mlsanityData to 7 Oct 2026

AlphaFold Meets Flow Matching for Generating Protein Ensembles

arXiv 2402.04845 ↗First posted 7 Feb 2024q-bio.BM cs.LGcited by 105

On the map: Diffusion models → Flow matching, time series and science

Abstract (arXiv)

The biological functions of proteins often depend on dynamic structural ensembles. In this work, we develop a flow-based generative modeling approach for learning and sampling the conformational landscapes of proteins. We repurpose highly accurate single-state predictors such as AlphaFold and ESMFold and fine-tune them under a custom flow matching framework to obtain sequence-conditoned generative models of protein structure called AlphaFlow and ESMFlow. When trained and evaluated on the PDB, our method provides a superior combination of precision and diversity compared to AlphaFold with MSA subsampling. When further trained on ensembles from all-atom MD, our method accurately captures conformational flexibility, positional distributions, and higher-order ensemble observables for unseen proteins. Moreover, our method can diversify a static PDB structure with faster wall-clock convergence to certain equilibrium properties than replicate MD trajectories, demonstrating its potential as a proxy for expensive physics-based simulations. Code is available at https://github.com/bjing2016/alphaflow.

Key facts. Cited by 105 papers in the map (data through 7 Oct 2026). Placed in Flow matching, time series and science, one of 14 directions in Diffusion models. Builds on 22 of its 66 references that are in the map. First posted on arXiv 7 Feb 2024.

Builds on

22 of 66 references.

Closest ancestors · 7

Same direction, newest first

  1. 2023SE(3)-Stochastic Flow Matching for Protein Backbone Generation3 Oct
  2. 2023Multisample Flow Matching: Straightening Flows with Minibatch Couplings28 Apr
  3. 2023EigenFold: Generative Protein Structure Prediction with Diffusion Models5 Apr
  4. 2023SE(3) diffusion model with application to protein backbone generation5 Feb
  5. 2023Two for One: Diffusion Models and Force Fields for Coarse-Grained Molecular Dynamics1 Feb
  6. 2022Flow Matching for Generative Modeling6 Oct
  7. 2022Flow Straight and Fast: Learning to Generate and Transfer Data with Rectified Flow7 Sep

Other references · 15

  1. 2020Denoising Diffusion Probabilistic Modelscited by 20,851
  2. 2021High-Resolution Image Synthesis with Latent Diffusion Modelscited by 18,694
  3. 2020Score-Based Generative Modeling through Stochastic Differential Equationscited by 8,964
  4. 2020Fourier Features Let Networks Learn High Frequency Functions in Low Dimensional Domainscited by 2,170
  5. 2023Consistency Modelscited by 1,778
  6. 2023One-step Diffusion with Distribution Matching Distillationcited by 978
  7. 2022Building Normalizing Flows with Stochastic Interpolantscited by 964
  8. 2023Stochastic Interpolants: A Unifying Framework for Flows and Diffusionscited by 897
  9. 2022Analog Bits: Generating Discrete Data using Diffusion Models with Self-Conditioningcited by 362
  10. 2022Flow Annealed Importance Sampling Bootstrapcited by 124
  11. 2021Smooth Normalizing Flowscited by 52
  12. 2023Harmonic Self-Conditioned Flow Matching for Multi-Ligand Docking and Binding Site Designcited by 29
3 more
  1. 2023Towards Predicting Equilibrium Distributions for Molecular Systems with Deep Learningcited by 26
  2. 2023Designing losses for data-free training of normalizing flows on Boltzmann distributionscited by 9
  3. 2023OpenProteinSet: Training data for structural biology at scalecited by 8

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Cited by year (2026 to 7 Oct)

Citing papers per year: 2024: 25; 2025: 48; 2026: 32.

105 papers.

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  1. 2024JanusFlow: Harmonizing Autoregression and Rectified Flow for Unified Multimodal Understanding and Generationcited by 162
  2. 2024Mixed Continuous and Categorical Flow Matching for 3D De Novo Molecule Generationcited by 53
  3. 2024Generative Modeling of Molecular Dynamics Trajectoriescited by 48
  4. 2025FUDOKI: Discrete Flow-based Unified Understanding and Generation via Kinetic-Optimal Velocitiescited by 46
  5. 2024Transferable Boltzmann Generatorscited by 43
  6. 2024ET-Flow: Equivariant Flow-Matching for Molecular Conformer Generationcited by 41
  7. 2024Sequence-Augmented SE(3)-Flow Matching For Conditional Protein Backbone Generationcited by 36
  8. 2025Scalable Equilibrium Sampling with Sequential Boltzmann Generatorscited by 36
  9. 2025Streaming Flow Policy: Simplifying diffusion/flow-matching policies by treating action trajectories as flow trajectoriescited by 34
  10. 2025Flow-Based Policy for Online Reinforcement Learningcited by 33
  11. 2024ActionFlow: Equivariant, Accurate, and Efficient Policies with Spatially Symmetric Flow Matchingcited by 25
  12. 2024ProteinBench: A Holistic Evaluation of Protein Foundation Modelscited by 23
38 more
  1. 2024FlowTS: Time Series Generation via Rectified Flowcited by 22
  2. 2025Action-Minimization Meets Generative Modeling: Efficient Transition Path Sampling with the Onsager-Machlup Functionalcited by 18
  3. 2025Solving Inverse Problems via Diffusion-Based Priors: An Approximation-Free Ensemble Sampling Approachcited by 18
  4. 2025Scalable Generation of Spatial Transcriptomics from Histology Images via Whole-Slide Flow Matchingcited by 18
  5. 2024Structure Language Models for Protein Conformation Generationcited by 16
  6. 2025SimpleFold: Folding Proteins is Simpler than You Thinkcited by 16
  7. 2024MOFFlow: Flow Matching for Structure Prediction of Metal-Organic Frameworkscited by 15
  8. 2025Offline Model-Based Optimization: Comprehensive Reviewcited by 14
  9. 2025Flow Matching Meets Biology and Life Science: A Surveycited by 14
  10. 2024RNAFlow: RNA Structure & Sequence Design via Inverse Folding-Based Flow Matchingcited by 12
  11. 2024Multi-Modal and Multi-Attribute Generation of Single Cells with CFGencited by 12
  12. 2026Enhanced Diffusion Sampling: Efficient Rare Event Sampling and Free Energy Calculation with Diffusion Modelscited by 11
  13. 2025dyAb: Flow Matching for Flexible Antibody Design with AlphaFold-driven Pre-binding Antigencited by 10
  14. 2025Elucidating the Design Space of Multimodal Protein Language Modelscited by 10
  15. 2025High-order Equivariant Flow Matching for Density Functional Theory Hamiltonian Predictioncited by 10
  16. 2026Improving Flow Matching by Aligning Flow Divergencecited by 9
  17. 2024Dynamic PDB: A New Dataset and a SE(3) Model Extension by Integrating Dynamic Behaviors and Physical Properties in Protein Structurescited by 8
  18. 2024FlowDock: Geometric Flow Matching for Generative Protein-Ligand Docking and Affinity Predictioncited by 8
  19. 2025Multiscale guidance of protein structure prediction with heterogeneous cryo-EM datacited by 8
  20. 2025Learning Boltzmann Generators via Constrained Mass Transportcited by 8
  21. 2025ConfRover: Simultaneous Modeling of Protein Conformation and Dynamics via Autoregressioncited by 7
  22. 2025BoltzNCE: Learning Likelihoods for Boltzmann Generation with Stochastic Interpolants and Noise Contrastive Estimationcited by 7
  23. 2025Unlocking hidden biomolecular conformational landscapes in diffusion models at inference timecited by 7
  24. 2025Hierarchical Rectified Flow Matching with Mini-Batch Couplingscited by 6
  25. 2025MD-LLM-1: A Large Language Model for Molecular Dynamicscited by 6
  26. 2025Accelerating Protein Molecular Dynamics Simulation with DeepJumpcited by 6
  27. 2025MarS-FM: Generative Modeling of Molecular Dynamics via Markov State Modelscited by 6
  28. 2024Boltzmann-Aligned Inverse Folding Model as a Predictor of Mutational Effects on Protein-Protein Interactionscited by 5
  29. 2025Aligning Protein Conformation Ensemble Generation with Physical Feedbackcited by 5
  30. 2025HollowFlow: Efficient Sample Likelihood Evaluation using Hollow Message Passingcited by 5
  31. 2024JAMUN: Bridging Smoothed Molecular Dynamics and Score-Based Learning for Conformational Ensemblescited by 4
  32. 2025Energy-Based Flow Matching for Generating 3D Molecular Structurecited by 4
  33. 2025Is There a Better Source Distribution than Gaussian? Exploring Source Distributions for Image Flow Matchingcited by 4
  34. 2026Scalable Spatio-Temporal SE(3) Diffusion for Long-Horizon Protein Dynamicscited by 4
  35. 2024AlphaFolding: 4D Diffusion for Dynamic Protein Structure Prediction with Reference and Motion Guidancecited by 3
  36. 2025Flow Matching Ergodic Coveragecited by 3
  37. 2025Learning residue level protein dynamics with multiscale Gaussianscited by 3
  38. 2025Diffusion Bridge or Flow Matching? A Unifying Framework and Comparative Analysiscited by 3

50 most cited of 105 All 105 (JSON)

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  1. 2024P2DFlow: A Protein Ensemble Generative Model with SE(3) Flow Matching
  2. 2025FlexiFlow: decomposable flow matching for generation of flexible molecular ensemble
  3. 2026Emyx: Fast and efficient all-atom protein generation
  4. 2026Few-step Cofolding with All-Atom Flow Maps
  5. 2025All-atom inverse protein folding through discrete flow matching
  6. 2025Let Physics Guide Your Protein Flows: Topology-aware Unfolding and Generation
  7. 2026Generative Modeling in Protein Design: Neural Representations, Conditional Generation, and Evaluation Standards
  8. 2026Active Flow Matching