Enhancing Local Functional Structure Features to Improve Drug–Target Interaction Prediction
Year: 2025
Type: article
Abstract: Molecular simulation is central to modern drug discovery but is often limited by high computational cost and the complexity of molecular interactions. Deep-learning drug-target interaction (DTI) prediction can accelerate screening; however, many models underuse the local functional structure features-binding motifs, reactive groups, and residue-level fragments-that drive recognition. We present LoF-DTI, a framework that explicitly represents and couples such local features. Drugs are converted from SMILES into molecular graphs and targets from sequences into feature representations. On the drug side, a Jumping Knowledge (JK) enhanced Graph Isomorphism Network (GIN) extracts atom- and neighborhood-level patterns; on the target side, residual CNN blocks with progressively enlarged receptive fields, augmented by N-mer substructural statistics, capture multi-scale local motifs. A Gated Cross-Attention (GCA) module then performs atom-to-residue interaction learning, highlighting decisive local pairs and providing token-level interpretability through attention scores. By prioritizing locality during both encoding and interaction, LoF-DTI delivers competitive results across multiple benchmarks and improves early retrieval relevant to virtual screening. Case analyses show that the model recovers known functional binding sites, suggesting strong potential to provide mechanism-aware guidance for molecular simulation and to streamline the drug design pipeline.
Authors: Baoming Feng, Haofan Du, Henry H. Y. Tong, Xu Wang, Kefeng Li
Language: English
Subfield: Computational Theory and Mathematics
Field: Computer Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,499
OpenAlex ID: W4415350263