{"ID":2853468,"CreatedAt":"2026-06-01T04:54:23.091178241Z","UpdatedAt":"2026-06-01T04:54:23.091178241Z","DeletedAt":null,"paper_url":"https://arxiv.org/abs/2510.16588","arxiv_id":"2510.16588","title":"Copy-Augmented Representation for Structure Invariant Template-Free Retrosynthesis","abstract":"Retrosynthesis prediction is fundamental to drug discovery and chemical synthesis, requiring the identification of reactants that can produce a target molecule. Current template-free methods struggle to capture the structural invariance inherent in chemical reactions, where substantial molecular scaffolds remain unchanged, leading to unnecessarily large search spaces and reduced prediction accuracy. We introduce C-SMILES, a novel molecular representation that decomposes traditional SMILES into element-token pairs with five special tokens, effectively minimizing editing distance between reactants and products. Building upon this representation, we incorporate a copy-augmented mechanism that dynamically determines whether to generate new tokens or preserve unchanged molecular fragments from the product. Our approach integrates SMILES alignment guidance to enhance attention consistency with ground-truth atom mappings, enabling more chemically coherent predictions. Comprehensive evaluation on USPTO-50K and large-scale USPTO-FULL datasets demonstrates significant improvements: 67.2% top-1 accuracy on USPTO-50K and 50.8% on USPTO-FULL, with 99.9% validity in generated molecules. This work establishes a new paradigm for structure-aware molecular generation with direct applications in computational drug discovery.","short_abstract":"Retrosynthesis prediction is fundamental to drug discovery and chemical synthesis, requiring the identification of reactants that can produce a target molecule. Current template-free methods struggle to capture the structural invariance inherent in chemical reactions, where substantial molecular scaffolds remain unchan...","url_abs":"https://arxiv.org/abs/2510.16588","url_pdf":"https://arxiv.org/pdf/2510.16588v1","authors":"[\"Jiaxi Zhuang\",\"Yu Zhang\",\"Aimin Zhou\",\"Ying Qian\"]","published":"2025-10-18T17:25:36Z","proceeding":"cs.LG","tasks":"[\"cs.LG\",\"cs.CL\"]","methods":"[]","has_code":false}