Predicting Drug-Target Interaction Using a Novel Graph Neural Network with 3D Structure-Embedded Graph Representation

J Chem Inf Model. 2019 Sep 23;59(9):3981-3988. doi: 10.1021/acs.jcim.9b00387. Epub 2019 Sep 6.

Abstract

We propose a novel deep learning approach for predicting drug-target interaction using a graph neural network. We introduce a distance-aware graph attention algorithm to differentiate various types of intermolecular interactions. Furthermore, we extract the graph feature of intermolecular interactions directly from the 3D structural information on the protein-ligand binding pose. Thus, the model can learn key features for accurate predictions of drug-target interaction rather than just memorize certain patterns of ligand molecules. As a result, our model shows better performance than docking and other deep learning methods for both virtual screening (AUROC of 0.968 for the DUD-E test set) and pose prediction (AUROC of 0.935 for the PDBbind test set). In addition, it can reproduce the natural population distribution of active molecules and inactive molecules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Computational Biology / methods*
  • Computer Graphics*
  • Ligands
  • Models, Molecular
  • Molecular Targeted Therapy*
  • Neural Networks, Computer*
  • Protein Conformation
  • Proteins / chemistry
  • Proteins / metabolism

Substances

  • Ligands
  • Proteins