Copy-Augmented Representation for Structure Invariant Template-Free Retrosynthesis

• URL: http://arxiv.org/abs/2510.16588v1
• Date: Sat, 18 Oct 2025 17:25:36 GMT
• Title: Copy-Augmented Representation for Structure Invariant Template-Free Retrosynthesis
• Authors: Jiaxi Zhuang, Yu Zhang, Aimin Zhou, Ying Qian,
• Abstract summary: C-SMILES is a novel representation that decomposes traditional SMILES into element-token pairs with five special tokens.<n>Our approach integrates SMILES alignment guidance to enhance attention consistency and ground-truth atom mapping.<n>This work establishes a new paradigm for structure-aware molecular generation with 99.9% validity in generated molecules.
• Score: 17.5286075847689
• License: http://arxiv.org/licenses/nonexclusive-distrib/1.0/
• 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.

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