Improving protein-protein interaction site prediction using deep residual neural network

Abstract

Accurate identification of protein-protein interaction (PPI) sites is significantly important for understanding the mechanism of life and developing new drugs. However, it is expensive and time-consuming to identify PPI sites using wet-lab experiments. Developing computational methods is a new road to identify PPI sites, which can accelerate the procedure of PPI-related research. In this study, we propose a novel deep learning-based method (called D-PPIsite) to improve the accuracy of sequence-based PPI site prediction. In D-PPIsite, four discriminative sequence-driven features, i.e., position specific scoring matrix, relative solvent accessibility, position information and physical properties, are employed to feed into a well-designed deep learning module, consisting of convolutional, squeeze and excitation, and fully connected layers, to learn a prediction model. To reduce the risk of a single prediction model getting stuck in local optima, multiple prediction models with different initialization parameters are selected and integrated into one final model using the mean ensemble strategy. Experimental results on five independent testing data sets demonstrate that the proposed D-PPIsite can achieve an average accuracy of 80.2% and precision of 36.9%, covering 53.5% of all PPI sites while achieving the average Matthews correlation coefficient value (0.330) that is significantly higher than most of existing state-of-the-art prediction methods. We implement a new standalone-version predictor for predicting PPI sites, which is freely available at https://github.com/MingDongup/D-PPIsite for academic use.