Hexiao Ding

Jing Lan, Hexiao Ding, Hongzhao Chen et al.

AI models for drug discovery and chemical literature mining must interpret molecular images and generate outputs consistent with 3D geometry and stereochemistry. Most molecular language models rely on strings or graphs, while vision-language models often miss stereochemical details and struggle to map continuous 3D structures into discrete tokens. We propose DeepMoLM: Deep Molecular Language M odeling, a dual-view framework that grounds high-resolution molecular images in geometric invariants derived from molecular conformations. DeepMoLM preserves high-frequency evidence from 1024 $\times$ 1024 inputs, encodes conformer neighborhoods as discrete Extended 3-Dimensional Fingerprints, and fuses visual and geometric streams with cross-attention, enabling physically grounded generation without atom coordinates. DeepMoLM improves PubChem captioning with a 12.3% relative METEOR gain over the strongest generalist baseline while staying competitive with specialist methods. It produces valid numeric outputs for all property queries and attains MAE 13.64 g/mol on Molecular Weight and 37.89 on Complexity in the specialist setting. On ChEBI-20 description generation from images, it exceeds generalist baselines and matches state-of-the-art vision-language models. Code is available at https://github.com/1anj/DeepMoLM.

Hongzhao Chen, Hexiao Ding, Yufeng Jiang et al.

Reliable and interpretable tumor classification from clinical imaging remains a core challenge. The main difficulties arise from heterogeneous modality quality, limited annotations, and the absence of structured anatomical guidance. We present REACT-KD, a Region-Aware Cross-modal Topological Knowledge Distillation framework that transfers supervision from high-fidelity multi-modal sources into a lightweight CT-based student model. The framework employs a dual teacher design. One branch captures structure-function relationships through dual-tracer PET/CT, while the other models dose-aware features using synthetically degraded low-dose CT. These branches jointly guide the student model through two complementary objectives. The first achieves semantic alignment through logits distillation, and the second models anatomical topology through region graph distillation. A shared CBAM3D module ensures consistent attention across modalities. To improve reliability in deployment, REACT-KD introduces modality dropout during training, which enables robust inference under partial or noisy inputs. As a case study, we applied REACT-KD to hepatocellular carcinoma staging. The framework achieved an average AUC of 93.5\% on an internal PET/CT cohort and maintained 76.6\% to 81.5\% AUC across varying levels of dose degradation in external CT testing. Decision curve analysis further shows that REACT-KD consistently provides the highest net clinical benefit across all thresholds, confirming its value in real-world diagnostic practice. Code is available at: https://github.com/Kinetics-JOJO/REACT-KD

Jing Lan, Hexiao Ding, Hongzhao Chen et al.

Accurate identification of drug-target interactions (DTI) remains a central challenge in computational pharmacology, where sequence-based methods offer scalability. This work introduces a sequence-based drug-target interaction framework that integrates structural priors into protein representations while maintaining high-throughput screening capability. Evaluated across multiple benchmarks, the model achieves state-of-the-art performance on Human and BioSNAP datasets and remains competitive on BindingDB. In virtual screening tasks, it surpasses prior methods on LIT-PCBA, yielding substantial gains in AUROC and BEDROC. Ablation studies confirm the critical role of learned aggregation, bilinear attention, and contrastive alignment in enhancing predictive robustness. Embedding visualizations reveal improved spatial correspondence with known binding pockets and highlight interpretable attention patterns over ligand-residue contacts. These results validate the framework's utility for scalable and structure-aware DTI prediction.

Jing Lan, Hexiao Ding, Hongzhao Chen et al.

Accurate prediction of protein-ligand interactions is essential for computer-aided drug discovery. However, existing methods often fail to capture solvent-dependent conformational changes and lack the ability to jointly learn multiple related tasks. To address these limitations, we introduce a pre-training method that incorporates ligand conformational ensembles generated under diverse solvent conditions as augmented input. This design enables the model to learn both structural flexibility and environmental context in a unified manner. The training process integrates molecular reconstruction to capture local geometry, interatomic distance prediction to model spatial relationships, and contrastive learning to build solvent-invariant molecular representations. Together, these components lead to significant improvements, including a 3.7% gain in binding affinity prediction, an 82% success rate on the PoseBusters Astex docking benchmarks, and an area under the curve of 97.1% in virtual screening. The framework supports solvent-aware, multi-task modeling and produces consistent results across benchmarks. A case study further demonstrates sub-angstrom docking accuracy with a root-mean-square deviation of 0.157 angstroms, offering atomic-level insight into binding mechanisms and advancing structure-based drug design.