Predicting drug–protein interaction using quasi-visual question answering system
File version
Accepted Manuscript (AM)
Author(s)
Li, Y
Chen, S
Xu, J
Yang, Y
Griffith University Author(s)
Primary Supervisor
Other Supervisors
Editor(s)
Date
Size
File type(s)
Location
License
Abstract
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.
Journal Title
Nature Machine Intelligence
Conference Title
Book Title
Edition
Volume
2
Issue
2
Thesis Type
Degree Program
School
Publisher link
Patent number
Funder(s)
Grant identifier(s)
Rights Statement
Rights Statement
© 2020 Nature Publishing Group. This is the author-manuscript version of this paper. Reproduced in accordance with the copyright policy of the publisher. Please refer to the journal website for access to the definitive, published version.
Item Access Status
Note
Access the data
Related item(s)
Subject
Pharmacology and pharmaceutical sciences
Persistent link to this record
Citation
Zheng, S; Li, Y; Chen, S; Xu, J; Yang, Y, Predicting drug–protein interaction using quasi-visual question answering system, Nature Machine Intelligence, 2020, 2 (2), pp. 134-140