Evidence map›Paper›PMID 40686280›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

A Complementarity-Based Approach to De Novo Binder Design.

Kateryna Maksymenko, Valeriia Hatskovska, Murray Coles, Narges Aghaallaei, Natalia Pashkovskaia, Natalia Borbarán-Bravo, Matteo Pilz, Philip Bucher, Mareike Volz, Joana Pereira and 8 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. A Complementarity-Based Approach to De Novo Binder Design.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Kateryna MaksymenkoDepartment of Protein Evolution, Max Planck Institute for Biology, 72076, Tübingen, Germany.
Valeriia HatskovskaDepartment of Protein Evolution, Max Planck Institute for Biology, 72076, Tübingen, Germany.
Murray ColesDepartment of Protein Evolution, Max Planck Institute for Biology, 72076, Tübingen, Germany.
Narges AghaallaeiDivision of Translational Oncology, University Hospital Tübingen, 72076, Tübingen, Germany.
Natalia PashkovskaiaInstitute of Neuroanatomy and Developmental Biology, Eberhard Karls University Tübingen, 72074, Tübingen, Germany.
Natalia Borbarán-BravoDivision of Translational Oncology, University Hospital Tübingen, 72076, Tübingen, Germany.
Matteo PilzApplied Bioinformatics, Department of Computer Science, Eberhard Karls University Tübingen, 72076, Tübingen, Germany.
Philip BucherCluster of Excellence iFIT (EXC2180) "Image-guided and Functionally Instructed Tumor Therapies", Eberhard Karls University Tübingen, 72076, Tübingen, Germany.
Mareike VolzInstitute of Neuroanatomy and Developmental Biology, Eberhard Karls University Tübingen, 72074, Tübingen, Germany.
Joana PereiraDepartment of Protein Evolution, Max Planck Institute for Biology, 72076, Tübingen, Germany.
Marcus D HartmannDepartment of Protein Evolution, Max Planck Institute for Biology, 72076, Tübingen, Germany.
Ghazaleh TabatabaiCluster of Excellence iFIT (EXC2180) "Image-guided and Functionally Instructed Tumor Therapies", Eberhard Karls University Tübingen, 72076, Tübingen, Germany.
Judith FeuchtCluster of Excellence iFIT (EXC2180) "Image-guided and Functionally Instructed Tumor Therapies", Eberhard Karls University Tübingen, 72076, Tübingen, Germany.
Stefan LiebauInstitute of Neuroanatomy and Developmental Biology, Eberhard Karls University Tübingen, 72074, Tübingen, Germany.
Patrick MüllerFriedrich Miescher Laboratory of the Max Planck Society, 72076, Tübingen, Germany.
Andrei N LupasDepartment of Protein Evolution, Max Planck Institute for Biology, 72076, Tübingen, Germany.
Julia SkokowaDivision of Translational Oncology, University Hospital Tübingen, 72076, Tübingen, Germany.
Mohammad ElGamacyDepartment of Protein Evolution, Max Planck Institute for Biology, 72076, Tübingen, Germany.ORCID https://orcid.org/0000-0002-3446-8774

Funding

Deutsche Forschungsgemeinschaft 500215849Fortüne program of the University of Tübingen 2667-0-0HORIZON EUROPE European Research Council No 863952José Carreras Leukämie-Stiftung DJCLS 10 R/2024Max-Planck-GesellschaftM. Schickedanz Kinderkrebsstiftung
6 · The paper itself

Abstract

De novo design of binders capable of targeting arbitrarily selected epitopes remains a substantial challenge. Here, a generalizable computational strategy is presented to design site-specific protein binders, obviating steps of extensive empirical optimization or in vitro screening. The dock-and-design pipeline retrieves complementary scaffolds from a protein structure database to a given query epitope, where the scaffold is mutated to carve a binding site de novo. The docking step utilizes a novel fingerprint that greatly simplifies and accelerates the surface complementarity evaluation. As proof-of-concept, we designed protein binders to target three distinct epitopes on two different oncogenic targets; vascular endothelial growth factor (VEGF) and interleukin-7 receptor-α (IL-7Rα). Experimental characterization of only 24 candidates identified nanomolar binders against each of the target epitopes, where the binders belonged to five different folds. Several designs were active in vitro. Moreover, anti-VEGF designs showed tumor-inhibiting activity in vivo, highlighting their therapeutic potential.

Indexed as

Drug DesignEpitopesVascular Endothelial Growth Factor AAnimalsBinding SitesHumansMiceMolecular Docking SimulationProtein BindingEpitopesVascular Endothelial Growth Factor Acomplementarity evaluationde novo binder designIL‐7R bindersprotein‐protein dockingVEGF inhibitors

Identifiers

PMID40686280
PMCPMC12412469

What OpenQuestion holds

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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 OpenQuestion graph.