Zhaohan Meng

Zhaohan Meng, Zhen Bai, Ke Yuan et al.

Protein-ligand modeling underpins computational drug discovery and molecular design. Existing protein-ligand benchmarks typically evaluate whether a protein and ligand interact and how strongly they bind, through tasks such as binary binding prediction and affinity regression. However, these evaluations provide limited evidence of whether models can localize binding sites or identify the non-covalent interactions underlying molecular recognition. To address this gap, we introduce InteractBind, a large-scale protein-ligand dataset comprising approximately 100k protein-ligand pairs, together with a benchmark for fine-grained evaluation. The core fine-grained task is that of binding-site localization, which uses protein-residue and ligand-atom interaction maps spanning six major types of non-covalent interactions to assess whether model-derived interaction maps localize binding sites. InteractBind further includes binding affinity and protein similarity-controlled splits to support realistic generalization assessment. Using InteractBind, we evaluate eight existing sequence-based and interaction-aware models, assessing binary binding prediction and binding-site localization. Results reveal limited binding-site localization despite strong binary binding prediction, with marked variation across non-covalent interaction types. Overall, InteractBind establishes a benchmark paradigm that encourages the development of more interpretable and physically grounded protein-ligand models.

Zhaohan Meng, Zaiqiao Meng, Siwei Liu et al.

Large Language Models (LLMs) have shown strong performance on static medical Question Answering (QA) tasks, yet their reasoning often deteriorates in multi-turn clinical dialogues where patient information is scattered across turns. This paper introduces TriMediQ, a triplet-structured approach that enhances the reasoning reliability of LLMs through explicit knowledge integration. TriMediQ first employs a frozen triplet extraction LLM to convert patient responses into clinically grounded triplets, ensuring factual precision via constrained prompting. These triplets are incorporated into a patient-specific Knowledge Graph (KG), from which a trainable projection module consisting of a graph encoder and a projector captures relational dependencies while keeping all LLM parameters frozen. During inference, the projection module guides multi-hop reasoning over the KG, enabling coherent clinical dialogue understanding. Experiments on two interactive medical QA benchmarks show that TriMediQ achieves up to 10.4\% improvement in accuracy over five existing baselines on the iMedQA dataset. These results demonstrate that structuring patient information as triplets can effectively improve the reasoning capability of LLMs in multi-turn medical QA.

Zhaohan Meng, Zaiqiao Meng, Ke Yuan et al.

Predicting drug-target interaction (DTI) is critical in the drug discovery process. Despite remarkable advances in recent DTI models through the integration of representations from diverse drug and target encoders, such models often struggle to capture the fine-grained interactions between drugs and protein, i.e. the binding of specific drug atoms (or substructures) and key amino acids of proteins, which is crucial for understanding the binding mechanisms and optimising drug design. To address this issue, this paper introduces a novel model, called FusionDTI, which uses a token-level Fusion module to effectively learn fine-grained information for Drug-Target Interaction. In particular, our FusionDTI model uses the SELFIES representation of drugs to mitigate sequence fragment invalidation and incorporates the structure-aware (SA) vocabulary of target proteins to address the limitation of amino acid sequences in structural information, additionally leveraging pre-trained language models extensively trained on large-scale biomedical datasets as encoders to capture the complex information of drugs and targets. Experiments on three well-known benchmark datasets show that our proposed FusionDTI model achieves the best performance in DTI prediction compared with seven existing state-of-the-art baselines. Furthermore, our case study indicates that FusionDTI could highlight the potential binding sites, enhancing the explainability of the DTI prediction.