Evidence map›Paper›PMID 41819089›Full record

ArticleCell chemical biology2026

De novo design of Ras isoform selective binders.

Jason Z Zhang, Xinting Li, Alexa Rane Batingana, Caixuan Liu, Hanlun Jiang, Kevin Shannon, Benjamin J Huang, Kejia Wu, David Baker

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell chemical biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
  2. Review
  3. Beyond evolution:Biosafety and health · 2025
    Review
  4. bioRxiv : the preprint server for biology · 2025
    Article
  5. Article
  6. Article
  7. Recent progress and future challenges in structure-based protein-protein interaction prediction.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
4 · The record

Corrections and comments

  • Update of
    2025
5 · Who and what money

Authors and funding

9 authors.

Jason Z ZhangDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA; Biological Physics, Structure and Design Graduate Program, University of Washington, Seattle, WA 98195, USA. Electronic address: jzz0428@g.ucla.edu.
Xinting LiDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Alexa Rane BatinganaDepartment of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA.
Caixuan LiuDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
Hanlun JiangDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Department of Electrical Engineering and Computer Science, University of California, Berkeley, Berkeley, CA 94720, USA.
Kevin ShannonDepartment of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Benjamin J HuangDepartment of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Kejia WuDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Biological Physics, Structure and Design Graduate Program, University of Washington, Seattle, WA 98195, USA. Electronic address: kejiawu@uw.edu.
David BakerDepartment of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA. Electronic address: dabaker@uw.edu.

Funding

Selectively Targeting Oncogenic NRAS in CancerR01CA193994 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KEVIN M. SHANNON · 2015 to 2026
$5.8M
Co-targeting BET Bromodomain Proteins and Aberrant Signaling in AML.K08CA256489 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HUANG, BENJAMIN · 2021 to 2025
$1.2M
De novo designed Ras tools to uncover the mechanisms underlying drug resistanceR00CA293001 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Jason Zhang · 2025 to 2026
$570k
NCI NIH HHS K08 CA256489NCI NIH HHS R00 CA293001NCI NIH HHS R01 CA193994
6 · The paper itself

Abstract

The four major isoforms encoded by RAS proto-oncogenes are differentially associated with cancer, but there are few isoform-specific binding reagents becasue the sequence differences are confined to their disordered C termini. To overcome this limitation, we use deep learning-based methods to design Ras isoform-specific binders (RIBs) for all major Ras isoforms de novo by targeting the Ras C terminus. The RIBs bind to their target Ras isoforms both in vitro and in cells with remarkable specificity, disrupting their membrane localization and inhibiting Ras activity. The RIBs enable dissection of the distinct roles of Ras isoforms during Ras

Indexed as

Drug Designras ProteinsHumansProtein BindingProtein IsoformsProtein Isoformsras Proteinscancerintrinsically disordered regionsprotein designprotein engineeringRAS

Identifiers

PMID41819089
PMCPMC12982892

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

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.