Evidence map›Paper›PMID 42026072›Full record

ArticleNature communications2026

In silico discovery of nanobody binders to a G-protein coupled receptor using AlphaFold-Multimer.

Edward P Harvey, Jeffrey S Smith, Joseph D Hurley, Alyana J Granados, Ernst W Schmid, Jason G Liang-Lin, Huyang Zhang, Emily M Meara, Elizabeth K Wren, Steffanie Paul and 7 more

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

  1. Article
  2. Review
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  8. Review
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

17 authors.

Edward P Harvey *Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Jeffrey S Smith *Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-2840-2899
Joseph D Hurley *Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-3903-318X
Alyana J GranadosDepartment of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA.
Ernst W SchmidDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-4662-5298
Jason G Liang-LinDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-4277-6694
Huyang ZhangDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Emily M MearaDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0009-0007-2643-8413
Elizabeth K WrenDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Steffanie PaulDepartment of Systems Biology, Harvard Medical School, Boston, MA, USA.
Matthew P FergusonDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0009-0004-9218-6283
Victor G Calvillo-MirandaDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0001-8631-4622
Miguel A AlcantarDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Debora S MarksDepartment of Systems Biology, Harvard Medical School, Boston, MA, USA.
Johannes C WalterDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-4186-7570
Andrew C KruseDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. Andrew_kruse@hms.harvard.edu.ORCID http://orcid.org/0000-0002-1467-1222
Katherine J SusaDepartment of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA. Katherine.Susa@ucsf.edu.ORCID http://orcid.org/0000-0003-0077-667X

Funding

The Fanconi anemia pathway: role in DNA interstrand cross-link repairR01HL098316 · NHLBI · HARVARD MEDICAL SCHOOL · PI Johannes Walter · 2010 to 2026
$6.3M
Identifying, Characterizing, and Targeting Regulators of B Cell ActivationDP5OD036136 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Katherine Julia Susa · 2023 to 2026
$1.6M
Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) DP5OD036136NHLBI NIH HHS R01 HL098316NIH HHS DP5 OD036136UC | UC San Francisco | UCSF Foundation Sandler Fellowship
6 · The paper itself

Abstract

Antibodies are central mediators of the adaptive immune response, and they are powerful research tools and therapeutics. Antibody discovery requires substantial experimental effort, such as immunization campaigns or in vitro library screening. Predicting antibody-antigen binding a priori remains challenging. However, recent machine learning methods raise the possibility of in silico antibody discovery, bypassing or reducing initial experimental bottlenecks. Here, we report a virtual screen using AlphaFold-Multimer (AF-M) that prospectively identified nanobody binders to MRGPRX2, a G protein-coupled receptor (GPCR) and therapeutic target for the treatment of pseudoallergic inflammation and itch. Using previously reported nanobody-GPCR structures, we identified a set of AF-M outputs that effectively discriminate between interacting and non-interacting nanobody-GPCR pairs. We used these outputs to perform a prospective in silico screen, identified nanobodies that bind MRGPRX2 with high affinity, and confirmed activity in signaling and functional cellular assays. Our results provide a proof of concept for fully computational antibody discovery pipelines that can circumvent laboratory experiments.

Indexed as

Nerve Tissue ProteinsReceptors, G-Protein-CoupledReceptors, NeuropeptideSingle-Domain AntibodiesAnimalsComputer SimulationHEK293 CellsHumansProtein BindingMRGPRX2 protein, humanNerve Tissue ProteinsReceptors, G-Protein-CoupledReceptors, NeuropeptideSingle-Domain Antibodies

Identifiers

PMID42026072
PMCPMC13315262

What OpenQuestion holds

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Registered trials

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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.