# Protein generation with embedding learning for motif diversification

arXiv: https://arxiv.org/abs/2510.18790 · HTML: https://mlsanity.com/paper/2510.18790/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 11 of its 49 references that are in the map.
- First posted on arXiv 21 Oct 2025.

## Builds on (most cited first, 11 of 11)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [High-Resolution Image Synthesis with Latent Diffusion Models](https://mlsanity.com/paper/2112.10752/) (2021)
- [An Image is Worth One Word: Personalizing Text-to-Image Generation using Textual Inversion](https://mlsanity.com/paper/2208.01618/) (2022)
- [Diffusion probabilistic modeling of protein backbones in 3D for the motif-scaffolding problem](https://mlsanity.com/paper/2206.04119/) (2022)
- [Practical and Asymptotically Exact Conditional Sampling in Diffusion Models](https://mlsanity.com/paper/2306.17775/) (2023)
- [Protein structure generation via folding diffusion](https://mlsanity.com/paper/2209.15611/) (2022)
- [Learning protein sequence embeddings using information from structure](https://mlsanity.com/paper/1902.08661/) (2019)
- [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)
- [What is a meaningful representation of protein sequences?](https://mlsanity.com/paper/2012.02679/) (2020)
- [An Image is Worth Multiple Words: Discovering Object Level Concepts using Multi-Concept Prompt Learning](https://mlsanity.com/paper/2310.12274/) (2023)

## Abstract (arXiv)

A fundamental challenge in protein design is the trade-off between generating structural diversity while preserving motif biological function. Current state-of-the-art methods, such as partial diffusion in RFdiffusion, often fail to resolve this trade-off: small perturbations yield motifs nearly identical to the native structure, whereas larger perturbations violate the geometric constraints necessary for biological function. We introduce Protein Generation with Embedding Learning (PGEL), a general framework that learns high-dimensional embeddings encoding sequence and structural features of a target motif in the representation space of a diffusion model's frozen denoiser, and then enhances motif diversity by introducing controlled perturbations in the embedding space. PGEL is thus able to loosen geometric constraints while satisfying typical design metrics, leading to more diverse yet viable structures. We demonstrate PGEL on three representative cases: a monomer, a protein-protein interface, and a cancer-related transcription factor complex. In all cases, PGEL achieves greater structural diversity, better designability, and improved self-consistency, as compared to partial diffusion. Our results establish PGEL as a general strategy for embedding-driven protein generation allowing for systematic, viable diversification of functional motifs.