arXiv:2510.03095cs.LGcs.AI2025-10被引 1

用蒸馏技术让蛋白骨架生成快20倍,还保持高质量。

Distilled Protein Backbone Generation

  • 用分数蒸馏+多步生成与噪声调制,压缩采样步骤。
  • 生成速度提升20倍以上,设计度、多样性接近原模型。
  • 适合大规模虚拟蛋白设计,推动实际应用落地。

基于扩散和流的生成模型在蛋白质骨架生成任务中表现优异,具备前所未有的从头设计能力。然而,这些模型生成速度慢,逆向扩散过程通常需数百次迭代,限制了其在大规模蛋白发现中的实用性。为解决此问题,本文探索分数蒸馏技术,该技术已在视觉领域显著减少采样步骤并保持生成质量。但直接应用会导致设计度大幅下降。通过深入研究,我们成功将最先进的分数身份蒸馏(SiD)方法适配于蛋白骨架生成,训练出仅需少数几步即可生成的模型,显著降低采样时间,同时保持与预训练教师模型相当的性能。关键在于多步生成结合推理时噪声调制。实验表明,蒸馏后的少步生成器实现超过20倍的采样速度提升,且在设计度、多样性和新颖性方面与Proteina教师模型相当。这一效率提升使大规模体外蛋白设计成为可能,推动扩散模型更接近真实蛋白工程应用。PyTorch代码已开源:https://github.com/LY-Xie/SiD_Protein。

原文摘要 · Abstract (English)

Diffusion- and flow-based generative models have recently demonstrated strong performance in protein backbone generation tasks, offering unprecedented capabilities for de novo protein design. However, while achieving notable performance in generation quality, these models are limited by their generating speed, often requiring hundreds of iterative steps in the reverse-diffusion process. This computational bottleneck limits their practical utility in large-scale protein discovery, where thousands to millions of candidate structures are needed. To address this challenge, we explore the techniques of score distillation, which has shown great success in reducing the number of sampling steps in the vision domain while maintaining high generation quality. However, a straightforward adaptation of these methods results in unacceptably low designability. Through extensive study, we have identified how to appropriately adapt Score identity Distillation (SiD), a state-of-the-art score distillation strategy, to train few-step protein backbone generators which significantly reduce sampling time, while maintaining comparable performance to their pretrained teacher model. In particular, multistep generation combined with inference time noise modulation is key to the success. We demonstrate that our distilled few-step generators achieve more than a 20-fold improvement in sampling speed, while achieving similar levels of designability, diversity, and novelty as the Proteina teacher model. This reduction in inference cost enables large-scale in silico protein design, thereby bringing diffusion-based models closer to real-world protein engineering applications. The PyTorch implementation is available at https://github.com/LY-Xie/SiD_Protein

蛋白生成扩散模型蒸馏高效生成

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