# Pretraining Generative Flow Networks with Inexpensive Rewards for Molecular Graph Generation

arXiv: https://arxiv.org/abs/2503.06337 · HTML: https://mlsanity.com/paper/2503.06337/

## Key facts

- Cited by 4 papers in the map (data through 14 Oct 2026).
- Builds on 51 of its 81 references that are in the map.
- First posted on arXiv 8 Mar 2025.

## Builds on (most cited first, 30 of 51)

- [Language Models are Few-Shot Learners](https://mlsanity.com/paper/2005.14165/) (2020)
- [Graph Attention Networks](https://mlsanity.com/paper/1710.10903/) (2017)
- [Scaling Laws for Neural Language Models](https://mlsanity.com/paper/2001.08361/) (2020)
- [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)
- [Flow Network based Generative Models for Non-Iterative Diverse Candidate Generation](https://mlsanity.com/paper/2106.04399/) (2021)
- [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)
- [GuacaMol: Benchmarking Models for De Novo Molecular Design](https://mlsanity.com/paper/1811.09621/) (2018)
- [GFlowNet Foundations](https://mlsanity.com/paper/2111.09266/) (2021)
- [Score-based Generative Modeling of Graphs via the System of Stochastic Differential Equations](https://mlsanity.com/paper/2202.02514/) (2022)
- [Molecular Sets (MOSES): A Benchmarking Platform for Molecular Generation Models](https://mlsanity.com/paper/1811.12823/) (2018)
- [Molecular De Novo Design through Deep Reinforcement Learning](https://mlsanity.com/paper/1704.07555/) (2017)
- [Therapeutics Data Commons: Machine Learning Datasets and Tasks for Drug Discovery and Development](https://mlsanity.com/paper/2102.09548/) (2021)
- [Trajectory balance: Improved credit assignment in GFlowNets](https://mlsanity.com/paper/2201.13259/) (2022)
- [DeeperGCN: All You Need to Train Deeper GCNs](https://mlsanity.com/paper/2006.07739/) (2020)
- [Hierarchical Generation of Molecular Graphs using Structural Motifs](https://mlsanity.com/paper/2002.03230/) (2020)
- [Optimization of Molecules via Deep Reinforcement Learning](https://mlsanity.com/paper/1810.08678/) (2018)
- [GraphDF: A Discrete Flow Model for Molecular Graph Generation](https://mlsanity.com/paper/2102.01189/) (2021)
- [Revisiting Fundamentals of Experience Replay](https://mlsanity.com/paper/2007.06700/) (2020)
- [Behavior From the Void: Unsupervised Active Pre-Training](https://mlsanity.com/paper/2103.04551/) (2021)
- [Biological Sequence Design with GFlowNets](https://mlsanity.com/paper/2203.04115/) (2022)
- [Deep Reinforcement Learning for De-Novo Drug Design](https://mlsanity.com/paper/1711.10907/) (2017)
- [Bayesian Structure Learning with Generative Flow Networks](https://mlsanity.com/paper/2202.13903/) (2022)
- [MARS: Markov Molecular Sampling for Multi-objective Drug Discovery](https://mlsanity.com/paper/2103.10432/) (2021)
- [Generative Flow Networks for Discrete Probabilistic Modeling](https://mlsanity.com/paper/2202.01361/) (2022)
- [Multi-Objective GFlowNets](https://mlsanity.com/paper/2210.12765/) (2022)
- [Exploring Chemical Space with Score-based Out-of-distribution Generation](https://mlsanity.com/paper/2206.07632/) (2022)
- [Amortizing intractable inference in diffusion models for vision, language, and control](https://mlsanity.com/paper/2405.20971/) (2024)
- [Robust Scheduling with GFlowNets](https://mlsanity.com/paper/2302.05446/) (2023)

## Built on by (most cited first, 4 of 4)

- [Compositional Flows for 3D Molecule and Synthesis Pathway Co-design](https://mlsanity.com/paper/2504.08051/) (2025)
- [Synthesizable Molecular Generation via Soft-constrained GFlowNets with Rich Chemical Priors](https://mlsanity.com/paper/2602.04119/) (2026)
- [Flow of Spans: Generalizing Language Models to Dynamic Span-Vocabulary via GFlowNets](https://mlsanity.com/paper/2602.10583/) (2026)
- [SNACK: A Sequential Notation Framework for Probabilistic Graph Generation](https://mlsanity.com/paper/2610.19781/) (2026)

## Abstract (arXiv)

Generative Flow Networks (GFlowNets) have recently emerged as a suitable framework for generating diverse and high-quality molecular structures by learning from rewards treated as unnormalized distributions. Previous works in this framework often restrict exploration by using predefined molecular fragments as building blocks, limiting the chemical space that can be accessed. In this work, we introduce Atomic GFlowNets (A-GFNs), a foundational generative model leveraging individual atoms as building blocks to explore drug-like chemical space more comprehensively. We propose an unsupervised pre-training approach using drug-like molecule datasets, which teaches A-GFNs about inexpensive yet informative molecular descriptors such as drug-likeliness, topological polar surface area, and synthetic accessibility scores. These properties serve as proxy rewards, guiding A-GFNs towards regions of chemical space that exhibit desirable pharmacological properties. We further implement a goal-conditioned finetuning process, which adapts A-GFNs to optimize for specific target properties. In this work, we pretrain A-GFN on a subset of ZINC dataset, and by employing robust evaluation metrics we show the effectiveness of our approach when compared to other relevant baseline methods for a wide range of drug design tasks. The code is accessible at https://github.com/diamondspark/AGFN.