# Full-Atom Peptide Design based on Multi-modal Flow Matching

arXiv: https://arxiv.org/abs/2406.00735 · HTML: https://mlsanity.com/paper/2406.00735/

## Key facts

- Cited by 34 papers in the map (data through 14 Oct 2026).
- Builds on 46 of its 122 references that are in the map.
- First posted on arXiv 2 Jun 2024.

## Builds on (most cited first, 30 of 46)

- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [Denoising Diffusion Implicit Models](https://mlsanity.com/paper/2010.02502/) (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)
- [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)
- [DPM-Solver: A Fast ODE Solver for Diffusion Probabilistic Model Sampling in Around 10 Steps](https://mlsanity.com/paper/2206.00927/) (2022)
- [Structured Denoising Diffusion Models in Discrete State-Spaces](https://mlsanity.com/paper/2107.03006/) (2021)
- [Building Normalizing Flows with Stochastic Interpolants](https://mlsanity.com/paper/2209.15571/) (2022)
- [Equivariant Diffusion for Molecule Generation in 3D](https://mlsanity.com/paper/2203.17003/) (2022)
- [Argmax Flows and Multinomial Diffusion: Learning Categorical Distributions](https://mlsanity.com/paper/2102.05379/) (2021)
- [GeoDiff: a Geometric Diffusion Model for Molecular Conformation Generation](https://mlsanity.com/paper/2203.02923/) (2022)
- [Learning from Protein Structure with Geometric Vector Perceptrons](https://mlsanity.com/paper/2009.01411/) (2020)
- [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)
- [SSD-LM: Semi-autoregressive Simplex-based Diffusion Language Model for Text Generation and Modular Control](https://mlsanity.com/paper/2210.17432/) (2022)
- [Pocket2Mol: Efficient Molecular Sampling Based on 3D Protein Pockets](https://mlsanity.com/paper/2205.07249/) (2022)
- [Biological Sequence Design with GFlowNets](https://mlsanity.com/paper/2203.04115/) (2022)
- [HIVE: Harnessing Human Feedback for Instructional Visual Editing](https://mlsanity.com/paper/2303.09618/) (2023)
- [ProGen2: Exploring the Boundaries of Protein Language Models](https://mlsanity.com/paper/2206.13517/) (2022)
- [Protein Design with Guided Discrete Diffusion](https://mlsanity.com/paper/2305.20009/) (2023)
- [SE(3)-Stochastic Flow Matching for Protein Backbone Generation](https://mlsanity.com/paper/2310.02391/) (2023)
- [A 3D Generative Model for Structure-Based Drug Design](https://mlsanity.com/paper/2203.10446/) (2022)
- [ProGen: Language Modeling for Protein Generation](https://mlsanity.com/paper/2004.03497/) (2020)
- [Riemannian Diffusion Models](https://mlsanity.com/paper/2208.07949/) (2022)
- [Protein structure generation via folding diffusion](https://mlsanity.com/paper/2209.15611/) (2022)
- [Accelerating Bayesian Optimization for Biological Sequence Design with Denoising Autoencoders](https://mlsanity.com/paper/2203.12742/) (2022)

## Built on by (most cited first, 30 of 34)

- [Training Free Guided Flow Matching with Optimal Control](https://mlsanity.com/paper/2410.18070/) (2024)
- [α-Flow: A Unified Framework for Continuous-State Discrete Flow Matching Models](https://mlsanity.com/paper/2504.10283/) (2025)
- [Flow Matching Meets Biology and Life Science: A Survey](https://mlsanity.com/paper/2507.17731/) (2025)
- [UniMoMo: Unified Generative Modeling of 3D Molecules for De Novo Binder Design](https://mlsanity.com/paper/2503.19300/) (2025)
- [An All-Atom Generative Model for Designing Protein Complexes](https://mlsanity.com/paper/2504.13075/) (2025)
- [Hotspot-Driven Peptide Design via Multi-Fragment Autoregressive Extension](https://mlsanity.com/paper/2411.18463/) (2024)
- [Riemannian Consistency Model](https://mlsanity.com/paper/2510.00983/) (2025)
- [Prior-Guided Flow Matching for Target-Aware Molecule Design with Learnable Atom Number](https://mlsanity.com/paper/2509.01486/) (2025)
- [Proteo-R1: Reasoning Foundation Models for De Novo Protein Design](https://mlsanity.com/paper/2605.02937/) (2026)
- [Molecular Representations in Implicit Functional Space via Hyper-Networks](https://mlsanity.com/paper/2601.22327/) (2026)
- [Zero-Shot Cyclic Peptide Design via Composable Geometric Constraints](https://mlsanity.com/paper/2507.04225/) (2025)
- [Quantum latent distributions in deep generative models](https://mlsanity.com/paper/2508.19857/) (2025)
- [ProteinAE: Protein Diffusion Autoencoders for Structure Encoding](https://mlsanity.com/paper/2510.10634/) (2025)
- [Surface-based Molecular Design with Multi-modal Flow Matching](https://mlsanity.com/paper/2601.04506/) (2026)
- [How well do generative models solve inverse problems? A benchmark study](https://mlsanity.com/paper/2601.23238/) (2026)
- [Rooted Absorbed Prefix Trajectory Balance with Submodular Replay for GFlowNet Training](https://mlsanity.com/paper/2603.00454/) (2026)
- [Integrating Protein Dynamics into Structure-Based Drug Design via Full-Atom Stochastic Flows](https://mlsanity.com/paper/2503.03989/) (2025)
- [Designing Cyclic Peptides via Harmonic SDE with Atom-Bond Modeling](https://mlsanity.com/paper/2505.21452/) (2025)
- [AffinityFlow: Guided Flows for Antibody Affinity Maturation](https://mlsanity.com/paper/2502.10365/) (2025)
- [Full-Atom Peptide Design via Riemannian-Euclidean Bayesian Flow Networks](https://mlsanity.com/paper/2511.14516/) (2025)
- [APCyc: Property-Informed Design of Cyclic Peptides via Automated Cyclization](https://mlsanity.com/paper/2606.12991/) (2026)
- [Variable-Length Generative Protein Design via Generalized Poisson Flow](https://mlsanity.com/paper/2607.09039/) (2026)
- [Computational design of target-specific linear peptide binders with TransformerBeta](https://mlsanity.com/paper/2410.16302/) (2024)
- [THFlow: A Temporally Hierarchical Flow Matching Framework for 3D Peptide Design](https://mlsanity.com/paper/2502.15855/) (2025)
- [BindEnergyCraft: Casting Protein Structure Predictors as Energy-Based Models for Binder Design](https://mlsanity.com/paper/2505.21241/) (2025)
- [NS-Pep: De novo Peptide Design with Non-Standard Amino Acids](https://mlsanity.com/paper/2510.03326/) (2025)
- [Latent Retrieval Augmented Generation of Cross-Domain Protein Binders](https://mlsanity.com/paper/2510.10480/) (2025)
- [Joint Design of Protein Surface and Structure Using a Diffusion Bridge Model](https://mlsanity.com/paper/2511.16675/) (2025)
- [Generative design and validation of therapeutic peptides for glioblastoma based on a potential target ATP5A](https://mlsanity.com/paper/2512.02030/) (2025)
- [Cross-Chirality Generalization by Axial Vectors for Hetero-Chiral Protein-Peptide Interaction Design](https://mlsanity.com/paper/2602.20176/) (2026)

## Abstract (arXiv)

Peptides, short chains of amino acid residues, play a vital role in numerous biological processes by interacting with other target molecules, offering substantial potential in drug discovery. In this work, we present PepFlow, the first multi-modal deep generative model grounded in the flow-matching framework for the design of full-atom peptides that target specific protein receptors. Drawing inspiration from the crucial roles of residue backbone orientations and side-chain dynamics in protein-peptide interactions, we characterize the peptide structure using rigid backbone frames within the SE(3) manifold and side-chain angles on high-dimensional tori. Furthermore, we represent discrete residue types in the peptide sequence as categorical distributions on the probability simplex. By learning the joint distributions of each modality using derived flows and vector fields on corresponding manifolds, our method excels in the fine-grained design of full-atom peptides. Harnessing the multi-modal paradigm, our approach adeptly tackles various tasks such as fix-backbone sequence design and side-chain packing through partial sampling. Through meticulously crafted experiments, we demonstrate that PepFlow exhibits superior performance in comprehensive benchmarks, highlighting its significant potential in computational peptide design and analysis.