PLA-SGCN: Protein-Ligand Binding Affinity Prediction by Integrating Similar Pairs and Semi-supervised Graph Convolutional Network (2405.07452v2)

Abstract: The protein-ligand binding affinity (PLA) prediction goal is to predict whether or not the ligand could bind to a protein sequence. Recently, in PLA prediction, deep learning has received much attention. Two steps are involved in deep learning-based approaches: feature extraction and task prediction step. Many deep learning-based approaches concentrate on introducing new feature extraction networks or integrating auxiliary knowledge like protein-protein interaction networks or gene ontology knowledge. Then, a task prediction network is designed simply using some fully connected layers. This paper aims to integrate retrieved similar hard protein-ligand pairs in PLA prediction (i.e., task prediction step) using a semi-supervised graph convolutional network (GCN). Hard protein-ligand pairs are retrieved for each input query sample based on the manifold smoothness constraint. Then, a graph is learned automatically in which each node is a protein-ligand pair, and each edge represents the similarity between pairs. In other words, an end-to-end framework is proposed that simultaneously retrieves hard similar samples, learns protein-ligand descriptor, learns the graph topology of the input sample with retrieved similar hard samples (learn adjacency matrix), and learns a semi-supervised GCN to predict the binding affinity (as task predictor). The training step adjusts the parameter values, and in the inference step, the learned model is fine-tuned for each input sample. To evaluate the proposed approach, it is applied to the four well-known PDBbind, Davis, KIBA, and BindingDB datasets. The results show that the proposed method significantly performs better than the comparable approaches.