# OctMole: Multiscale 3D Molecular Generation with Hierarchical Spatial Flows

arXiv: https://arxiv.org/abs/2610.16586 · HTML: https://mlsanity.com/paper/2610.16586/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 23 of its 27 references that are in the map.
- First posted on arXiv 12 Oct 2026.

## Builds on (most cited first, 23 of 23)

- [Flow Matching for Generative Modeling](https://mlsanity.com/paper/2210.02747/) (2022)
- [Structured 3D Latents for Scalable and Versatile 3D Generation](https://mlsanity.com/paper/2412.01506/) (2024)
- [Equivariant Diffusion for Molecule Generation in 3D](https://mlsanity.com/paper/2203.17003/) (2022)
- [DiffDock: Diffusion Steps, Twists, and Turns for Molecular Docking](https://mlsanity.com/paper/2210.01776/) (2022)
- [Generative Flows on Discrete State-Spaces: Enabling Multimodal Flows with Applications to Protein Co-Design](https://mlsanity.com/paper/2402.04997/) (2024)
- [GEOM: Energy-annotated molecular conformations for property prediction and molecular generation](https://mlsanity.com/paper/2006.05531/) (2020)
- [Geometric Latent Diffusion Models for 3D Molecule Generation](https://mlsanity.com/paper/2305.01140/) (2023)
- [Equivariant 3D-Conditional Diffusion Models for Molecular Linker Design](https://mlsanity.com/paper/2210.05274/) (2022)
- [MiDi: Mixed Graph and 3D Denoising Diffusion for Molecule Generation](https://mlsanity.com/paper/2302.09048/) (2023)
- [OctFusion: Octree-based Diffusion Models for 3D Shape Generation](https://mlsanity.com/paper/2408.14732/) (2024)
- [SemlaFlow -- Efficient 3D Molecular Generation with Latent Attention and Equivariant Flow Matching](https://mlsanity.com/paper/2406.07266/) (2024)
- [3D molecule generation by denoising voxel grids](https://mlsanity.com/paper/2306.07473/) (2023)
- [Octree Transformer: Autoregressive 3D Shape Generation on Hierarchically Structured Sequences](https://mlsanity.com/paper/2111.12480/) (2021)
- [Trans-Dimensional Generative Modeling via Jump Diffusion Models](https://mlsanity.com/paper/2305.16261/) (2023)
- [OctGPT: Octree-based Multiscale Autoregressive Models for 3D Shape Generation](https://mlsanity.com/paper/2504.09975/) (2025)
- [UniGEM: A Unified Approach to Generation and Property Prediction for Molecules](https://mlsanity.com/paper/2410.10516/) (2024)
- [ShEPhERD: Diffusing shape, electrostatics, and pharmacophores for bioisosteric drug design](https://mlsanity.com/paper/2411.04130/) (2024)
- [TABASCO: A Fast, Simplified Model for Molecular Generation with Improved Physical Quality](https://mlsanity.com/paper/2507.00899/) (2025)
- [Unified Guidance for Geometry-Conditioned Molecular Generation](https://mlsanity.com/paper/2501.02526/) (2025)
- [Shape-conditioned 3D Molecule Generation via Equivariant Diffusion Models](https://mlsanity.com/paper/2308.11890/) (2023)
- [Unified Cross-Scale 3D Generation and Understanding via Autoregressive Modeling](https://mlsanity.com/paper/2503.16278/) (2025)
- [Branching Flows: Discrete, Continuous, and Manifold Flow Matching with Splits and Deletions](https://mlsanity.com/paper/2511.09465/) (2025)
- [Zatom-1: Towards a Multimodal Foundation Model for 3D Molecules and Materials](https://mlsanity.com/paper/2602.22251/) (2026)

## Abstract (arXiv)

Generating accurate 3D molecules requires jointly determining a variable number of atoms, their identities, and geometry across spatial scales: global shape emerges coarsely, whereas chemical bonds demand fine local precision. Existing atom-based diffusion and flow models operate largely at a single scale, while dense spatial fields become costly at high resolution. We introduce OctMole, a multiscale octree flow framework for 3D molecular generation. A hierarchical occupancy flow progressively resolves sparse molecular support from coarse to fine, and a joint atom flow assigns atom types and continuous in-cell offsets to occupied leaves. This decomposition combines efficient global structure with subcell geometric precision, while cell corruption improves robustness to generated support. On QM9 and GEOM-DRUG, OctMole achieves strong chemical, distributional, and geometric quality, with particularly clear gains over Uni-3DAR on GEOM-DRUG and substantial efficiency gains over dense 3D generation. As an additional capability, intermediate occupancy states and selected regions provide spatial conditioning without task-specific retraining, supporting multiscale shape conditioning, regional editing, linker generation, and shape interpolation. Code and pretrained checkpoints are available at https://github.com/octree-nn/octmole and https://huggingface.co/Disembo/octmole, respectively.