# Oracle-Budgeted Molecular Optimization with Short-Term Graph Memory

arXiv: https://arxiv.org/abs/2607.28437 · HTML: https://mlsanity.com/paper/2607.28437/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 16 of its 30 references that are in the map.
- First posted on arXiv 30 Jul 2026.

## Builds on (most cited first, 16 of 16)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [How Powerful are Graph Neural Networks?](https://mlsanity.com/paper/1810.00826/) (2018)
- [Strategies for Pre-training Graph Neural Networks](https://mlsanity.com/paper/1905.12265/) (2019)
- [Recipe for a General, Powerful, Scalable Graph Transformer](https://mlsanity.com/paper/2205.12454/) (2022)
- [DiGress: Discrete Denoising diffusion for graph generation](https://mlsanity.com/paper/2209.14734/) (2022)
- [Flow Network based Generative Models for Non-Iterative Diverse Candidate Generation](https://mlsanity.com/paper/2106.04399/) (2021)
- [Molecular De Novo Design through Deep Reinforcement Learning](https://mlsanity.com/paper/1704.07555/) (2017)
- [GraphDF: A Discrete Flow Model for Molecular Graph Generation](https://mlsanity.com/paper/2102.01189/) (2021)
- [Sample Efficiency Matters: A Benchmark for Practical Molecular Optimization](https://mlsanity.com/paper/2206.12411/) (2022)
- [Hit and Lead Discovery with Explorative RL and Fragment-based Molecule Generation](https://mlsanity.com/paper/2110.01219/) (2021)
- [Gotta be SAFE: A New Framework for Molecular Design](https://mlsanity.com/paper/2310.10773/) (2023)
- [Genetic-guided GFlowNets for Sample Efficient Molecular Optimization](https://mlsanity.com/paper/2402.05961/) (2024)
- [3DLinker: An E(3) Equivariant Variational Autoencoder for Molecular Linker Design](https://mlsanity.com/paper/2205.07309/) (2022)
- [Generative Modelling of Structurally Constrained Graphs](https://mlsanity.com/paper/2406.17341/) (2024)
- [Latent Bayesian Optimization via Autoregressive Normalizing Flows](https://mlsanity.com/paper/2504.14889/) (2025)
- [Self-Supervised Learning on Molecular Graphs: A Systematic Investigation of Masking Design](https://mlsanity.com/paper/2512.07064/) (2025)

## Abstract (arXiv)

Molecular optimization is commonly performed under a limited oracle budget, which makes deciding what to evaluate as important as deciding what to generate. We introduce short-term graph memory, a plug-in module that preserves the generator architecture and native update rule while learning from previously evaluated molecules to prioritize subsequent oracle queries. The module maintains an online graph neural surrogate that pre-screens each round's candidate pool, so the fixed oracle budget is spent on molecules with higher predicted utility. Applied to a fragment-based generator on a standard molecular optimization benchmark, it improves the mean top-10 score at no extra oracle cost and never falls behind the base on any oracle; the gain extends to all four generators we tested at a tight budget of one thousand calls. We then analyze how surrogate-guided selection interacts with the exploration and exploitation behavior of different generators. Its benefit at larger budgets is consistent with two properties of the backbone: how broadly it searches, and how effectively its native search already exploits oracle feedback. We provide a simple way to spend a fixed oracle budget more selectively, and evidence on which generators benefit from it.