# ProteinWeaver: A Divide-and-Assembly Approach for Protein Backbone Design

arXiv: https://arxiv.org/abs/2411.16686 · HTML: https://mlsanity.com/paper/2411.16686/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 11 of its 38 references that are in the map.
- First posted on arXiv 8 Nov 2024.

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

- [Adam: A Method for Stochastic Optimization](https://mlsanity.com/paper/1412.6980/) (2014)
- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [Score-Based Generative Modeling through Stochastic Differential Equations](https://mlsanity.com/paper/2011.13456/) (2020)
- [Generative Flows on Discrete State-Spaces: Enabling Multimodal Flows with Applications to Protein Co-Design](https://mlsanity.com/paper/2402.04997/) (2024)
- [Diffusion probabilistic modeling of protein backbones in 3D for the motif-scaffolding problem](https://mlsanity.com/paper/2206.04119/) (2022)
- [Self-Play Preference Optimization for Language Model Alignment](https://mlsanity.com/paper/2405.00675/) (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)
- [Protein structure generation via folding diffusion](https://mlsanity.com/paper/2209.15611/) (2022)
- [Generating Novel, Designable, and Diverse Protein Structures by Equivariantly Diffusing Oriented Residue Clouds](https://mlsanity.com/paper/2301.12485/) (2023)
- [Improved motif-scaffolding with SE(3) flow matching](https://mlsanity.com/paper/2401.04082/) (2024)

## Abstract (arXiv)

Nature creates diverse proteins through a 'divide and assembly' strategy. Inspired by this idea, we introduce ProteinWeaver, a two-stage framework for protein backbone design. Our method first generates individual protein domains and then employs an SE(3) diffusion model to flexibly assemble these domains. A key challenge lies in the assembling step, given the complex and rugged nature of the inter-domain interaction landscape. To address this challenge, we employ preference alignment to discern complex relationships between structure and interaction landscapes through comparative analysis of generated samples. Comprehensive experiments demonstrate that ProteinWeaver: (1) generates high-quality, novel protein backbones through versatile domain assembly; (2) outperforms RFdiffusion, the current state-of-the-art in backbone design, by 13% and 39% for long-chain proteins; (3) shows the potential for cooperative function design through illustrative case studies. To sum up, by introducing a `divide-and-assembly' paradigm, ProteinWeaver advances protein engineering and opens new avenues for functional protein design.