Binding affinity prediction for protein-ligand complex using deep attention mechanism based on intermolecular interactions

BMC Bioinformatics. 2021 Nov 8;22(1):542. doi: 10.1186/s12859-021-04466-0.

Abstract

Background: Accurate prediction of protein-ligand binding affinity is important for lowering the overall cost of drug discovery in structure-based drug design. For accurate predictions, many classical scoring functions and machine learning-based methods have been developed. However, these techniques tend to have limitations, mainly resulting from a lack of sufficient energy terms to describe the complex interactions between proteins and ligands. Recent deep-learning techniques can potentially solve this problem. However, the search for more efficient and appropriate deep-learning architectures and methods to represent protein-ligand complex is ongoing.

Results: In this study, we proposed a deep-neural network model to improve the prediction accuracy of protein-ligand complex binding affinity. The proposed model has two important features, descriptor embeddings with information on the local structures of a protein-ligand complex and an attention mechanism to highlight important descriptors for binding affinity prediction. The proposed model performed better than existing binding affinity prediction models on most benchmark datasets.

Conclusions: We confirmed that an attention mechanism can capture the binding sites in a protein-ligand complex to improve prediction performance. Our code is available at https://github.com/Blue1993/BAPA .

Keywords: Attention mechanism; Binding affinity; Protein–ligand complex; Structure-based drug design.

MeSH terms

  • Binding Sites
  • Ligands
  • Machine Learning*
  • Protein Binding
  • Proteins* / metabolism

Substances

  • Ligands
  • Proteins