mlsanityData to 7 Oct 2026

Improved motif-scaffolding with SE(3) flow matching

arXiv 2401.04082 ↗First posted 8 Jan 2024q-bio.QM cs.LG stat.MLcited by 43

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Abstract (arXiv)

Protein design often begins with the knowledge of a desired function from a motif which motif-scaffolding aims to construct a functional protein around. Recently, generative models have achieved breakthrough success in designing scaffolds for a range of motifs. However, generated scaffolds tend to lack structural diversity, which can hinder success in wet-lab validation. In this work, we extend FrameFlow, an SE(3) flow matching model for protein backbone generation, to perform motif-scaffolding with two complementary approaches. The first is motif amortization, in which FrameFlow is trained with the motif as input using a data augmentation strategy. The second is motif guidance, which performs scaffolding using an estimate of the conditional score from FrameFlow without additional training. On a benchmark of 24 biologically meaningful motifs, we show our method achieves 2.5 times more designable and unique motif-scaffolds compared to state-of-the-art. Code: https://github.com/microsoft/protein-frame-flow

Key facts. Cited by 43 papers in the map (data through 7 Oct 2026). Builds on 21 of its 51 references that are in the map. First posted on arXiv 8 Jan 2024.

Builds on

21 of 51 references.

References · 21

  1. 2017Attention Is All You Needcited by 59,932
  2. 2019PyTorch: An Imperative Style, High-Performance Deep Learning Librarycited by 20,160
  3. 2020Score-Based Generative Modeling through Stochastic Differential Equationscited by 8,964
  4. 2022Classifier-Free Diffusion Guidancecited by 5,717
  5. 2022Flow Matching for Generative Modelingcited by 5,426
  6. 2018Neural Ordinary Differential Equationscited by 3,733
  7. 2022Diffusion Posterior Sampling for General Noisy Inverse Problemscited by 1,375
  8. 2021Palette: Image-to-Image Diffusion Modelscited by 1,296
  9. 2021Solving Inverse Problems in Medical Imaging with Score-Based Generative Modelscited by 514
  10. 2020Equivariant Flows: Exact Likelihood Generative Learning for Symmetric Densitiescited by 248
  11. 2022Diffusion probabilistic modeling of protein backbones in 3D for the motif-scaffolding problemcited by 229
  12. 2023Practical and Asymptotically Exact Conditional Sampling in Diffusion Modelscited by 218
9 more
  1. 2023SE(3) diffusion model with application to protein backbone generationcited by 214
  2. 2023Flow Matching in Latent Spacecited by 155
  3. 2023SE(3)-Stochastic Flow Matching for Protein Backbone Generationcited by 147
  4. 2023Equivariant flow matchingcited by 131
  5. 2023Guided Flows for Generative Modeling and Decision Makingcited by 99
  6. 2023Stochastic interpolants with data-dependent couplingscited by 94
  7. 2023Training-free Linear Image Inverses via Flowscited by 70
  8. 2023On Kinetic Optimal Probability Paths for Generative Modelscited by 42
  9. 2023A framework for conditional diffusion modelling with applications in motif scaffolding for protein designcited by 22

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Cited by year (2026 to 7 Oct)

Citing papers per year: 2024: 16; 2025: 23; 2026: 4.

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  1. 2025Proteina: Scaling Flow-based Protein Structure Generative Modelscited by 63
  2. 2024DPLM-2: A Multimodal Diffusion Protein Language Modelcited by 59
  3. 2024Sequence-Augmented SE(3)-Flow Matching For Conditional Protein Backbone Generationcited by 36
  4. 2024The Superposition of Diffusion Models Using the Ito Density Estimatorcited by 36
  5. 2024Full-Atom Peptide Design based on Multi-modal Flow Matchingcited by 34
  6. 2024Out of Many, One: Designing and Scaffolding Proteins at the Scale of the Structural Universe with Genie 2cited by 33
  7. 2025La-Proteina: Atomistic Protein Generation via Partially Latent Flow Matchingcited by 26
  8. 2024ProteinBench: A Holistic Evaluation of Protein Foundation Modelscited by 23
  9. 2024Training Free Guided Flow Matching with Optimal Controlcited by 23
  10. 2024Trivialized Momentum Facilitates Diffusion Generative Modeling on Lie Groupscited by 19
  11. 2024MOFFlow: Flow Matching for Structure Prediction of Metal-Organic Frameworkscited by 15
  12. 2025Flow Matching Meets Biology and Life Science: A Surveycited by 14
31 more
  1. 2024Extended Flow Matching: a Method of Conditional Generation with Generalized Continuity Equationcited by 11
  2. 2024Diffusion on language model encodings for protein sequence generationcited by 11
  3. 2025Elucidating the Design Space of Multimodal Protein Language Modelscited by 10
  4. 2025High-order Equivariant Flow Matching for Density Functional Theory Hamiltonian Predictioncited by 10
  5. 2024Hotspot-Driven Peptide Design via Multi-Fragment Autoregressive Extensioncited by 9
  6. 2025An All-Atom Generative Model for Designing Protein Complexescited by 9
  7. 2025Flexible MOF Generation with Torsion-Aware Flow Matchingcited by 9
  8. 2024Generating Highly Designable Proteins with Geometric Algebra Flow Matchingcited by 7
  9. 2025Chance-constrained Flow Matching for High-Fidelity Constraint-aware Generationcited by 7
  10. 2024Secondary Structure-Guided Novel Protein Sequence Generation with Latent Graph Diffusioncited by 5
  11. 2025Protein Design with Dynamic Protein Vocabularycited by 5
  12. 2026Riemannian MeanFlowcited by 5
  13. 2025ProtFlow: Fast Protein Sequence Design via Flow Matching on Compressed Protein Language Model Embeddingscited by 4
  14. 2025ProxelGen: Generating Proteins as 3D Densitiescited by 4
  15. 2025HD-Prot: A Protein Language Model for Joint Sequence-Structure Modeling with Continuous Structure Tokenscited by 4
  16. 2025PolyConf: Unlocking Polymer Conformation Generation through Hierarchical Generative Modelscited by 3
  17. 2025Integrating Protein Dynamics into Structure-Based Drug Design via Full-Atom Stochastic Flowscited by 2
  18. 2025Designing Cyclic Peptides via Harmonic SDE with Atom-Bond Modelingcited by 2
  19. 2025Flexibility-Conditioned Protein Structure Design with Flow Matchingcited by 2
  20. 2025Monte Carlo Tree Diffusion with Multiple Experts for Protein Designcited by 2
  21. 2024Efficient Antibody Structure Refinement Using Energy-Guided SE(3) Flow Matchingcited by 1
  22. 2025MotifBench: A standardized protein design benchmark for motif-scaffolding problemscited by 1
  23. 2025Learning conformational ensembles of proteins based on backbone geometrycited by 1
  24. 2025Flash Invariant Point Attentioncited by 1
  25. 2025Sesame: Opening the door to protein pocketscited by 1
  26. 2025EnzyControl: Adding Functional and Substrate-Specific Control for Enzyme Backbone Generationcited by 1
  27. 2026Generative Modeling in Protein Design: Neural Representations, Conditional Generation, and Evaluation Standardscited by 1
  28. 2024ProteinWeaver: A Divide-and-Assembly Approach for Protein Backbone Designcited by 0
  29. 2025Matching the Optimal Denoiser in Point Cloud Diffusion with (Improved) Rotational Alignmentcited by 0
  30. 2026Unlocking Multimodal Protein Language Models at Inference Timecited by 0
  31. 2026Correcting the Dropout-LayerNorm Expectation Gap Improves Protein Structure Modelscited by 0

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  2. 2025Flows, straight but not so fast: Exploring the design space of Rectified Flows in Protein Design
  3. 2026ProHiFlo: Hierarchical Flow Matching with Functional Guidance for De Novo Protein Generation
  4. 2026SE(3)-MeanFlow: Few-Step Protein Backbone Generation on Lie Groups
  5. 2025SPID: Distilled Protein Backbone Generation
  6. 2025Protein generation with embedding learning for motif diversification
  7. 2024On diffusion posterior sampling via sequential Monte Carlo for zero-shot scaffolding of protein motifs
  8. 2025Energy-Based Flow Matching for Generating 3D Molecular Structure