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 par- tial redesign, providing a general and efficient platform for de novo protein design across diverse molecular targets.
id: green-raven-quartz

Multiple (2)
Strong (6)
True
16.2 kDa
151
id: bright-zebra-crystal

Nipah Virus Glycoprotein G
None
81.72
True
12.8 kDa
118
id: misty-lion-granite

Nipah Virus Glycoprotein G
None
87.78
True
12.6 kDa
118
id: violet-boar-stone

Nipah Virus Glycoprotein G
None
85.81
True
12.8 kDa
118
id: shy-moth-ash

Nipah Virus Glycoprotein G
None
86.45
True
16.2 kDa
151
id: young-gecko-topaz

Nipah Virus Glycoprotein G
None
86.46
True
16.0 kDa
157