Ligand binding affinity prediction with fusion of graph neural networks and 3D structure-based complex graph

Abstract

Accurate prediction of protein–ligand binding affinity is pivotal for drug design and discovery. Here, we proposed a novel deep fusion graph neural networks framework named FGNN to learn the protein–ligand interactions from the 3D structures of protein–ligand complexes. Unlike 1D sequences for proteins or 2D graphs for ligands, the 3D graph of protein–ligand complex enables the more accurate representations of the protein–ligand interactions. Benchmark studies have shown that our fusion models FGNN can achieve more accurate prediction of binding affinity than any individual algorithm. The advantages of fusion strategies have been demonstrated in terms of expressive power of data, learning efficiency and model interpretability. Our fusion models show satisfactory performances on diverse data sets, demonstrating their generalization ability. Given the good performances in both binding affinity prediction and virtual screening, our fusion models are expected to be practically applied for drug screening and design. Our work highlights the potential of the fusion graph neural network algorithm in solving complex prediction problems in computational biology and chemistry. The fusion graph neural networks (FGNN) model is freely available in https://github.com/LinaDongXMU/FGNN.