Evidence map›Paper›PMID 41117072›Full record

ArticleAngewandte Chemie (International ed. in English)2025

De Novo Design of High-Affinity Miniprotein Binders Targeting Francisella Tularensis Virulence Factor.

Gizem Gokce-Alpkilic, Buwei Huang, Andi Liu, Lieselotte S M Kreuk, Yaxi Wang, Victor Adebomi, Yensi Flores Bueso, Asim K Bera, Alex Kang, Stacey R Gerben and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Angewandte Chemie (International ed. in English), 2025. 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. A scalable recombinant pipeline for disulphide-stapled peptides.bioRxiv : the preprint server for biology · 2026
    Article
  2. Materials today. Bio · 2026
    Article
  3. Orally available designed miniproteins inhibit enterotoxigenicbioRxiv : the preprint server for biology · 2026
    Article
  4. Review
  5. Article
  6. Article
  7. bioRxiv : the preprint server for biology · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Gizem Gokce-Alpkilic *Molecular Engineering and Sciences Institute, University of Washington, Seattle, WA, USA.ORCID 0000-0001-5009-4429
Buwei Huang *Institute for Protein Design, University of Washington, Seattle, WA, USA.
Andi LiuDepartment of Microbiology, University of Washington, Seattle, WA, USA.
Lieselotte S M KreukDepartment of Microbiology, University of Washington, Seattle, WA, USA.
Yaxi WangDepartment of Microbiology, University of Washington, Seattle, WA, USA.
Victor AdebomiDepartment of Medicinal Chemistry, University of Washington, Seattle, WA, USA.
Yensi Flores BuesoInstitute for Protein Design, University of Washington, Seattle, WA, USA.
Asim K BeraInstitute for Protein Design, University of Washington, Seattle, WA, USA.
Alex KangInstitute for Protein Design, University of Washington, Seattle, WA, USA.
Stacey R GerbenInstitute for Protein Design, University of Washington, Seattle, WA, USA.
Stephen RettieDepartment of Medicinal Chemistry, University of Washington, Seattle, WA, USA.
Dionne K VafeadosInstitute for Protein Design, University of Washington, Seattle, WA, USA.
Nicole RoullierInstitute for Protein Design, University of Washington, Seattle, WA, USA.
Inna GoreshnikInstitute for Protein Design, University of Washington, Seattle, WA, USA.
Xinting LiInstitute for Protein Design, University of Washington, Seattle, WA, USA.
David BakerInstitute for Protein Design, University of Washington, Seattle, WA, USA.
Joshua J WoodwardDepartment of Microbiology, University of Washington, Seattle, WA, USA.
Joseph D MougousDepartment of Microbiology, University of Washington, Seattle, WA, USA.
Gaurav BhardwajMolecular Engineering and Sciences Institute, University of Washington, Seattle, WA, USA.

Funding

X-ray Scattering Technology CoreP30GM133893 · NIGMS · BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB · PI Sean McSweeney · 2019 to 2026
$38.6M
De Novo Design of Minibinder Antagonists for COVID-19 and Future PandemicsR01AI160052 · NIAID · UNIVERSITY OF WASHINGTON · PI BAKER, DAVID, FULLER, DEBORAH H. · 2021 to 2025
$3.5M
DARPA Harnessing Enzymatic Activity for Lifesaving Remedies (HEALR) program HR001120S0052Marie Skłodowska-Curie Actions 101059124NIAID NIH HHS R01 AI160052NIGMS NIH HHS P30 GM133893NIH R01 R0AI160052The DOE Office of Biological and Environmental Research KP1607011The NIH-NIGMS through a Center Core P30 P30GM133893
6 · The paper itself

Abstract

Francisella tularensis poses considerable public health risk due to its high infectivity and potential for bioterrorism. Francisella-like lipoprotein (Flpp3), a key virulence factor unique to Francisella, plays critical roles in infection and immune evasion, making it a promising target for therapeutic development. However, the lack of well-defined binding pockets and structural information on native interactions has hindered structure-guided ligand discovery against Flpp3. Here, we used a combination of physics-based and deep-learning methods to design high-affinity miniprotein binders targeting two distinct sites on Flpp3. We identified four binders for site I with binding affinities ranging between 24-110 nM. For the second site, an initial binder showed a dissociation constant (K

Indexed as

Bacterial ProteinsFrancisella tularensisVirulence FactorsBinding SitesCrystallography, X-RayModels, MolecularBacterial ProteinsVirulence FactorsDeep learning‐guided designDe novo binder designHigh‑affinity protein bindersProtein engineeringProtein structure validation

Identifiers

PMID41117072
PMCPMC12723454

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.