DSC-bsite: a dynamic-static collaborative multimodal graph learning method for protein-small molecule binding site...

Accurate identification of protein-small molecule binding sites is a fundamental problem in computational biology and drug discovery. Existing sequence-based methods lack explicit spatial awareness, while structure-based approaches often struggle to integrate long-range functional dependencies and semantic information, leading to limited generalization on low-similarity or sparsely annotated proteins. To address these challenges, we propose DSC-BSite, a dynamic-static collaborative multimodal graph learning framework for residue-level binding site prediction. First, a Static Global Sequence Encoding module captures multi-scale local patterns and long-range contextual dependencies from protein sequences. Second, a Gated Dual-Graph Dynamic Propagation (GDDP) module jointly models spatial geometric interactions and sequence-derived functional correlations using a dynamic spatial graph and an attention-guided sequence graph, enabling adaptive residue interaction modeling. Third, a PPI-guided Structural-Semantic Alignment (PSSA) pre-training strategy aligns structural representations with function-aware semantic embeddings, enhancing the biological expressiveness of structural features without requiring PPI information during inference. Experimental results on the UniProtSMB and SJC benchmark datasets demonstrate that DSC-BSite achieves competitive performance across multiple evaluation metrics, with particularly strong results in Recall on UniProtSMB and Precision and MCC on SJC.