A deep learning method for drug-target affinity prediction based on sequence interaction information mining

PeerJ. 2023 Dec 11:11:e16625. doi: 10.7717/peerj.16625. eCollection 2023.


Background: A critical aspect of in silico drug discovery involves the prediction of drug-target affinity (DTA). Conducting wet lab experiments to determine affinity is both expensive and time-consuming, making it necessary to find alternative approaches. In recent years, deep learning has emerged as a promising technique for DTA prediction, leveraging the substantial computational power of modern computers.

Methods: We proposed a novel sequence-based approach, named KC-DTA, for predicting drug-target affinity (DTA). In this approach, we converted the target sequence into two distinct matrices, while representing the molecule compound as a graph. The proposed method utilized k-mers analysis and Cartesian product calculation to capture the interactions and evolutionary information among various residues, enabling the creation of the two matrices for target sequence. For molecule, it was represented by constructing a molecular graph where atoms serve as nodes and chemical bonds serve as edges. Subsequently, the obtained target matrices and molecule graph were utilized as inputs for convolutional neural networks (CNNs) and graph neural networks (GNNs) to extract hidden features, which were further used for the prediction of binding affinity.

Results: In order to evaluate the effectiveness of the proposed method, we conducted several experiments and made a comprehensive comparison with the state-of-the-art approaches using multiple evaluation metrics. The results of our experiments demonstrated that the KC-DTA method achieves high performance in predicting drug-target affinity (DTA). The findings of this research underscore the significance of the KC-DTA method as a valuable tool in the field of in silico drug discovery, offering promising opportunities for accelerating the drug development process. All the data and code are available for access on https://github.com/syc2017/KCDTA.

Keywords: Convolutional neural network; Deep learning; Drug-target affinity prediction; Graph neural network; Protein sequence.

MeSH terms

  • Benchmarking
  • Biological Evolution
  • Deep Learning*
  • Drug Delivery Systems
  • Drug Discovery

Grants and funding

This work was supported by the National Natural Science Foundation of Shandong Province (No. ZR2022QF111). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.