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Predicting drug–protein interaction using quasi-visual question answering system

A Publisher Correction to this article was published on 11 August 2020

This article has been updated


Identifying novel drug–protein interactions is crucial for drug discovery. For this purpose, many machine learning-based methods have been developed based on drug descriptors and one-dimensional protein sequences. However, protein sequences cannot accurately reflect the interactions in three-dimensional space. However, direct input of three-dimensional structure is of low efficiency due to the sparse three-dimensional matrix, and is also prevented by the limited number of co-crystal structures available for training. Here we propose an end-to-end deep learning framework to predict the interactions by representing proteins with a two-dimensional distance map from monomer structures (Image) and drugs with molecular linear notation (String), following the visual question answering mode. For efficient training of the system, we introduce a dynamic attentive convolutional neural network to learn fixed-size representations from the variable-length distance maps and a self-attentional sequential model to automatically extract semantic features from the linear notations. Extensive experiments demonstrate that our model obtains competitive performance against state-of-the-art baselines on the directory of useful decoys, enhanced (DUD-E), human and BindingDB benchmark datasets. Further attention visualization provides biological interpretation to depict highlighted regions of both protein and drug molecules.

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Fig. 1: The framework of the proposed DrugVQA model.
Fig. 2: Performance comparisons of our proposed method and baselines on seen and unseen protein targets from the BindingDB dataset.
Fig. 3: Importance visualization of pocket and ligand pairs.

Data availability

All data used in this paper are publicly available and can be accessed at for the DUD-E dataset, for the BindingDB-IBM dataset, for human dataset and for the protein crystal structure.

Code availability

Demo, instructions and code for DrugVQA are available at

Change history


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The work was supported in part by the National Key R&D Program of China (2018YFC0910500), GD Frontier and Key Tech Innovation Program (2018B010109006,2019B020228001), the National Natural Science Foundation of China (61772566, U1611261 and 81801132, 81903540) and the programme for Guangdong Introducing Innovative and Entrepreneurial Teams (2016ZT06D211).

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Authors and Affiliations



S.Z., Y.L. and Y.Y. contributed concept and implementation. S.Z. and Y.L. co-designed experiments. S.Z. and Y.L. were responsible for programming. All authors contributed to the interpretation of results. S.Z. and Y.Y. wrote the manuscript. All authors reviewed and approved the final manuscript.

Corresponding authors

Correspondence to Jun Xu or Yuedong Yang.

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The authors declare no competing interests

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Supplementary information


Supplementary dataset details, neural network training and performance details, visualization details, Supplementary Figs. 1–5 and Table 1.

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Zheng, S., Li, Y., Chen, S. et al. Predicting drug–protein interaction using quasi-visual question answering system. Nat Mach Intell 2, 134–140 (2020).

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