# RetroMPA: A Molecular Property-Aware Auxiliary Framework for Enhancing Retrosynthesis Prediction

arXiv: https://arxiv.org/abs/2608.16111 · HTML: https://mlsanity.com/paper/2608.16111/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 21 of its 51 references that are in the map.
- First posted on arXiv 17 Aug 2026.

## Builds on (most cited first, 21 of 21)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [BLIP-2: Bootstrapping Language-Image Pre-training with Frozen Image Encoders and Large Language Models](https://mlsanity.com/paper/2301.12597/) (2023)
- [Multi-modal Molecule Structure-text Model for Text-based Retrieval and Editing](https://mlsanity.com/paper/2212.10789/) (2022)
- [Mol-Instructions: A Large-Scale Biomolecular Instruction Dataset for Large Language Models](https://mlsanity.com/paper/2306.08018/) (2023)
- [MolCA: Molecular Graph-Language Modeling with Cross-Modal Projector and Uni-Modal Adapter](https://mlsanity.com/paper/2310.12798/) (2023)
- [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)
- [ProGCL: Rethinking Hard Negative Mining in Graph Contrastive Learning](https://mlsanity.com/paper/2110.02027/) (2021)
- [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)
- [Root-aligned SMILES: A Tight Representation for Chemical Reaction Prediction](https://mlsanity.com/paper/2203.11444/) (2022)
- [MassSpecGym: A benchmark for the discovery and identification of molecules](https://mlsanity.com/paper/2410.23326/) (2024)
- [Improving Molecular Contrastive Learning via Faulty Negative Mitigation and Decomposed Fragment Contrast](https://mlsanity.com/paper/2202.09346/) (2022)
- [Chemical-Reaction-Aware Molecule Representation Learning](https://mlsanity.com/paper/2109.09888/) (2021)
- [Re-evaluating Retrosynthesis Algorithms with Syntheseus](https://mlsanity.com/paper/2310.19796/) (2023)
- [Retrosynthesis Prediction with Local Template Retrieval](https://mlsanity.com/paper/2306.04123/) (2023)
- [Models Matter: The Impact of Single-Step Retrosynthesis on Synthesis Planning](https://mlsanity.com/paper/2308.05522/) (2023)
- [Node-Aligned Graph-to-Graph (NAG2G): Elevating Template-Free Deep Learning Approaches in Single-Step Retrosynthesis](https://mlsanity.com/paper/2309.15798/) (2023)
- [Guiding Teacher Forcing with Seer Forcing for Neural Machine Translation](https://mlsanity.com/paper/2106.06751/) (2021)
- [Retrosynthesis prediction enhanced by in-silico reaction data augmentation](https://mlsanity.com/paper/2402.00086/) (2024)
- [Retro-Expert: Collaborative Reasoning for Interpretable Retrosynthesis](https://mlsanity.com/paper/2508.10967/) (2025)

## Abstract (arXiv)

Retrosynthesis is a cornerstone of drug discovery and organic synthesis. While data-driven deep learning models have shown remarkable progress, they autonomously learn reaction patterns from extensive datasets with limited integration of established chemical knowledge as priors. To address this limitation, we introduce RetroMPA, a molecular property-aware, post-hoc enhancement module that injects chemical knowledge into the retrosynthesis pipeline. Rather than functioning as an independent SMILES sequence generator, RetroMPA is a broadly applicable, model-agnostic chemical filter designed to recalibrate and optimize the predictive pathways of existing algorithms. This plug-and-play framework integrates seamlessly with a range of data-driven retrosynthesis methods, enhancing outputs without modifying model architecture or requiring resource-intensive retraining. By leveraging a property-aware latent embedding space, RetroMPA consistently improves top-1 accuracy across eight representative retrosynthesis models by an average of 5.50% on USPTO-50K. Furthermore, we validate its scalability on the large-scale USPTO-Full dataset, achieving an average improvement of about 2.03% across both template-based and template-free architectures. Wet-lab experiments provide preliminary support for the practical utility of the framework. These syntheses confirmed viable, previously unreported substrate combinations for classic reaction paradigms---specifically, Suzuki-Miyaura coupling, Bucherer reaction, and Friedel-Crafts acylation---suggesting that RetroMPA can operate beyond mere data fitting. The code is open-sourced at https://github.com/MengzhouLu/RetroMPA.