CoGANPPIS: Coevolution-enhanced Global Attention Neural Network for Protein-Protein Interaction Site Prediction

Protein-protein interactions are essential in biochemical processes. Accurate prediction of the protein-protein interaction sites (PPIs) deepens our understanding of biological mechanism and is crucial for new drug design. However, conventional experimental methods for PPIs prediction are costly and time-consuming so that many computational approaches, especially ML-based methods, have been developed recently. Although these approaches have achieved gratifying results, there are still two limitations: (1) Most models have excavated some useful input features, but failed to take coevolutionary features into account, which could provide clues for inter-residue relationships; (2) The attention-based models only allocate attention weights for neighboring residues, instead of doing it globally, neglecting that some residues being far away from the target residues might also matter. We propose a coevolution-enhanced global attention neural network, a sequence-based deep learning model for PPIs prediction, called CoGANPPIS. It utilizes three layers in parallel for feature extraction: (1) Local-level representation aggregation layer, which aggregates the neighboring residues' features; (2) Global-level representation learning layer, which employs a novel coevolution-enhanced global attention mechanism to allocate attention weights to all the residues on the same protein sequences; (3) Coevolutionary information learning layer, which applies CNN & pooling to coevolutionary information to obtain the coevolutionary profile representation. Then, the three outputs are concatenated and passed into several fully connected layers for the final prediction. Application on two benchmark datasets demonstrated a state-of-the-art performance of our model. The source code is publicly available at https://github.com/Slam1423/CoGANPPIS_source_code.