding affinity of a protein-ligand complex by direct calculation of the energy associated with the complex, protein, and ligand given the crystal structure of the binding pose. Non-covalent interactions present in the complex that are absent in the protein-ligand sub-structures are identified and the model learns the interaction strength associated with these features. We test our model by predicting the binding free energy of a subset of protein-ligand complexes found in the PDBBind dataset and compare with state-of-the-art cheminformatics and machine learning-based approaches. We find that all methods achieve experimental accuracy and that atomic convolutional networks either outperform or perform competitively with the cheminformatics based methods. Unlike all previous protein-ligand prediction systems, atomic convolutional networks are end-to-end and fully-differentiable. They represent a new data-driven, physics-based deep learning model paradigm that offers a strong foundation for future improvements in structure-based bioactivity prediction.