{"about":{"site":"https://codewithpapers.app","non_affiliation":"Code with Papers and Syntology are not affiliated with, endorsed by, or sponsored by Papers with Code, Meta, or the pwc-archive mirror.","licence":"CC BY-SA 4.0","licence_url":"https://creativecommons.org/licenses/by-sa/4.0/legalcode","attribution":"https://codewithpapers.app/attribution","modified":"archive material modified by Syntology; see the attribution page"},"url":"/paper/aanet-virtual-screening-under-structural","title":"AANet: Virtual Screening under Structural Uncertainty via Alignment and Aggregation","arxiv_id":"2506.05768","date":"2025-06-06","proceeding":null,"authors":["Wenyu Zhu","Jianhui Wang","Bowen Gao","Yinjun Jia","Haichuan Tan","Ya-Qin Zhang","Wei-Ying Ma","Yanyan Lan"],"abstract":"Virtual screening (VS) is a critical component of modern drug discovery, yet most existing methods--whether physics-based or deep learning-based--are developed around holo protein structures with known ligand-bound pockets. Consequently, their performance degrades significantly on apo or predicted structures such as those from AlphaFold2, which are more representative of real-world early-stage drug discovery, where pocket information is often missing. In this paper, we introduce an alignment-and-aggregation framework to enable accurate virtual screening under structural uncertainty. Our method comprises two core components: (1) a tri-modal contrastive learning module that aligns representations of the ligand, the holo pocket, and cavities detected from structures, thereby enhancing robustness to pocket localization error; and (2) a cross-attention based adapter for dynamically aggregating candidate binding sites, enabling the model to learn from activity data even without precise pocket annotations. We evaluated our method on a newly curated benchmark of apo structures, where it significantly outperforms state-of-the-art methods in blind apo setting, improving the early enrichment factor (EF1%) from 11.75 to 37.19. Notably, it also maintains strong performance on holo structures. These results demonstrate the promise of our approach in advancing first-in-class drug discovery, particularly in scenarios lacking experimentally resolved protein-ligand complexes.","url_abs":"https://arxiv.org/abs/2506.05768v1","url_pdf":"https://arxiv.org/pdf/2506.05768v1.pdf","source":{"archive":"pwc-archive (Hugging Face), CC BY-SA 4.0","snapshot":"2025-07-28","licence_url":"https://creativecommons.org/licenses/by-sa/4.0/legalcode","row_kind":"abstracts"},"code_links":[],"tasks":[{"task_slug":"contrastive-learning","task_name":"Contrastive Learning"},{"task_slug":"drug-discovery","task_name":"Drug Discovery"}],"methods":[{"method_slug":"adapter","method_name":"Adapter"},{"method_slug":"contrastive-learning","method_name":"Contrastive Learning"}],"datasets_introduced":[],"methods_introduced":[],"results":[],"syntology":{"syntology_url":null,"atlas_url":"https://app.syntology.ai/?focus=2506.05768","mcp":{"get_harvested_code_for_paper":{"arxiv_id":"2506.05768"}},"developers":"https://syntology.ai/developers","read_at":"2026-09-24T18:15:14+00:00","read_at_is":"when the build read Syntology's graph, not when any sample ran","claim":"Per-sample execution status on synthesized fixtures; not a correctness claim about the paper. 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