用大模型与专家反馈结合,自动发现复杂分子合成路径。
DeepRetro: Retrosynthetic Pathway Discovery using Iterative LLM Reasoning
- 融合大模型生成与模板精确性,通过迭代优化路径。
- 成功规划出传统方法难以处理的复杂天然产物合成路线。
- 适合药物研发和材料设计领域研究者使用。
复杂天然产物的合成仍是有机化学的重大挑战。我们提出DeepRetro,一种新型开源框架,通过将大语言模型(LLMs)、传统逆合成引擎与专家人类反馈紧密结合,在迭代设计循环中实现可行合成路径的发现。现有方法依赖纯模板或无约束的LLM输出,而DeepRetro结合模板的精准性与大模型的生成灵活性,通过严格的化学有效性验证和递归优化进行控制。该混合系统在算法检查与专家反馈引导下动态探索并修正合成路径。尽管在标准逆合成基准上表现优异,其真正优势在于为高复杂度天然产物提出新颖且可行的合成路线——这些目标曾长期无法被自动化方法攻克。通过案例研究,展示了该方法如何推动全合成新路径的建立,并促进人机协作。此外,DeepRetro为科学发现中如何应用大模型提供了可复现范例。我们公开了系统设计、算法及人机反馈流程,支持跨领域推广。通过开源释放,旨在赋能化学家应对日益复杂的合成目标,加速药物研发与材料设计进程。
原文摘要 · Abstract (English)
The synthesis of complex natural products remains one of the grand challenges of organic chemistry. We present DeepRetro, a major advancement in computational retrosynthesis that enables the discovery of viable synthetic routes for complex molecules typically considered beyond the reach of existing retrosynthetic methods. DeepRetro is a novel, open-source framework that tightly integrates large language models (LLMs), traditional retrosynthetic engines, and expert human feedback in an iterative design loop. Prior approaches rely solely on template-based methods or unconstrained LLM outputs. In contrast, DeepRetro combines the precision of template-based methods with the generative flexibility of LLMs, controlled by rigorous chemical validity checks and enhanced by recursive refinement. This hybrid system dynamically explores and revises synthetic pathways, guided by both algorithmic checks and expert chemist feedback through an interactive user interface. While DeepRetro achieves strong performance on standard retrosynthesis benchmarks, its true strength lies in its ability to propose novel, viable pathways to highly complex natural products-targets that have historically eluded automated planning. Through detailed case studies, we illustrate how this approach enables new routes for total synthesis and facilitates human-machine collaboration in organic chemistry. Beyond retrosynthesis, DeepRetro represents a working model for how to leverage LLMs in scientific discovery. We provide a transparent account of the system's design, algorithms, and human-feedback loop, enabling broad adaptation across scientific domains. By releasing DeepRetro as an open-source tool, we aim to empower chemists to tackle increasingly ambitious synthetic targets, accelerating progress in drug discovery, materials design, and beyond.
Thank you to arXiv for use of its open access interoperability. PaperDance 不是 arXiv 官方产品;中文卡片由大模型生成,请以原文为准。