# Energy-Based Flow Matching for Generating 3D Molecular Structure

arXiv: https://arxiv.org/abs/2508.18949 · HTML: https://mlsanity.com/paper/2508.18949/

## 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 41 of its 68 references that are in the map.
- First posted on arXiv 26 Aug 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 41)

- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [Score-Based Generative Modeling through Stochastic Differential Equations](https://mlsanity.com/paper/2011.13456/) (2020)
- [Flow Matching for Generative Modeling](https://mlsanity.com/paper/2210.02747/) (2022)
- [Generative Modeling by Estimating Gradients of the Data Distribution](https://mlsanity.com/paper/1907.05600/) (2019)
- [Neural Ordinary Differential Equations](https://mlsanity.com/paper/1806.07366/) (2018)
- [Flow Straight and Fast: Learning to Generate and Transfer Data with Rectified Flow](https://mlsanity.com/paper/2209.03003/) (2022)
- [Consistency Models](https://mlsanity.com/paper/2303.01469/) (2023)
- [Building Normalizing Flows with Stochastic Interpolants](https://mlsanity.com/paper/2209.15571/) (2022)
- [Improving and generalizing flow-based generative models with minibatch optimal transport](https://mlsanity.com/paper/2302.00482/) (2023)
- [Tensor field networks: Rotation- and translation-equivariant neural networks for 3D point clouds](https://mlsanity.com/paper/1802.08219/) (2018)
- [Equivariant Diffusion for Molecule Generation in 3D](https://mlsanity.com/paper/2203.17003/) (2022)
- [GeoDiff: a Geometric Diffusion Model for Molecular Conformation Generation](https://mlsanity.com/paper/2203.02923/) (2022)
- [Analog Bits: Generating Discrete Data using Diffusion Models with Self-Conditioning](https://mlsanity.com/paper/2208.04202/) (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)
- [Flow Matching Guide and Code](https://mlsanity.com/paper/2412.06264/) (2024)
- [Multisample Flow Matching: Straightening Flows with Minibatch Couplings](https://mlsanity.com/paper/2304.14772/) (2023)
- [Flow Matching on General Geometries](https://mlsanity.com/paper/2302.03660/) (2023)
- [Torsional Diffusion for Molecular Conformer Generation](https://mlsanity.com/paper/2206.01729/) (2022)
- [Diffusion probabilistic modeling of protein backbones in 3D for the motif-scaffolding problem](https://mlsanity.com/paper/2206.04119/) (2022)
- [SE(3) diffusion model with application to protein backbone generation](https://mlsanity.com/paper/2302.02277/) (2023)
- [e3nn: Euclidean Neural Networks](https://mlsanity.com/paper/2207.09453/) (2022)
- [SE(3)-Stochastic Flow Matching for Protein Backbone Generation](https://mlsanity.com/paper/2310.02391/) (2023)
- [EquiBind: Geometric Deep Learning for Drug Binding Structure Prediction](https://mlsanity.com/paper/2202.05146/) (2022)
- [D-Flow: Differentiating through Flows for Controlled Generation](https://mlsanity.com/paper/2402.14017/) (2024)
- [Protein structure generation via folding diffusion](https://mlsanity.com/paper/2209.15611/) (2022)
- [AlphaFold Meets Flow Matching for Generating Protein Ensembles](https://mlsanity.com/paper/2402.04845/) (2024)
- [Poisson Flow Generative Models](https://mlsanity.com/paper/2209.11178/) (2022)
- [PFGM++: Unlocking the Potential of Physics-Inspired Generative Models](https://mlsanity.com/paper/2302.04265/) (2023)
- [Riemannian Flow Matching Policy for Robot Motion Learning](https://mlsanity.com/paper/2403.10672/) (2024)

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

- [Flow-based Extremal Mathematical Structure Discovery](https://mlsanity.com/paper/2601.18005/) (2026)
- [Driving Reaction Trajectories via Latent Flow Matching](https://mlsanity.com/paper/2602.10476/) (2026)
- [Generating Physically Consistent Molecules with Energy-Based Models](https://mlsanity.com/paper/2605.18381/) (2026)
- [Composing Flow-Matching Energies with Known Physics: Generation, OOD Detection, and Inversion on PDE Fields](https://mlsanity.com/paper/2608.18004/) (2026)

## Abstract (arXiv)

Molecular structure generation is a fundamental problem that involves determining the 3D positions of molecules' constituents. It has crucial biological applications, such as molecular docking, protein folding, and molecular design. Recent advances in generative modeling, such as diffusion models and flow matching, have made great progress on these tasks by modeling molecular conformations as a distribution. In this work, we focus on flow matching and adopt an energy-based perspective to improve training and inference of structure generation models. Our view results in a mapping function, represented by a deep network, that is directly learned to textititeratively map random configurations, i.e. samples from the source distribution, to target structures, i.e. points in the data manifold. This yields a conceptually simple and empirically effective flow matching setup that is theoretically justified and has interesting connections to fundamental properties such as idempotency and stability, as well as the empirically useful techniques such as structure refinement in AlphaFold. Experiments on protein docking as well as protein backbone generation consistently demonstrate the method's effectiveness, where it outperforms recent baselines of task-associated flow matching and diffusion models, using a similar computational budget.