# ProteinAE: Protein Diffusion Autoencoders for Structure Encoding

arXiv: https://arxiv.org/abs/2510.10634 · HTML: https://mlsanity.com/paper/2510.10634/

## Key facts

- Cited by 3 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 28 of its 44 references that are in the map.
- First posted on arXiv 12 Oct 2025.

## 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, 28 of 28)

- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [U-Net: Convolutional Networks for Biomedical Image Segmentation](https://mlsanity.com/paper/1505.04597/) (2015)
- [High-Resolution Image Synthesis with Latent Diffusion Models](https://mlsanity.com/paper/2112.10752/) (2021)
- [Deep Unsupervised Learning using Nonequilibrium Thermodynamics](https://mlsanity.com/paper/1503.03585/) (2015)
- [Scalable Diffusion Models with Transformers](https://mlsanity.com/paper/2212.09748/) (2022)
- [Flow Matching for Generative Modeling](https://mlsanity.com/paper/2210.02747/) (2022)
- [RoFormer: Enhanced Transformer with Rotary Position Embedding](https://mlsanity.com/paper/2104.09864/) (2021)
- [Flow Straight and Fast: Learning to Generate and Transfer Data with Rectified Flow](https://mlsanity.com/paper/2209.03003/) (2022)
- [Taming Transformers for High-Resolution Image Synthesis](https://mlsanity.com/paper/2012.09841/) (2020)
- [Structured Denoising Diffusion Models in Discrete State-Spaces](https://mlsanity.com/paper/2107.03006/) (2021)
- [Stochastic Interpolants: A Unifying Framework for Flows and Diffusions](https://mlsanity.com/paper/2303.08797/) (2023)
- [Vision Transformers Need Registers](https://mlsanity.com/paper/2309.16588/) (2023)
- [Generative Flows on Discrete State-Spaces: Enabling Multimodal Flows with Applications to Protein Co-Design](https://mlsanity.com/paper/2402.04997/) (2024)
- [SE(3) diffusion model with application to protein backbone generation](https://mlsanity.com/paper/2302.02277/) (2023)
- [SE(3)-Stochastic Flow Matching for Protein Backbone Generation](https://mlsanity.com/paper/2310.02391/) (2023)
- [FlexTok: Resampling Images into 1D Token Sequences of Flexible Length](https://mlsanity.com/paper/2502.13967/) (2025)
- [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)
- [Categorical Flow Matching on Statistical Manifolds](https://mlsanity.com/paper/2405.16441/) (2024)
- [Sequence-Augmented SE(3)-Flow Matching For Conditional Protein Backbone Generation](https://mlsanity.com/paper/2405.20313/) (2024)
- [Out of Many, One: Designing and Scaffolding Proteins at the Scale of the Structural Universe with Genie 2](https://mlsanity.com/paper/2405.15489/) (2024)
- [Full-Atom Peptide Design based on Multi-modal Flow Matching](https://mlsanity.com/paper/2406.00735/) (2024)
- [A Latent Diffusion Model for Protein Structure Generation](https://mlsanity.com/paper/2305.04120/) (2023)
- [Diffusion Autoencoders are Scalable Image Tokenizers](https://mlsanity.com/paper/2501.18593/) (2025)
- [What is a meaningful representation of protein sequences?](https://mlsanity.com/paper/2012.02679/) (2020)
- [Protein Structure Tokenization: Benchmarking and New Recipe](https://mlsanity.com/paper/2503.00089/) (2025)
- [Elucidating the Design Space of Multimodal Protein Language Models](https://mlsanity.com/paper/2504.11454/) (2025)
- [MSAGPT: Neural Prompting Protein Structure Prediction via MSA Generative Pre-Training](https://mlsanity.com/paper/2406.05347/) (2024)

## Built on by (most cited first, 3 of 3)

- [NNiT: Width-Agnostic Neural Network Generation with Structurally Aligned Weight Spaces](https://mlsanity.com/paper/2603.00180/) (2026)
- [SinAE: A Single-Architecture Flow-Matching Autoencoder for Cross-Domain Atomic Systems](https://mlsanity.com/paper/2607.12380/) (2026)
- [Flow-Matching-Based Protein Structure Tokenizer Made Efficient and Easy](https://mlsanity.com/paper/2609.33129/) (2026)

## Abstract (arXiv)

Developing effective representations of protein structures is essential for advancing protein science, particularly for protein generative modeling. Current approaches often grapple with the complexities of the SE(3) manifold, rely on discrete tokenization, or the need for multiple training objectives, all of which can hinder the model optimization and generalization. We introduce ProteinAE, a novel and streamlined protein diffusion autoencoder designed to overcome these challenges by directly mapping protein backbone coordinates from E(3) into a continuous, compact latent space. ProteinAE employs a non-equivariant Diffusion Transformer with a bottleneck design for efficient compression and is trained end-to-end with a single flow matching objective, substantially simplifying the optimization pipeline. We demonstrate that ProteinAE achieves state-of-the-art reconstruction quality, outperforming existing autoencoders. The resulting latent space serves as a powerful foundation for a latent diffusion model that bypasses the need for explicit equivariance. This enables efficient, high-quality structure generation that is competitive with leading structure-based approaches and significantly outperforms prior latent-based methods. Code is available at https://github.com/OnlyLoveKFC/ProteinAE_v1.