尹志 (2025-11-30 19:01):
#paper doi: 10.1101/2025.10.10.681530 Protein Hunter: exploiting structure hallucination within diffusion for protein design。基于生成式AI的蛋白质设计已经成为一种卓有成效的计算范式,但现在大多数的诟病来源于它的准确稳定及泛化能力。我非常认同本文提出的观点,即不需要对生成式AI蛋白质设计“要求过高”,即使存在幻觉,那么幻觉本身就是一种自洽的模式。我们可以通过某些特定的metric去筛选由幻觉产生的结果。考虑到当前已经有很多优秀的模型对蛋白质本身的规律(规律子集)有很好的描述,那么将这样的模型改造为生成器,通过其它手段去进行筛选,可以更充分的利用现有的大量模型。
Protein Hunter: exploiting structure hallucination within diffusion for protein design
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Abstract:
1 Abstract Interactions between proteins and other biomolecules underlie nearly all biological processes, yet designing such interactions de novo remains challenging. Capturing their specific interactions and co-optimizing sequence and structure are difficult and often require extensive computation. We present Protein Hunter, a fast, fine-tuning-free framework for de novo protein design. Starting from an all-X sequence, we find diffusion-based structure prediction models hallucinate reasonable looking structures that can be further improved through iterative sequence re-design and structure re-prediction. This lightweight strategy achieves high AlphaFold3 in silico success rates across both unconditional and conditional generation tasks, including binders to proteins, cyclic peptides, small molecules, DNA, and RNA. Protein Hunter also supports multi-motif scaffolding and partial redesign, providing a general and efficient platform for de novo protein design across diverse molecular targets.
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