Structure-inclusive similarity based directed GNN: a method that can control information flow to predict drug–target binding affinity

Abstract Motivation Exploring the association between drugs and targets is essential for drug discovery and repurposing. Comparing with the traditional methods that regard the exploration as a binary classification task, predicting the drug–target binding affinity can provide more specific information. Many studies work based on the assumption that similar drugs may interact with the same target. These methods constructed a symmetric graph according to the undirected drug similarity or target similarity. Although these similarities can measure the difference between two molecules, it is unable to analyze the inclusion relationship of their substructure. For example, if drug A contains all the substructures of drug B, then in the message-passing mechanism of the graph neural network, drug A should acquire all the properties of drug B, while drug B should only obtain some of the properties of A. Results To this end, we proposed a structure-inclusive similarity (SIS) which measures the similarity of two drugs by considering the inclusion relationship of their substructures. Based on SIS, we constructed a drug graph and a target graph, respectively, and predicted the binding affinities between drugs and targets by a graph convolutional network-based model. Experimental results show that considering the inclusion relationship of the substructure of two molecules can effectively improve the accuracy of the prediction model. The performance of our SIS-based prediction method outperforms several state-of-the-art methods for drug–target binding affinity prediction. The case studies demonstrate that our model is a practical tool to predict the binding affinity between drugs and targets. Availability and implementation Source codes and data are available at https://github.com/HuangStomach/SISDTA.