# MolGuidance: Advanced Guidance Strategies for Conditional Molecular Generation with Flow Matching

arXiv: https://arxiv.org/abs/2512.12198 · HTML: https://mlsanity.com/paper/2512.12198/

## Key facts

- Cited by 4 papers in the map (data through 14 Oct 2026).
- Placed in Flow matching, time series and science, one of 14 directions in Diffusion models.
- Builds on 32 of its 50 references that are in the map.
- First posted on arXiv 13 Dec 2025.

## Placed in

- Diffusion models / [Flow matching, time series and science](https://mlsanity.com/diffusion/flow-matching-time-series-and-science/)

## Builds on (most cited first, 30 of 32)

- [Diffusion Models Beat GANs on Image Synthesis](https://mlsanity.com/paper/2105.05233/) (2021)
- [Classifier-Free Diffusion Guidance](https://mlsanity.com/paper/2207.12598/) (2022)
- [Bootstrap your own latent: A new approach to self-supervised Learning](https://mlsanity.com/paper/2006.07733/) (2020)
- [MoleculeNet: A Benchmark for Molecular Machine Learning](https://mlsanity.com/paper/1703.00564/) (2017)
- [E(n) Equivariant Graph Neural Networks](https://mlsanity.com/paper/2102.09844/) (2021)
- [Automatic chemical design using a data-driven continuous representation of molecules](https://mlsanity.com/paper/1610.02415/) (2016)
- [Tensor field networks: Rotation- and translation-equivariant neural networks for 3D point clouds](https://mlsanity.com/paper/1802.08219/) (2018)
- [E(3)-Equivariant Graph Neural Networks for Data-Efficient and Accurate Interatomic Potentials](https://mlsanity.com/paper/2101.03164/) (2021)
- [Equivariant Diffusion for Molecule Generation in 3D](https://mlsanity.com/paper/2203.17003/) (2022)
- [Analyzing and Improving the Training Dynamics of Diffusion Models](https://mlsanity.com/paper/2312.02696/) (2023)
- [Discrete Flow Matching](https://mlsanity.com/paper/2407.15595/) (2024)
- [Generative Flows on Discrete State-Spaces: Enabling Multimodal Flows with Applications to Protein Co-Design](https://mlsanity.com/paper/2402.04997/) (2024)
- [Guiding a Diffusion Model with a Bad Version of Itself](https://mlsanity.com/paper/2406.02507/) (2024)
- [Flow Matching on General Geometries](https://mlsanity.com/paper/2302.03660/) (2023)
- [Molecular Graph Convolutions: Moving Beyond Fingerprints](https://mlsanity.com/paper/1603.00856/) (2016)
- [Adjoint Matching: Fine-tuning Flow and Diffusion Generative Models with Memoryless Stochastic Optimal Control](https://mlsanity.com/paper/2409.08861/) (2024)
- [Structure-based Drug Design with Equivariant Diffusion Models](https://mlsanity.com/paper/2210.13695/) (2022)
- [Geometric Latent Diffusion Models for 3D Molecule Generation](https://mlsanity.com/paper/2305.01140/) (2023)
- [Unlocking Guidance for Discrete State-Space Diffusion and Flow Models](https://mlsanity.com/paper/2406.01572/) (2024)
- [MiDi: Mixed Graph and 3D Denoising Diffusion for Molecule Generation](https://mlsanity.com/paper/2302.09048/) (2023)
- [Mixed Continuous and Categorical Flow Matching for 3D De Novo Molecule Generation](https://mlsanity.com/paper/2404.19739/) (2024)
- [No Training, No Problem: Rethinking Classifier-Free Guidance for Diffusion Models](https://mlsanity.com/paper/2407.02687/) (2024)
- [Navigating the Design Space of Equivariant Diffusion-Based Generative Models for De Novo 3D Molecule Generation](https://mlsanity.com/paper/2309.17296/) (2023)
- [ET-Flow: Equivariant Flow-Matching for Molecular Conformer Generation](https://mlsanity.com/paper/2410.22388/) (2024)
- [Inference-Time Scaling for Flow Models via Stochastic Generation and Rollover Budget Forcing](https://mlsanity.com/paper/2503.19385/) (2025)
- [Geometry-Complete Diffusion for 3D Molecule Generation and Optimization](https://mlsanity.com/paper/2302.04313/) (2023)
- [Diffusion Models without Classifier-free Guidance](https://mlsanity.com/paper/2502.12154/) (2025)
- [Adjoint Schr"odinger Bridge Sampler](https://mlsanity.com/paper/2506.22565/) (2025)
- [Exploring Discrete Flow Matching for 3D De Novo Molecule Generation](https://mlsanity.com/paper/2411.16644/) (2024)
- [Towards Unified and Lossless Latent Space for 3D Molecular Latent Diffusion Modeling](https://mlsanity.com/paper/2503.15567/) (2025)

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

- [MolCrystalFlow: Molecular Crystal Structure Prediction via Flow Matching](https://mlsanity.com/paper/2602.16020/) (2026)
- [Property-Guided Molecular Generation and Optimization via Latent Flows](https://mlsanity.com/paper/2603.26889/) (2026)
- [Language-Informed Flow Matching for Trend-Guided Structure-Based 3D Molecular Generation](https://mlsanity.com/paper/2608.31009/) (2026)
- [Graph Forward Distribution Matching for Molecular Inverse Design](https://mlsanity.com/paper/2609.32056/) (2026)

## Abstract (arXiv)

Key objectives in conditional molecular generation include ensuring chemical validity, aligning generated molecules with target properties, promoting structural diversity, and enabling efficient sampling for discovery. Recent advances in computer vision introduced a range of new guidance strategies for generative models, many of which can be adapted to support these goals. In this work, we integrate state-of-the-art guidance methods -- including classifier-free guidance, autoguidance, and model guidance -- in a leading molecule generation framework built on an SE(3)-equivariant flow matching process. We propose a hybrid guidance strategy that separately guides continuous and discrete molecular modalities -- operating on velocity fields and predicted logits, respectively -- while jointly optimizing their guidance scales via Bayesian optimization. Our implementation, benchmarked on the QM9 and QMe14S datasets, achieves new state-of-the-art performance in property alignment for de novo molecular generation. The generated molecules also exhibit high structural validity. Furthermore, we systematically compare the strengths and limitations of various guidance methods, offering insights into their broader applicability.