ProteinWeaver: A Divide-and-Assembly Approach for Protein Backbone Design
This work addresses protein engineering for researchers, offering a novel paradigm that could enable functional protein design, though it is incremental in improving assembly methods.
The paper tackled the problem of designing novel protein backbones by introducing ProteinWeaver, a two-stage framework that generates domains and assembles them using an SE(3) diffusion model, resulting in outperforming RFdiffusion by 13% and 39% for long-chain proteins.
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.