Evidence map›Paper›PMID 39071267›Full record

ArticlebioRxiv : the preprint server for biology2024

Diffusing protein binders to intrinsically disordered proteins.

Caixuan Liu, Kejia Wu, Hojun Choi, Hannah Han, Xulie Zhang, Joseph L Watson, Sara Shijo, Asim K Bera, Alex Kang, Evans Brackenbrough and 13 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors.

Caixuan LiuDepartment of Biochemistry, University of Washington, Seattle, WA, USA.ORCID 0000-0002-1954-0731
Kejia WuDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Hojun ChoiDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Hannah HanDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Xulie ZhangKey Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences Beijing, 100101, China.
Joseph L WatsonDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Sara ShijoDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, 98105, USA.
Asim K BeraDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Alex KangDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Evans BrackenbroughDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Brian CoventryDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Derrick R HickDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Andrew N HoofnagleDepartment of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, 98105, USA.
Ping ZhuKey Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences Beijing, 100101, China.
Xingting LiDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Justin DecarreauDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Stacey R GerbenDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Wei YangDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Xinru WangDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Mila LampDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Analisa MurrayDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Magnus BauerDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
David BakerDepartment of Biochemistry, University of Washington, Seattle, WA, USA.

Funding

X-ray Scattering Technology CoreP30GM133893 · BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB · 2025 to 2025
$4.6M
NIGMS NIH HHS P30 GM133893
6 · The paper itself

Abstract

Proteins which bind intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) with high affinity and specificity could have considerable utility for therapeutic and diagnostic applications. However, a general methodology for targeting IDPs/IDRs has yet to be developed. Here, we show that starting only from the target sequence of the input, and freely sampling both target and binding protein conformation, RFdiffusion can generate binders to IDPs and IDRs in a wide range of conformations. We use this approach to generate binders to the IDPs Amylin, C-peptide and VP48 in a range of conformations with Kds in the 3 -100nM range. The Amylin binder inhibits amyloid fibril formation and dissociates existing fibers, and enables enrichment of amylin for mass spectrometry-based detection. For the IDRs G3bp1, common gamma chain (IL2RG) and prion, we diffused binders to beta strand conformations of the targets, obtaining 10 to 100 nM affinity. The IL2RG binder colocalizes with the receptor in cells, enabling new approaches to modulating IL2 signaling. Our approach should be widely useful for creating binders to flexible IDPs/IDRs spanning a wide range of intrinsic conformational preferences.

Indexed as

Amyloid fibril dissociationdeep learningdiagnosticsIntrinsically disordered proteinintrinsically disordered regionprotein designRFdiffusionRosetta

Identifiers

PMID39071267
PMCPMC11275890

What Socratic holds

Textmetadata
LicenceCC BY-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.