LAUSR

Summary Computational approaches for understanding compound-protein interactions (CPIs) can greatly facilitate drug development. Recently, a number of deep-learning-based methods have been proposed to predict binding affinities and attempt to capture local interaction sites in compounds and proteins through neural attentions (i.e., neural network architectures that enable the interpretation of feature importance). Here, we compiled a benchmark dataset containing the inter-molecular non-covalent interactions for more than 10,000 compound-protein pairs and systematically evaluated the interpretability of neural attentions in existing models. We also developed a multi-objective neural network, called MONN, to predict both non-covalent interactions and binding affinities between compounds and proteins. Comprehensive evaluation demonstrated that MONN can successfully predict the non-covalent interactions between compounds and proteins that cannot be effectively captured by neural attentions in previous prediction methods. Moreover, MONN outperforms other state-of-the-art methods in predicting binding affinities. Source code for MONN is freely available for download at https://github.com/lishuya17/MONN .