分段生成再组装，设计出更优的蛋白质骨架
ProteinWeaver: A Divide-and-Assembly Approach for Protein Backbone Design
- 先生成蛋白结构域，再用SE(3)扩散模型灵活拼接
- 长链蛋白设计性能比RFdiffusion提升13%至39%
- 适合需要功能协同设计的蛋白质工程研究
自然界通过‘分而治之’策略构建多样蛋白。受此启发，我们提出ProteinWeaver，一种两阶段蛋白质骨架设计框架：首先生成独立蛋白结构域，再利用SE(3)扩散模型实现灵活组装。组装过程面临结构间相互作用景观复杂且崎岖的挑战，为此我们采用偏好对齐方法，通过对比生成样本分析结构与相互作用景观间的复杂关系。大量实验表明，ProteinWeaver能够通过多样的域组装生成高质量、新颖的蛋白质骨架；在长链蛋白设计上，相比当前最优方法RFdiffusion，分别提升13%和39%；并通过案例研究展示了协同功能设计的潜力。综上，ProteinWeaver引入‘分而治之’范式，推动蛋白质工程发展，为功能性蛋白设计开辟新路径。
原文摘要 · Abstract (English)
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.
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