Abstract <p>The discovery and development of novel pharmaceutical agents is characterized by high costs, lengthy timelines, and significant safety concerns. Traditional drug discovery involves pharmacologists manually screening drug molecules against protein targets, focusing on binding within protein cavities. However, this manual process is slow and inherently limited. Given these constraints, the use of deep learning techniques to predict drug-target interaction (DTI) affinities is both significant and promising for future applications. This paper introduces an innovative deep learning architecture designed to enhance the prediction of DTI affinities. The model ingeniously combines graph neural networks, pre-trained large-scale protein models, and attention mechanisms to improve performance. In this framework, molecular structures are represented as graphs and processed through graph neural networks and multiscale convolutional networks to facilitate feature extraction. Simultaneously, protein sequences are encoded using pre-trained ESM-2 large models and processed with bidirectional long short-term memory networks. Subsequently, the molecular and protein embeddings derived from these processes are integrated within a fusion module to compute affinity scores. Experimental results demonstrate that our proposed model outperforms existing methods on two publicly available datasets.</p> Graphical Abstract <p></p>