Enhanced inhibitor-kinase affinity prediction via integrated multimodal analysis of drug molecule and protein...

The accurate prediction of inhibitor-kinase binding affinity is pivotal for advancing drug development and precision medicine. In this study, we developed predictive models for human kinases, including cyclin-dependent kinases (CDKs), mitogen-activated protein kinases (MAP kinases), glycogen synthase kinases (GSKs), CDK-like kinases (CMGC kinase group) and receptor tyrosine kinases (RTKs)-key regulators of cellular signaling and disease progression. These kinases serve as primary drug targets in cancer and other critical diseases. To enhance affinity prediction precision, we introduce an innovative multimodal fusion model, KinNet. The model integrates the GraphKAN network, which effectively captures both local and global structural features of drug molecules. Furthermore, it leverages kernel functions and learnable activation functions to dynamically optimize node and edge feature representations. Additionally, the model incorporates the Conv-Enhanced Mamba module, combining Conv1D's ability to capture local features with Mamba's strength in processing long sequences, facilitating comprehensive feature extraction from protein sequences and molecular fingerprints. Experimental results confirm that the KinNet model achieves superior prediction accuracy compared to existing approaches, underscoring its potential to elucidate inhibitor-kinase binding mechanisms. This model serves as a robust computational framework to support drug discovery and the development of kinase-targeted therapies.