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.
@cite_5 propose graph convolutional network that operates directly on graph, which could learn better representations than conventional method like ECFP. @cite_21 combine graph convolutional network with residual LSTM embedding for one-shot learning on drug discovery. @cite_22 @cite_10 apply neural network to predicate the molecular energy and reduced the predication error to 1 kcal mol. @cite_11 propose atomic neural network to predicate the binding free energy of a subset of protein-ligand complexes found in the PDBBind dataset. @cite_20 applied Massively multitask neural architectures to synthesize information from many distinct biological sources. @cite_6 introduce MoleculeNet, a large scale benchmark for molecular machine learning, which contains multiple public datasets, and establish metrics for evaluation and high quality open-source implementations.
@cite_22 @cite_21 @cite_6 @cite_5 @cite_10 @cite_20 @cite_11
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Convolutional neural networks (CNNs) have achieved great success on grid-like data such as images, but face tremendous challenges in learning from more generic data such as graphs. In CNNs, the trainable local filters enable the automatic extraction of high-level features. The computation with filters requires a fixed number of ordered units in the receptive fields. However, the number of neighboring units is neither fixed nor are they ordered in generic graphs, thereby hindering the applications of convolutional operations. Here, we address these challenges by proposing the learnable graph convolutional layer (LGCL). LGCL automatically selects a fixed number of neighboring nodes for each feature based on value ranking in order to transform graph data into grid-like structures in 1-D format, thereby enabling the use of regular convolutional operations on generic graphs. To enable model training on large-scale graphs, we propose a sub-graph training method to reduce the excessive memory and computational resource requirements suffered by prior methods on graph convolutions. Our experimental results on node classification tasks in both transductive and inductive learning settings demonstrate that our methods can achieve consistently better performance on the Cora, Citeseer, Pubmed citation network, and protein-protein interaction network datasets. Our results also indicate that the proposed methods using sub-graph training strategy are more efficient as compared to prior approaches. Recently, neuron activations extracted from a pre-trained convolutional neural network (CNN) show promising performance in various visual tasks. However, due to the domain and task bias, using the features generated from the model pre-trained for image classification as image representations for instance retrieval is problematic. In this paper, we propose quartet-net learning to improve the discriminative power of CNN features for instance retrieval. The general idea is to map the features into a space where the image similarity can be better evaluated. Our network differs from the traditional Siamese-net in two ways. First, we adopt a double-margin contrastive loss with a dynamic margin tuning strategy to train the network which leads to more robust performance. Second, we introduce in the mimic learning regularization to improve the generalization ability of the network by preventing it from overfitting to the training data. Catering for the network learning, we collect a large-scale dataset, namely GeoPair, which consists of 68k matching image pairs and 63k non-matching pairs. Experiments on several standard instance retrieval datasets demonstrate the effectiveness of our method. Deep convolutional neural networks comprise a subclass of deep neural networks (DNN) with a constrained architecture that leverages the spatial and temporal structure of the domain they model. Convolutional networks achieve the best predictive performance in areas such as speech and image recognition by hierarchically composing simple local features into complex models. Although DNNs have been used in drug discovery for QSAR and ligand-based bioactivity predictions, none of these models have benefited from this powerful convolutional architecture. This paper introduces AtomNet, the first structure-based, deep convolutional neural network designed to predict the bioactivity of small molecules for drug discovery applications. We demonstrate how to apply the convolutional concepts of feature locality and hierarchical composition to the modeling of bioactivity and chemical interactions. In further contrast to existing DNN techniques, we show that AtomNet’s application of local convolutional filters to structural target information successfully predicts new active molecules for targets with no previously known modulators. Finally, we show that AtomNet outperforms previous docking approaches on a diverse set of benchmarks by a large margin, achieving an AUC greater than 0.9 on 57.8 of the targets in the DUDE benchmark. 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.