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Motivation: Retrosynthesis planning poses a formidable challenge in the organic chemical industry. Single-step retrosynthesis prediction, a crucial step in the planning process, has witnessed a surge in interest in recent years due to…

Chemical Physics · Physics 2024-04-22 Kaipeng Zeng , Bo yang , Xin Zhao , Yu Zhang , Fan Nie , Xiaokang Yang , Yaohui Jin , Yanyan Xu

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…

Machine Learning · Computer Science 2025-10-21 Jiaxi Zhuang , Yu Zhang , Aimin Zhou , Ying Qian

The main target of retrosynthesis is to recursively decompose desired molecules into available building blocks. Existing template-based retrosynthesis methods follow a template selection stereotype and suffer from limited training…

Chemical Physics · Physics 2022-12-26 Chaochao Yan , Peilin Zhao , Chan Lu , Yang Yu , Junzhou Huang

Retrosynthesis prediction is one of the fundamental challenges in organic synthesis. The task is to predict the reactants given a core product. With the advancement of machine learning, computer-aided synthesis planning has gained…

Chemical Physics · Physics 2022-02-01 Yue Wan , Benben Liao , Chang-Yu Hsieh , Shengyu Zhang

Retrosynthesis plays a crucial role in the fields of organic synthesis and drug development, where the goal is to identify suitable reactants that can yield a target product molecule. Although existing methods have achieved notable success,…

Machine Learning · Computer Science 2025-10-20 Jiaxi Zhuang , Yu Zhang , Yan Zhang , Ying Qian , Aimin Zhou

Synthesis planning and reaction outcome prediction are two fundamental problems in computer-aided organic chemistry for which a variety of data-driven approaches have emerged. Natural language approaches that model each problem as a…

Machine Learning · Computer Science 2021-10-20 Zhengkai Tu , Connor W. Coley

A fundamental problem in computational chemistry is to find a set of reactants to synthesize a target molecule, a.k.a. retrosynthesis prediction. Existing state-of-the-art methods rely on matching the target molecule with a large set of…

Machine Learning · Computer Science 2021-08-23 Chence Shi , Minkai Xu , Hongyu Guo , Ming Zhang , Jian Tang

Retrosynthesis prediction is a fundamental problem in organic synthesis, where the task is to identify precursor molecules that can be used to synthesize a target molecule. A key consideration in building neural models for this task is…

Machine Learning · Computer Science 2021-06-07 Vignesh Ram Somnath , Charlotte Bunne , Connor W. Coley , Andreas Krause , Regina Barzilay

Retrosynthesis involves determining a sequence of reactions to synthesize complex molecules from simpler precursors. As this poses a challenge in organic chemistry, machine learning has offered solutions, particularly for predicting…

Machine Learning · Computer Science 2023-10-12 Mikołaj Sacha , Michał Sadowski , Piotr Kozakowski , Ruard van Workum , Stanisław Jastrzębski

Retrosynthesis, which predicts the reactants of a given target molecule, is an essential task for drug discovery. In recent years, the machine learing based retrosynthesis methods have achieved promising results. In this work, we introduce…

Artificial Intelligence · Computer Science 2023-06-08 Shufang Xie , Rui Yan , Junliang Guo , Yingce Xia , Lijun Wu , Tao Qin

We investigated the effect of different training scenarios on predicting the (retro)synthesis of chemical compounds using a text-like representation of chemical reactions (SMILES) and Natural Language Processing neural network Transformer…

Machine Learning · Computer Science 2021-01-27 Igor V. Tetko , Pavel Karpov , Ruud Van Deursen , Guillaume Godin

Template-free retrosynthesis methods treat the task as black-box sequence generation, limiting learning efficiency, while semi-template approaches rely on rigid reaction libraries that constrain generalization. We address this gap with a…

Machine Learning · Computer Science 2026-02-16 Chenguang Wang , Zihan Zhou , Lei Bai , Tianshu Yu

Retrosynthesis is the process of recursively decomposing target molecules into available building blocks. It plays an important role in solving problems in organic synthesis planning. To automate or assist in the retrosynthesis analysis,…

Quantitative Methods · Quantitative Biology 2020-11-06 Chaochao Yan , Qianggang Ding , Peilin Zhao , Shuangjia Zheng , Jinyu Yang , Yang Yu , Junzhou Huang

We propose a new model for making generalizable and diverse retrosynthetic reaction predictions. Given a target compound, the task is to predict the likely chemical reactants to produce the target. This generative task can be framed as a…

Machine Learning · Computer Science 2019-10-23 Benson Chen , Tianxiao Shen , Tommi S. Jaakkola , Regina Barzilay

Synthesis planning is the process of recursively decomposing target molecules into available precursors. Computer-aided retrosynthesis can potentially assist chemists in designing synthetic routes, but at present it is cumbersome and…

Chemical Physics · Physics 2019-07-04 Shuangjia Zheng , Jiahua Rao , Zhongyue Zhang , Jun Xu , Yuedong Yang

Retrosynthesis planning remains a central challenge in molecular discovery due to the vast and complex chemical reaction space. While traditional template-based methods offer tractability, they suffer from poor scalability and limited…

Machine Learning · Computer Science 2025-07-31 Nguyen Xuan-Vu , Daniel P Armstrong , Zlatko Jončev , Philippe Schwaller

We present an attention-based Transformer model for automatic retrosynthesis route planning. Our approach starts from reactants prediction of single-step organic reactions for given products, followed by Monte Carlo tree search-based…

Quantitative Methods · Quantitative Biology 2019-06-07 Kangjie Lin , Youjun Xu , Jianfeng Pei , Luhua Lai

Various template-based and template-free approaches have been proposed for single-step retrosynthesis prediction in recent years. While these approaches demonstrate strong performance from a data-driven metrics standpoint, many model…

Machine Learning · Computer Science 2023-08-15 Kevin Zhang , Vipul Mann , Venkat Venkatasubramanian

Despite the acknowledged capability of template-free models in exploring unseen reaction spaces compared to template-based models for retrosynthesis prediction, their ability to venture beyond established boundaries remains relatively…

Chemical Physics · Physics 2024-03-08 Shuan Chen , Yousung Jung

The prediction of organic reaction outcomes is a fundamental problem in computational chemistry. Since a reaction may involve hundreds of atoms, fully exploring the space of possible transformations is intractable. The current solution…

Machine Learning · Computer Science 2018-01-01 Wengong Jin , Connor W. Coley , Regina Barzilay , Tommi Jaakkola
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