DeepPhosPPI: a deep learning framework with attention-CNN and transformer for predicting phosphorylation effects on protein–protein interactions

Protein phosphorylation regulates protein function and cellular signaling pathways, and is strongly associated with diseases, including neurodegenerative disorders and cancer. Phosphorylation plays a critical role in regulating protein activity and cellular signaling by modulating protein–protein interactions (PPIs). It alters binding affinities and interaction networks, thereby influencing biological processes and maintaining cellular homeostasis. Experimental validation of these effects is labor-intensive and expensive, highlighting the need for efficient computational approaches. We propose DeepPhosPPI, the first sequence-based deep learning framework for phosphorylation effects on PPIs prediction, which employs the pre-trained protein language model for feature embedding, with ProtBERT and ESM-2 as alternative backbone encoders. By combining attention-based convolutional neural network and Transformer models, DeepPhosPPI accurately predicts phosphorylation effects. The experimental results show that DeepPhosPPI consistently outperforms state-of-the-art methods in multiple tasks, including functional sites identification and regulatory effect classification.