Evidence map›Paper›PMID 34773424›Full record

ArticleProteins2022

Functional antibody characterization via direct structural analysis and information-driven protein-protein docking.

Rafael S Depetris, Dan Lu, Zhanna Polonskaya, Zhikai Zhang, Xenia Luna, Amari Tankard, Pegah Kolahi, Michael Drummond, Chris Williams, Maximilian C C J C Ebert and 2 more

Open access · greenAbstract read
In one paragraph

Article in Proteins, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.7field-weighted citation impact, top 29% of its field
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

4 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Design of an Anti-HMGB1 Synthetic Antibody forJournal of the American Chemical Society · 2023
    Article
  3. Review
  4. 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

12 authors at 2 institutions in 2 countries.

Rafael S DepetrisKadmon Corporation, LLC, New York, New York, USA.ORCID 0000-0001-9707-6922
Dan LuKadmon Corporation, LLC, New York, New York, USA.
Zhanna PolonskayaKadmon Corporation, LLC, New York, New York, USA.
Zhikai ZhangKadmon Corporation, LLC, New York, New York, USA.
Xenia LunaKadmon Corporation, LLC, New York, New York, USA.
Amari TankardKadmon Corporation, LLC, New York, New York, USA.ORCID 0000-0003-3257-1652
Pegah KolahiKadmon Corporation, LLC, New York, New York, USA.
Michael DrummondChemical Computing Group, ULC, Montreal, Quebec, Canada.ORCID 0000-0002-4688-3975
Chris WilliamsChemical Computing Group, ULC, Montreal, Quebec, Canada.ORCID 0000-0001-5428-2742
Maximilian C C J C EbertChemical Computing Group, ULC, Montreal, Quebec, Canada.
Jeegar P PatelKadmon Corporation, LLC, New York, New York, USA.
Masha V PoyurovskyKadmon Corporation, LLC, New York, New York, USA.ORCID 0000-0002-3024-778X
Eon Corporation (United States) · USGroup for Research in Decision Analysis · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Detailed description of the mechanism of action of the therapeutic antibodies is essential for the functional characterization and future optimization of potential clinical agents. We recently developed KD035, a fully human antibody targeting vascular endothelial growth factor receptor 2 (VEGFR2). KD035 blocked VEGF-A, and VEGF-C-mediated VEGFR2 activation, as demonstrated by the in vitro binding and competition assays and functional cellular assays. Here, we report a computational model of the complex between the variable fragment of KD035 (KD035(Fv)) and the domains 2 and 3 of the extracellular portion of VEGFR2 (VEGFR2(D2-3)). Our modeling was guided by a priori experimental information including the X-ray structures of KD035 and related antibodies, binding assays, target domain mapping and comparison of KD035 affinity for VEGFR2 from different species. The accuracy of the model was assessed by molecular dynamics simulations, and subsequently validated by mutagenesis and binding analysis. Importantly, the steps followed during the generation of this model can set a precedent for future in silico efforts aimed at the accurate description of the antibody-antigen and more broadly protein-protein complexes.

Indexed as

AntibodiesVascular Endothelial Growth Factor AHumansMolecular Dynamics SimulationAntibodiesVascular Endothelial Growth Factor Aantibody-antigen modelingantibody X-ray structure functionmodel validation studiesmolecular dynamicsprotein complex modeling validationVEGFR2 clinical antibodyVEGF signaling

Identifiers

PMID34773424
PMCPMC9544432
OpenAlexW3214668463

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.