# Generative Flows on Discrete State-Spaces: Enabling Multimodal Flows with Applications to Protein Co-Design

arXiv: https://arxiv.org/abs/2402.04997 · HTML: https://mlsanity.com/paper/2402.04997/

## Key facts

- Cited by 305 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 54 of its 84 references that are in the map.
- First posted on arXiv 7 Feb 2024.

## 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 54)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [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)
- [Deep Unsupervised Learning using Nonequilibrium Thermodynamics](https://mlsanity.com/paper/1503.03585/) (2015)
- [Flow Matching for Generative Modeling](https://mlsanity.com/paper/2210.02747/) (2022)
- [Auto-Encoding Variational Bayes](https://mlsanity.com/paper/1312.6114/) (2013)
- [Flow Straight and Fast: Learning to Generate and Transfer Data with Rectified Flow](https://mlsanity.com/paper/2209.03003/) (2022)
- [Elucidating the Design Space of Diffusion-Based Generative Models](https://mlsanity.com/paper/2206.00364/) (2022)
- [Decoupled Weight Decay Regularization](https://mlsanity.com/paper/1711.05101/) (2017)
- [Structured Denoising Diffusion Models in Discrete State-Spaces](https://mlsanity.com/paper/2107.03006/) (2021)
- [Diffusion-LM Improves Controllable Text Generation](https://mlsanity.com/paper/2205.14217/) (2022)
- [Building Normalizing Flows with Stochastic Interpolants](https://mlsanity.com/paper/2209.15571/) (2022)
- [Discrete Diffusion Modeling by Estimating the Ratios of the Data Distribution](https://mlsanity.com/paper/2310.16834/) (2023)
- [SiT: Exploring Flow and Diffusion-based Generative Models with Scalable Interpolant Transformers](https://mlsanity.com/paper/2401.08740/) (2024)
- [Scaling Vision Transformers to 22 Billion Parameters](https://mlsanity.com/paper/2302.05442/) (2023)
- [Argmax Flows and Multinomial Diffusion: Learning Categorical Distributions](https://mlsanity.com/paper/2102.05379/) (2021)
- [DiGress: Discrete Denoising diffusion for graph generation](https://mlsanity.com/paper/2209.14734/) (2022)
- [Reinforced Self-Training (ReST) for Language Modeling](https://mlsanity.com/paper/2308.08998/) (2023)
- [A Continuous Time Framework for Discrete Denoising Models](https://mlsanity.com/paper/2205.14987/) (2022)
- [DiffuSeq: Sequence to Sequence Text Generation with Diffusion Models](https://mlsanity.com/paper/2210.08933/) (2022)
- [TabDDPM: Modelling Tabular Data with Diffusion Models](https://mlsanity.com/paper/2209.15421/) (2022)
- [Analog Bits: Generating Discrete Data using Diffusion Models with Self-Conditioning](https://mlsanity.com/paper/2208.04202/) (2022)
- [GFlowNet Foundations](https://mlsanity.com/paper/2111.09266/) (2021)
- [Flow Matching on General Geometries](https://mlsanity.com/paper/2302.03660/) (2023)
- [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)
- [Continuous diffusion for categorical data](https://mlsanity.com/paper/2211.15089/) (2022)
- [SSD-LM: Semi-autoregressive Simplex-based Diffusion Language Model for Text Generation and Modular Control](https://mlsanity.com/paper/2210.17432/) (2022)
- [A Variational Perspective on Diffusion-Based Generative Models and Score Matching](https://mlsanity.com/paper/2106.02808/) (2021)
- [Score-based Continuous-time Discrete Diffusion Models](https://mlsanity.com/paper/2211.16750/) (2022)

## Built on by (most cited first, 30 of 305)

- [Simple and Effective Masked Diffusion Language Models](https://mlsanity.com/paper/2406.07524/) (2024)
- [Simplified and Generalized Masked Diffusion for Discrete Data](https://mlsanity.com/paper/2406.04329/) (2024)
- [Discrete Flow Matching](https://mlsanity.com/paper/2407.15595/) (2024)
- [Remasking Discrete Diffusion Models with Inference-Time Scaling](https://mlsanity.com/paper/2503.00307/) (2025)
- [Simple Guidance Mechanisms for Discrete Diffusion Models](https://mlsanity.com/paper/2412.10193/) (2024)
- [LLaDA-V: Large Language Diffusion Models with Visual Instruction Tuning](https://mlsanity.com/paper/2505.16933/) (2025)
- [Derivative-Free Guidance in Continuous and Discrete Diffusion Models with Soft Value-Based Decoding](https://mlsanity.com/paper/2408.08252/) (2024)
- [Accelerated Sampling from Masked Diffusion Models via Entropy Bounded Unmasking](https://mlsanity.com/paper/2505.24857/) (2025)
- [Unlocking Guidance for Discrete State-Space Diffusion and Flow Models](https://mlsanity.com/paper/2406.01572/) (2024)
- [Consistency Flow Matching: Defining Straight Flows with Velocity Consistency](https://mlsanity.com/paper/2407.02398/) (2024)
- [Dimple: Discrete Diffusion Multimodal Large Language Model with Parallel Decoding](https://mlsanity.com/paper/2505.16990/) (2025)
- [Understanding Reinforcement Learning-Based Fine-Tuning of Diffusion Models: A Tutorial and Review](https://mlsanity.com/paper/2407.13734/) (2024)
- [Energy-Based Diffusion Language Models for Text Generation](https://mlsanity.com/paper/2410.21357/) (2024)
- [Inference-Time Alignment in Diffusion Models with Reward-Guided Generation: Tutorial and Review](https://mlsanity.com/paper/2501.09685/) (2025)
- [Variational Flow Matching for Graph Generation](https://mlsanity.com/paper/2406.04843/) (2024)
- [Path Planning for Masked Diffusion Model Sampling](https://mlsanity.com/paper/2502.03540/) (2025)
- [Fine-Tuning Discrete Diffusion Models via Reward Optimization with Applications to DNA and Protein Design](https://mlsanity.com/paper/2410.13643/) (2024)
- [All-atom Diffusion Transformers: Unified generative modelling of molecules and materials](https://mlsanity.com/paper/2503.03965/) (2025)
- [Fisher Flow Matching for Generative Modeling over Discrete Data](https://mlsanity.com/paper/2405.14664/) (2024)
- [Proteina: Scaling Flow-based Protein Structure Generative Models](https://mlsanity.com/paper/2503.00710/) (2025)
- [DPLM-2: A Multimodal Diffusion Protein Language Model](https://mlsanity.com/paper/2410.13782/) (2024)
- [Flow Matching with General Discrete Paths: A Kinetic-Optimal Perspective](https://mlsanity.com/paper/2412.03487/) (2024)
- [Edit Flows: Flow Matching with Edit Operations](https://mlsanity.com/paper/2506.09018/) (2025)
- [Mixed Continuous and Categorical Flow Matching for 3D De Novo Molecule Generation](https://mlsanity.com/paper/2404.19739/) (2024)
- [Generative Modeling of Molecular Dynamics Trajectories](https://mlsanity.com/paper/2409.17808/) (2024)
- [Any-Order Flexible Length Masked Diffusion](https://mlsanity.com/paper/2509.01025/) (2025)
- [How Discrete and Continuous Diffusion Meet: Comprehensive Analysis of Discrete Diffusion Models via a Stochastic Integral Framework](https://mlsanity.com/paper/2410.03601/) (2024)
- [Categorical Flow Matching on Statistical Manifolds](https://mlsanity.com/paper/2405.16441/) (2024)
- [Fast Solvers for Discrete Diffusion Models: Theory and Applications of High-Order Algorithms](https://mlsanity.com/paper/2502.00234/) (2025)
- [Theoretical Benefit and Limitation of Diffusion Language Model](https://mlsanity.com/paper/2502.09622/) (2025)

## Abstract (arXiv)

Combining discrete and continuous data is an important capability for generative models. We present Discrete Flow Models (DFMs), a new flow-based model of discrete data that provides the missing link in enabling flow-based generative models to be applied to multimodal continuous and discrete data problems. Our key insight is that the discrete equivalent of continuous space flow matching can be realized using Continuous Time Markov Chains. DFMs benefit from a simple derivation that includes discrete diffusion models as a specific instance while allowing improved performance over existing diffusion-based approaches. We utilize our DFMs method to build a multimodal flow-based modeling framework. We apply this capability to the task of protein co-design, wherein we learn a model for jointly generating protein structure and sequence. Our approach achieves state-of-the-art co-design performance while allowing the same multimodal model to be used for flexible generation of the sequence or structure.