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

Kavli Affiliate: Yi Zhou

| First 5 Authors: Yiming Ma, Fei Ye, Yi Zhou, Zaixiang Zheng, Dongyu Xue

| Summary:

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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