English

Predicting Protein-Ligand Binding Affinity via Joint Global-Local Interaction Modeling

Biomolecules 2022-09-28 v1 Artificial Intelligence Machine Learning Molecular Networks

Abstract

The prediction of protein-ligand binding affinity is of great significance for discovering lead compounds in drug research. Facing this challenging task, most existing prediction methods rely on the topological and/or spatial structure of molecules and the local interactions while ignoring the multi-level inter-molecular interactions between proteins and ligands, which often lead to sub-optimal performance. To solve this issue, we propose a novel global-local interaction (GLI) framework to predict protein-ligand binding affinity. In particular, our GLI framework considers the inter-molecular interactions between proteins and ligands, which involve not only the high-energy short-range interactions between closed atoms but also the low-energy long-range interactions between non-bonded atoms. For each pair of protein and ligand, our GLI embeds the long-range interactions globally and aggregates local short-range interactions, respectively. Such a joint global-local interaction modeling strategy helps to improve prediction accuracy, and the whole framework is compatible with various neural network-based modules. Experiments demonstrate that our GLI framework outperforms state-of-the-art methods with simple neural network architectures and moderate computational costs.

Keywords

Cite

@article{arxiv.2209.13014,
  title  = {Predicting Protein-Ligand Binding Affinity via Joint Global-Local Interaction Modeling},
  author = {Yang Zhang and Gengmo Zhou and Zhewei Wei and Hongteng Xu},
  journal= {arXiv preprint arXiv:2209.13014},
  year   = {2022}
}
R2 v1 2026-06-28T02:09:04.896Z