# MARS: A Motif-based Autoregressive Model for Retrosynthesis Prediction

arXiv: https://arxiv.org/abs/2209.13178 · HTML: https://mlsanity.com/paper/2209.13178/

## Key facts

- Cited by 8 papers in the map (data through 14 Oct 2026).
- Builds on 26 of its 50 references that are in the map.
- First posted on arXiv 27 Sep 2022.

## Builds on (most cited first, 26 of 26)

- [Adam: A Method for Stochastic Optimization](https://mlsanity.com/paper/1412.6980/) (2014)
- [PyTorch: An Imperative Style, High-Performance Deep Learning Library](https://mlsanity.com/paper/1912.01703/) (2019)
- [Semi-Supervised Classification with Graph Convolutional Networks](https://mlsanity.com/paper/1609.02907/) (2016)
- [Graph Attention Networks](https://mlsanity.com/paper/1710.10903/) (2017)
- [Inductive Representation Learning on Large Graphs](https://mlsanity.com/paper/1706.02216/) (2017)
- [SGDR: Stochastic Gradient Descent with Warm Restarts](https://mlsanity.com/paper/1608.03983/) (2016)
- [A Comprehensive Survey on Graph Neural Networks](https://mlsanity.com/paper/1901.00596/) (2019)
- [Fast Graph Representation Learning with PyTorch Geometric](https://mlsanity.com/paper/1903.02428/) (2019)
- [Empirical Evaluation of Gated Recurrent Neural Networks on Sequence Modeling](https://mlsanity.com/paper/1412.3555/) (2014)
- [Gated Graph Sequence Neural Networks](https://mlsanity.com/paper/1511.05493/) (2015)
- [Junction Tree Variational Autoencoder for Molecular Graph Generation](https://mlsanity.com/paper/1802.04364/) (2018)
- [Masked Label Prediction: Unified Message Passing Model for Semi-Supervised Classification](https://mlsanity.com/paper/2009.03509/) (2020)
- [MolGAN: An implicit generative model for small molecular graphs](https://mlsanity.com/paper/1805.11973/) (2018)
- [Graph Convolutional Policy Network for Goal-Directed Molecular Graph Generation](https://mlsanity.com/paper/1806.02473/) (2018)
- [GraphAF: a Flow-based Autoregressive Model for Molecular Graph Generation](https://mlsanity.com/paper/2001.09382/) (2020)
- [Retrosynthesis Prediction with Conditional Graph Logic Network](https://mlsanity.com/paper/2001.01408/) (2020)
- [Molecule Edit Graph Attention Network: Modeling Chemical Reactions as Sequences of Graph Edits](https://mlsanity.com/paper/2006.15426/) (2020)
- [Retrosynthetic reaction prediction using neural sequence-to-sequence models](https://mlsanity.com/paper/1706.01643/) (2017)
- [A Graph to Graphs Framework for Retrosynthesis Prediction](https://mlsanity.com/paper/2003.12725/) (2020)
- [MolecularRNN: Generating realistic molecular graphs with optimized properties](https://mlsanity.com/paper/1905.13372/) (2019)
- [RetroXpert: Decompose Retrosynthesis Prediction like a Chemist](https://mlsanity.com/paper/2011.02893/) (2020)
- [Learning Graph Models for Retrosynthesis Prediction](https://mlsanity.com/paper/2006.07038/) (2020)
- [Energy-based View of Retrosynthesis](https://mlsanity.com/paper/2007.13437/) (2020)
- [Learning to Make Generalizable and Diverse Predictions for Retrosynthesis](https://mlsanity.com/paper/1910.09688/) (2019)
- [RetroComposer: Composing Templates for Template-Based Retrosynthesis Prediction](https://mlsanity.com/paper/2112.11225/) (2021)
- [G2GT: Retrosynthesis Prediction with Graph to Graph Attention Neural Network and Self-Training](https://mlsanity.com/paper/2204.08608/) (2022)

## Built on by (most cited first, 8 of 8)

- [Graph Neural Networks in Modern AI-aided Drug Discovery](https://mlsanity.com/paper/2506.06915/) (2025)
- [Node-Aligned Graph-to-Graph (NAG2G): Elevating Template-Free Deep Learning Approaches in Single-Step Retrosynthesis](https://mlsanity.com/paper/2309.15798/) (2023)
- [Preference Optimization for Molecule Synthesis with Conditional Residual Energy-based Models](https://mlsanity.com/paper/2406.02066/) (2024)
- [A Unified View of Deep Learning for Reaction and Retrosynthesis Prediction: Current Status and Future Challenges](https://mlsanity.com/paper/2306.15890/) (2023)
- [RLSynC: Offline-Online Reinforcement Learning for Synthon Completion](https://mlsanity.com/paper/2309.02671/) (2023)
- [MotifRetro: Exploring the Combinability-Consistency Trade-offs in retrosynthesis via Dynamic Motif Editing](https://mlsanity.com/paper/2305.15153/) (2023)
- [ConfRetro: a 3D-aware template-free method for enhancing retrosynthesis via molecular conformer information](https://mlsanity.com/paper/2501.12434/) (2025)
- [POINT2: A Polymer Informatics Training and Testing Database](https://mlsanity.com/paper/2503.23491/) (2025)

## Abstract (arXiv)

Retrosynthesis is a major task for drug discovery. It is formulated as a graph-generating problem by many existing approaches. Specifically, these methods firstly identify the reaction center, and break target molecule accordingly to generate synthons. Reactants are generated by either adding atoms sequentially to synthon graphs or directly adding proper leaving groups. However, both two strategies suffer since adding atoms results in a long prediction sequence which increases generation difficulty, while adding leaving groups can only consider the ones in the training set which results in poor generalization. In this paper, we propose a novel end-to-end graph generation model for retrosynthesis prediction, which sequentially identifies the reaction center, generates the synthons, and adds motifs to the synthons to generate reactants. Since chemically meaningful motifs are bigger than atoms and smaller than leaving groups, our method enjoys lower prediction complexity than adding atoms and better generalization than adding leaving groups. Experiments on a benchmark dataset show that the proposed model significantly outperforms previous state-of-the-art algorithms.