Jing Lan

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.