Predicting nucleic acid binding sites by attention map-guided graph convolutional network with protein language embeddings and physicochemical information.

Abstract

Protein-nucleic acid binding sites play a crucial role in biological processes such as gene expression, signal transduction, replication, and transcription. In recent years, with the development of artificial intelligence, protein language models, graph neural networks, and transformer architectures have been adopted to develop both structure-based and sequence-based predictive models. Structure-based methods benefit from the spatial relationship between residues and have shown promising performance. However, structure-based information requires 3D protein structures, which is a challenge for large-scale protein sequence spaces. To address this limitation, researchers have attempted to use predicted protein structure information to guide binding site prediction. While this strategy has improved accuracy, it still depends on the quality of structure predictions. Thus, some studies have returned to prediction methods based solely on protein sequences, particularly those using protein language models, which have greatly enhanced the prediction accuracy. This paper proposes a novel protein-nucleic acid binding site prediction framework, ATtention Maps and Graph convolutional neural networks to predict nucleic acid-protein Binding sites (ATMGBs), which first fuses protein language embeddings with physicochemical properties to obtain multiview information, then leverages the attention map of a protein language model to simulate the relationship between residues, and then utilizes graph convolutional networks for enhancing the feature representations for final prediction. ATMGBs was evaluated on several different independent test sets. The results indicate that the proposed approach significantly improves sequence-based prediction performance, even achieving prediction accuracy comparable to structure-based frameworks. The dataset and code used in this study are available at https://github.com/lixiangli01/ATMGBs.