The paper introduces ReGeoDTA, a framework that preserves chemical heterogeneity and continuous geometric relationships in drug and protein representations to improve drug–target affinity prediction. Experiments on three benchmark datasets show that maintaining representation fidelity consistently enhances predictive accuracy across various DTA architectures, while degrading representations harms performance and cannot be recovered by more complex downstream models. The study highlights representation fidelity as a key upstream design principle for accurate and generalizable affinity prediction.
By Yixiao Li, Yining Qian, Yefan Chen, Zenghui Chen, Jiayue Sun, Yuhai Zhao, Cheng Tan, An-Yang Lu
arXiv:2506. 14488v2 Announce Type: replace-cross Abstract: Structure-based drug design (SBDD) models are central to modern pharmaceutical research, enabling the rational exploration of protein-ligand interactions at atomic resolution.
By Dong Xu, Zhangfan Yang, Junchuang Cai, Sisi Yuan, Zexuan Zhu, Jianqiang Li, Junkai Ji
arXiv:2607. 20550v1 Announce Type: cross Abstract: The traditional "one drug, one target" paradigm of structure-based drug design (SBDD) frequently proves inadequate for treating multifactorial diseases such as cancer and neurodegenerative disorders, owing to compensatory signaling pathways and the emergence of drug resistance.
By Tianming Han, Zhijie Pan, Wenchi Ge, Qi Zhao
arXiv:2607. 19237v1 Announce Type: new Abstract: Designing small molecule ligands that bind with high affinity to specific protein pockets is a fundamental goal in drug discovery, as small molecules constitute a major fraction of approved therapeutics.
By Yiming Qin, Kai Yi, Miruna Cretu, Sjors H. W. Scheres, Pietro Li\`o, Pascal Frossard
arXiv:2606. 05198v1 Announce Type: cross Abstract: Nucleic acids are increasingly recognized as therapeutic targets beyond conventional protein-centered drug discovery, yet accurate and efficient docking of small molecules to nucleic acid structures remains challenging.
By Shi Li (College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, P. R. China), Xujun Zhang (College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, P. R. China), Mingquan Liu (Faculty of Health Sciences, University of Macau, Macau SAR, China), Hui Zhang (College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, P. R. China, Shanghai Innovation Institute, Shanghai, China), Shuoying Jia (College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, P. R. China, Shanghai Innovation Institute, Shanghai, China), Yu Kang (College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, P. R. China, Shanghai Innovation Institute, Shanghai, China), Tingjun Hou (College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, P. R. China, Zhejiang Provincial Key Laboratory for Intelligent Drug Discovery and Development, Jinhua Institute of Zhejiang University, Zhejiang, China), Peichen Pan (College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, P. R. China, Zhejiang Provincial Key Laboratory for Intelligent Drug Discovery and Development, Jinhua Institute of Zhejiang University, Zhejiang, China)