Improving structure-based protein-ligand affinity prediction by graph representation learning and ensemble learning

Abstract

Predicting protein-ligand binding affinity presents a viable solution for accelerating the discovery of new lead compounds. The recent widespread application of machine learning approaches, especially graph neural networks, has brought new advancements in this field. However, some existing structure-based methods treat protein macromolecules and ligand small molecules in the same way and ignore the data heterogeneity, potentially leading to incomplete exploration of the biochemical information of ligands. In this work, we propose LGN, a graph neural network-based fusion model with extra ligand feature extraction to effectively capture local features and global features within the protein-ligand complex, and make use of interaction fingerprints. By combining the ligand-based features and interaction fingerprints, LGN achieves Pearson correlation coefficients of up to 0.842 on the PDBbind 2016 core set, compared to 0.807 when using the features of complex graphs alone. Finally, we verify the rationalization and generalization of our model through comprehensive experiments. We also compare our model with state-of-the-art baseline methods, which validates the superiority of our model. To reduce the impact of data similarity, we increase the robustness of the model by incorporating ensemble learning.