# PMO-Dock: Benchmarking Docking, Specificity, and Generalization in Molecular Optimization

arXiv: https://arxiv.org/abs/2610.19011 · HTML: https://mlsanity.com/paper/2610.19011/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 11 of its 21 references that are in the map.
- First posted on arXiv 13 Oct 2026.

## Builds on (most cited first, 11 of 11)

- [Flow Network based Generative Models for Non-Iterative Diverse Candidate Generation](https://mlsanity.com/paper/2106.04399/) (2021)
- [Sample Efficiency Matters: A Benchmark for Practical Molecular Optimization](https://mlsanity.com/paper/2206.12411/) (2022)
- [Efficient Evolutionary Search Over Chemical Space with Large Language Models](https://mlsanity.com/paper/2406.16976/) (2024)
- [GenMol: A Drug Discovery Generalist with Discrete Diffusion](https://mlsanity.com/paper/2501.06158/) (2025)
- [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)
- [Tartarus: A Benchmarking Platform for Realistic And Practical Inverse Molecular Design](https://mlsanity.com/paper/2209.12487/) (2022)
- [Saturn: Sample-efficient Generative Molecular Design using Memory Manipulation](https://mlsanity.com/paper/2405.17066/) (2024)
- [We Should at Least Be Able to Design Molecules That Dock Well](https://mlsanity.com/paper/2006.16955/) (2020)
- [Beam Enumeration: Probabilistic Explainability For Sample Efficient Self-conditioned Molecular Design](https://mlsanity.com/paper/2309.13957/) (2023)
- [Small Molecule Optimization with Large Language Models](https://mlsanity.com/paper/2407.18897/) (2024)

## Abstract (arXiv)

The Practical Molecular Optimization (PMO) benchmark standardized evaluation in molecular optimization, but it is built on simple property-based oracles that do not capture structure-based drug design. As the field has moved to docking-based objectives, evaluation practice has become unstandardized, and different methods report results on different docking tasks, often without a shared protocol for fair comparison or sample-efficiency constraints. To address this, we introduce Practical Molecular Optimization for Docking (PMO-Dock), a benchmark and protocol for docking-based optimization consisting of 25 tasks covering hit generation, lead optimization, and a new specificity task requiring strong on-target binding while penalizing off-target interactions. The protocol separates model development from final evaluation: validation tasks are used for hyperparameter tuning, and test tasks are held out for final evaluation and are not used during development. Evaluation on the test tasks is done under a strict oracle budget to reflect realistic drug-discovery settings. We benchmark four diverse high-performing methods spanning different optimization paradigms, Saturn (reinforcement learning), GenMol (discrete diffusion), Genetic-guided GFlowNet, and ChemLlama (LLM-based evolutionary search). Our results show no universally best method across tasks, additional analyses of hyperparameter transfer (cross-task and cross-category) and sensitivity show that transfer is often limited and varies by method, motivating method-dependent selection strategies. This benchmark provides a concrete standard for evaluating generalization to unseen tasks and sample efficiency under a limited test-time oracle budget.