# SE(3)-Stochastic Flow Matching for Protein Backbone Generation

arXiv: https://arxiv.org/abs/2310.02391 · HTML: https://mlsanity.com/paper/2310.02391/

## Key facts

- Cited by 150 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 49 of its 106 references that are in the map.
- First posted on arXiv 3 Oct 2023.

## 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 49)

- [Flow Matching for Generative Modeling](https://mlsanity.com/paper/2210.02747/) (2022)
- [Flow Straight and Fast: Learning to Generate and Transfer Data with Rectified Flow](https://mlsanity.com/paper/2209.03003/) (2022)
- [Density estimation using Real NVP](https://mlsanity.com/paper/1605.08803/) (2016)
- [Building Normalizing Flows with Stochastic Interpolants](https://mlsanity.com/paper/2209.15571/) (2022)
- [Stochastic Interpolants: A Unifying Framework for Flows and Diffusions](https://mlsanity.com/paper/2303.08797/) (2023)
- [Improving and generalizing flow-based generative models with minibatch optimal transport](https://mlsanity.com/paper/2302.00482/) (2023)
- [Computational Optimal Transport](https://mlsanity.com/paper/1803.00567/) (2018)
- [Equivariant Diffusion for Molecule Generation in 3D](https://mlsanity.com/paper/2203.17003/) (2022)
- [Wasserstein GAN](https://mlsanity.com/paper/1701.07875/) (2017)
- [Diffusion Schr"odinger Bridge with Applications to Score-Based Generative Modeling](https://mlsanity.com/paper/2106.01357/) (2021)
- [GeoDiff: a Geometric Diffusion Model for Molecular Conformation Generation](https://mlsanity.com/paper/2203.02923/) (2022)
- [Learning Generative Models with Sinkhorn Divergences](https://mlsanity.com/paper/1706.00292/) (2017)
- [Multisample Flow Matching: Straightening Flows with Minibatch Couplings](https://mlsanity.com/paper/2304.14772/) (2023)
- [Equivariant Flows: Exact Likelihood Generative Learning for Symmetric Densities](https://mlsanity.com/paper/2006.02425/) (2020)
- [How to train your neural ODE: the world of Jacobian and kinetic regularization](https://mlsanity.com/paper/2002.02798/) (2020)
- [Riemannian Score-Based Generative Modelling](https://mlsanity.com/paper/2202.02763/) (2022)
- [SE(3) diffusion model with application to protein backbone generation](https://mlsanity.com/paper/2302.02277/) (2023)
- [I2SB: Image-to-Image Schr"odinger Bridge](https://mlsanity.com/paper/2302.05872/) (2023)
- [DeepJDOT: Deep Joint Distribution Optimal Transport for Unsupervised Domain Adaptation](https://mlsanity.com/paper/1803.10081/) (2018)
- [Same Same But DifferNet: Semi-Supervised Defect Detection with Normalizing Flows](https://mlsanity.com/paper/2008.12577/) (2020)
- [E(n) Equivariant Normalizing Flows](https://mlsanity.com/paper/2105.09016/) (2021)
- [TrajectoryNet: A Dynamic Optimal Transport Network for Modeling Cellular Dynamics](https://mlsanity.com/paper/2002.04461/) (2020)
- [Diffusion Schr"odinger Bridge Matching](https://mlsanity.com/paper/2303.16852/) (2023)
- [Riemannian Continuous Normalizing Flows](https://mlsanity.com/paper/2006.10605/) (2020)
- [Equivariant flow matching](https://mlsanity.com/paper/2306.15030/) (2023)
- [Unbalanced minibatch Optimal Transport; applications to Domain Adaptation](https://mlsanity.com/paper/2103.03606/) (2021)
- [Improving GANs Using Optimal Transport](https://mlsanity.com/paper/1803.05573/) (2018)
- [Riemannian Diffusion Models](https://mlsanity.com/paper/2208.07949/) (2022)
- [Equivariant 3D-Conditional Diffusion Models for Molecular Linker Design](https://mlsanity.com/paper/2210.05274/) (2022)
- [Protein structure generation via folding diffusion](https://mlsanity.com/paper/2209.15611/) (2022)

## Built on by (most cited first, 30 of 150)

- [Generative Flows on Discrete State-Spaces: Enabling Multimodal Flows with Applications to Protein Co-Design](https://mlsanity.com/paper/2402.04997/) (2024)
- [Iterated Denoising Energy Matching for Sampling from Boltzmann Densities](https://mlsanity.com/paper/2402.06121/) (2024)
- [Dirichlet Flow Matching with Applications to DNA Sequence Design](https://mlsanity.com/paper/2402.05841/) (2024)
- [AlphaFold Meets Flow Matching for Generating Protein Ensembles](https://mlsanity.com/paper/2402.04845/) (2024)
- [FlowMM: Generating Materials with Riemannian Flow Matching](https://mlsanity.com/paper/2406.04713/) (2024)
- [Fisher Flow Matching for Generative Modeling over Discrete Data](https://mlsanity.com/paper/2405.14664/) (2024)
- [Learning Robotic Manipulation Policies from Point Clouds with Conditional Flow Matching](https://mlsanity.com/paper/2409.07343/) (2024)
- [Proteina: Scaling Flow-based Protein Structure Generative Models](https://mlsanity.com/paper/2503.00710/) (2025)
- [Riemannian Flow Matching Policy for Robot Motion Learning](https://mlsanity.com/paper/2403.10672/) (2024)
- [Categorical Flow Matching on Statistical Manifolds](https://mlsanity.com/paper/2405.16441/) (2024)
- [FUDOKI: Discrete Flow-based Unified Understanding and Generation via Kinetic-Optimal Velocities](https://mlsanity.com/paper/2505.20147/) (2025)
- [Protein Conformation Generation via Force-Guided SE(3) Diffusion Models](https://mlsanity.com/paper/2403.14088/) (2024)
- [Improved motif-scaffolding with SE(3) flow matching](https://mlsanity.com/paper/2401.04082/) (2024)
- [SemlaFlow -- Efficient 3D Molecular Generation with Latent Attention and Equivariant Flow Matching](https://mlsanity.com/paper/2406.07266/) (2024)
- [Streaming Flow Policy: Simplifying diffusion/flow-matching policies by treating action trajectories as flow trajectories](https://mlsanity.com/paper/2505.21851/) (2025)
- [Flow-Based Policy for Online Reinforcement Learning](https://mlsanity.com/paper/2506.12811/) (2025)
- [Sequence-Augmented SE(3)-Flow Matching For Conditional Protein Backbone Generation](https://mlsanity.com/paper/2405.20313/) (2024)
- [Full-Atom Peptide Design based on Multi-modal Flow Matching](https://mlsanity.com/paper/2406.00735/) (2024)
- [La-Proteina: Atomistic Protein Generation via Partially Latent Flow Matching](https://mlsanity.com/paper/2507.09466/) (2025)
- [Flow matching achieves almost minimax optimal convergence](https://mlsanity.com/paper/2405.20879/) (2024)
- [Open Materials Generation with Stochastic Interpolants](https://mlsanity.com/paper/2502.02582/) (2025)
- [Physics vs Distributions: Pareto Optimal Flow Matching with Physics Constraints](https://mlsanity.com/paper/2506.08604/) (2025)
- [PPFlow: Target-aware Peptide Design with Torsional Flow Matching](https://mlsanity.com/paper/2405.06642/) (2024)
- [ActionFlow: Equivariant, Accurate, and Efficient Policies with Spatially Symmetric Flow Matching](https://mlsanity.com/paper/2409.04576/) (2024)
- [ProteinBench: A Holistic Evaluation of Protein Foundation Models](https://mlsanity.com/paper/2409.06744/) (2024)
- [Training Free Guided Flow Matching with Optimal Control](https://mlsanity.com/paper/2410.18070/) (2024)
- [Generative Modeling on Manifolds Through Mixture of Riemannian Diffusion Processes](https://mlsanity.com/paper/2310.07216/) (2023)
- [FlowMol3: Flow Matching for 3D De Novo Small-Molecule Generation](https://mlsanity.com/paper/2508.12629/) (2025)
- [Trivialized Momentum Facilitates Diffusion Generative Modeling on Lie Groups](https://mlsanity.com/paper/2405.16381/) (2024)
- [Fast and Robust Visuomotor Riemannian Flow Matching Policy](https://mlsanity.com/paper/2412.10855/) (2024)

## Abstract (arXiv)

The computational design of novel protein structures has the potential to impact numerous scientific disciplines greatly. Toward this goal, we introduce FoldFlow, a series of novel generative models of increasing modeling power based on the flow-matching paradigm over 3D rigid motions -- i.e. the group SE(3) -- enabling accurate modeling of protein backbones. We first introduce FoldFlow-Base, a simulation-free approach to learning deterministic continuous-time dynamics and matching invariant target distributions on SE(3). We next accelerate training by incorporating Riemannian optimal transport to create FoldFlow-OT, leading to the construction of both more simple and stable flows. Finally, we design FoldFlow-SFM, coupling both Riemannian OT and simulation-free training to learn stochastic continuous-time dynamics over SE(3). Our family of FoldFlow, generative models offers several key advantages over previous approaches to the generative modeling of proteins: they are more stable and faster to train than diffusion-based approaches, and our models enjoy the ability to map any invariant source distribution to any invariant target distribution over SE(3). Empirically, we validate FoldFlow, on protein backbone generation of up to 300 amino acids leading to high-quality designable, diverse, and novel samples.