E2EATP: Fast and High-Accuracy Protein–ATP Binding Residue Prediction via Protein Language Model Embedding

Identifying the ATP-binding sites of proteins is fundamentally important to uncover the mechanisms of protein functions and explore drug discovery. Many computational methods are proposed to predict ATP-binding sites. However, due to the limitation of the quality of feature representation, the prediction performance still has a big room for improvement. In this study, we propose an end-to-end deep learning model, E2EATP, to dig out more discriminative information from a protein sequence for improving the ATP-binding site prediction performance. Concretely, we employ a pretrained deep learning-based protein language model (ESM2) to automatically extract high-latent discriminative representations of protein sequences relevant for protein functions. Based on ESM2, we design a residual convolutional neural network to train a protein–ATP binding site prediction model. Furthermore, a weighted focal loss function is used to reduce the negative impact of imbalanced data on the model training stage. Experimental results on the two independent testing data sets demonstrate that E2EATP could achieve higher Matthew’s correlation coefficient and AUC values than most existing state-of-the-art prediction methods. The speed (about 0.05 s per protein) of E2EATP is much faster than the other existing prediction methods. Detailed data analyses show that the major advantage of E2EATP lies at the utilization of the pretrained protein language model that extracts more discriminative information from the protein sequence only. The standalone package of E2EATP is freely available for academic at https://github.com/jun-csbio/e2eatp/.