Predicting the types and affinities of protein-protein interactions (PPIs) is crucial for understanding biological processes and developing novel therapeutic approaches. While encoding proteins themselves is essential, PPI networks can also provide rich prior knowledge for these predictive tasks. However, existing methods oversimplify the problem of PPI prediction in a semi-supervised manner when utilizing PPI networks, limiting their practical application. Furthermore, how to effectively use the rich prior knowledge of PPI networks for novel proteins not present in the network remains an unexplored issue. Additionally, due to inflexible architectures, most of existing methods cannot handle complexes containing an flexible number of proteins. To overcome these limitations, we introduce LLaPA (Large Language and Protein Assistant), a multimodal large language model that integrates proteins and PPI networks. LLaPA offers a more rational approach to utilizing PPI networks for PPI prediction and can fully exploit the information of PPI networks for unseen proteins. Through natural language instructions, LLaPA can accept flexible number of protein sequences and has the potential to perform various protein tasks. Experiments show that LLaPA achieves state-of-the-art performance in multi-label PPI (mPPI) type prediction and is capable of predicting the binding affinity between multiple interacting proteins based on sequence data.

Drug repurposing plays a critical role in accelerating treatment discovery, especially for complex and rare diseases. Biomedical knowledge graphs (KGs), which encode rich clinical associations, have been widely adopted to support this task. However, existing methods largely overlook common-sense biomedical concept knowledge in real-world labs, such as mechanistic priors indicating that certain drugs are fundamentally incompatible with specific treatments. To address this gap, we propose LLaDR, a Large Language Model-assisted framework for Drug Repurposing, which improves the representation of biomedical concepts within KGs. Specifically, we extract semantically enriched treatment-related textual representations of biomedical entities from large language models (LLMs) and use them to fine-tune knowledge graph embedding (KGE) models. By injecting treatment-relevant knowledge into KGE, LLaDR largely improves the representation of biomedical concepts, enhancing semantic understanding of under-studied or complex indications. Experiments based on benchmarks demonstrate that LLaDR achieves state-of-the-art performance across different scenarios, with case studies on Alzheimer’s disease further confirming its robustness and effectiveness.