TC-DTA: Predicting Drug-Target Binding Affinity With Transformer and Convolutional Neural Networks

Abstract

Bioinformatics is a rapidly evolving field that applies computational methods to analyze and interpret biological data. A key task in bioinformatics is identifying novel drug-target interactions (DTIs), which plays a crucial role in drug discovery. Most computational approaches treat DTI prediction as a binary classification problem, determining whether drug-target pairs interact. However, with the growing availability of drug-target binding affinity data, this binary task can be reframed as a regression problem focused on drug-target affinity (DTA). DTA quantifies the strength of drug-target binding, offering more detailed insights than DTI and serving as a valuable tool for virtual screening in drug discovery. Accurately predicting compound interactions with targets can accelerate the drug development process. In this study, we introduce a deep learning model named TC-DTA for DTA prediction, leveraging convolutional neural networks (CNN) and the encoder module of the transformer architecture. We begin by extracting raw drug SMILES strings and protein amino acid sequences from the dataset, which are then represented using various encoding methods. Subsequently, we employ CNN and the transformer’s encoder module to extract features from the drug SMILES strings and protein sequences, respectively. Finally, the feature information is concatenated and input into a multi-layer perceptron to predict binding affinity scores. We evaluated our model on two benchmark DTA datasets, Davis and KIBA, comparing it with methods such as KronRLS, SimBoost, and DeepDTA. Our model, TC-DTA, outperformed these baseline methods based on evaluation metrics like Mean Squared Error (MSE), Concordance Index (CI), and Regression towards the Mean Index ( ${r}_{m}^{{2}}$ ). These results highlight the effectiveness of the Transformer’s encoder and CNN in extracting meaningful representations from sequences, thereby enhancing DTA prediction accuracy. This deep learning model can accelerate drug discovery by identifying drug candidates with high binding affinity to specific targets. Compared to traditional methods, machine learning technology offers a more effective and efficient approach to drug discovery.