A computer screen finds antibody fragments for an itch receptor

Harvard and UCSF researchers co-folded 10,000 nanobodies with MRGPRX2 in AlphaFold-Multimer; of ten tested, three bound at 20 to 200 nM and blocked mast cell degranulation.

2
Benefit status
Reported
Evidence
Claimed by the parties
Source published
Sources
1 publication
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Benefits

Benefit

Bound MRGPRX2 with affinities between about 20 and 200 nM

Awaiting review

Outcome identifiers

Unresolved

Not reviewedUnresolved

Category

Improved Knowledge Discovery

Awaiting review

Status

Reported benefit

Awaiting review

Beneficiary groups

Society.

Awaiting review

Beneficiaries

Unresolved

Not reviewedUnresolved

Reach

Unresolved

Not reviewedUnresolved

Distribution and access

Unresolved

Not reviewedUnresolved

Duration

Unresolved

Not reviewedUnresolved

Expected?

Yes

Awaiting review

Costs and harms

Unresolved

Not reviewedUnresolved

AI system

System

AlphaFold-Multimer (AF-M), run through a modified ColabFold script

Awaiting review

Model

This is an explicit unresolved assignment: the sources on record do not settle this question.

Not reviewedUnresolved

Release

Unresolved

Not reviewedUnresolved

Provider

Unresolved

Not reviewedUnresolved

Role

Unresolved

Not reviewedUnresolved

Configuration

Unresolved

Not reviewedUnresolved

Inputs and outputs

Unresolved

Not reviewedUnresolved

Autonomy

Unresolved

Not reviewedUnresolved

Workflow

The team checked that the confidence metric separated known binders from non-binders. Ten top-ranked nanobodies were made and tested.

Awaiting review

Human oversight

Unresolved

Not reviewedUnresolved

Relation to AI

The authors tested only AlphaFold-Multimer picks; they had no arm with randomly chosen or experimentally screened nanobodies.

Awaiting review

AI contribution

Unresolved

Not reviewedUnresolved

Measurement

Studies

Other. [1]

Fully reviewed

Review date: 29 October 2026.

Sources: [1]

Study design

Other. [1]

Fully reviewed

Review date: 29 October 2026.

Sources: [1]

Measurement

Flow cytometry binding, mast cell degranulation and G protein signaling assays; mutagenesis. [1]

Fully reviewed

Review date: 29 October 2026.

Sources: [1]

Setting and sample

10,000 in silico nanobodies; ten expressed and tested. [1]

Fully reviewed

Review date: 29 October 2026.

Sources: [1]

Measures

Binding affinity and antagonist activity. [1]

Fully reviewed

Review date: 29 October 2026.

Sources: [1]

Comparison

Negative control nanobody (Nb 60). [1]

Fully reviewed

Review date: 29 October 2026.

Sources: [1]

Results

Three binders at 20 to 200 nM that blocked degranulation. [1]

Fully reviewed

Review date: 29 October 2026.

Sources: [1]

Additional value from AI

Not quantified against an experimental screen. [1]

Fully reviewed

Review date: 29 October 2026.

Sources: [1]

Limitations

One receptor; ten candidates; no direct structure of the complex; patent interest of some authors. [1]

Fully reviewed

Review date: 29 October 2026.

Sources: [1]

Denominators

Laboratory. [1]

Fully reviewed

Review date: 29 October 2026.

Sources: [1]

Materials for replication

Ranking code on GitHub; data on request. [1]

Fully reviewed

Review date: 29 October 2026.

Sources: [1]

Money

Kind of value

The kind of monetary value is unclear.

Not reviewedUnresolved

Amount

The monetary value is not established.

Not reviewedUnresolved

Currency and prices

The currency and price basis are unclear.

Not reviewedUnresolved

Period and unit

The period and unit of the monetary estimate are unclear.

Not reviewedUnresolved

Realization

Whether the monetary value was realized is unclear.

Not reviewedUnresolved

Recipients and payers

The recipients and payers are unclear.

Not reviewedUnresolved

Gross or net

Whether the monetary figure includes costs is unclear.

Not reviewedUnresolved

Included costs

The costs included in the estimate are unclear.

Not reviewedUnresolved

Comparison

The financial comparison is not established.

Not reviewedUnresolved

Method

The method used to calculate monetary value is unclear.

Not reviewedUnresolved

Return and payback

The return on investment or payback period is not established.

Not reviewedUnresolved

People and places

Participants

Developer: DeepMind. Operator: Harvard Medical School (Kruse laboratory) and University of California, San Francisco (Susa laboratory).

Awaiting review

Jurisdictions

Benefit: Boston, Massachusetts, and San Francisco, California, United States. Developer: United Kingdom. Operator: United States.

Awaiting review

Ownership and control

Unresolved

Not reviewedUnresolved

Dependencies

Unresolved

Not reviewedUnresolved

Cross-border connections

Unresolved

Not reviewedUnresolved

Geopolitical implications

The geopolitical implications are unclear.

Not reviewedUnresolved

Follow-up

Conditions for replication

The target class must be well represented among solved nanobody complexes. The library must follow a design known to express well.

Awaiting review

Replication attempts

Unresolved

Not reviewedUnresolved

Later findings

Unresolved

Not reviewedUnresolved

Availability

Unresolved

Not reviewedUnresolved

Institutional decision

A relevant institutional decision has not been established.

Not reviewedUnresolved

Grounds

The grounds for an institutional decision are unclear.

Not reviewedUnresolved

Action and result

The result of an institutional decision is not established.

Not reviewedUnresolved

Success criterion

The criterion for a successful institutional decision is unclear.

Not reviewedUnresolved

Evidence

Source numbers

AIBD-0661-source-0001

Awaiting review

Citations

Numbered references below.

Awaiting review

Language

Unresolved

Not reviewedUnresolved

Source relationships

Operator

Awaiting review

Original evidence

Unresolved

Not reviewedUnresolved

Access and versions

Unresolved

Not reviewedUnresolved

Supported findings

Unresolved

Not reviewedUnresolved

Evidence strength

The deployer's account. Sources: the deployer's peer-reviewed study. The cited evidence includes no independent source and no finding by a regulator or court. [1]

Fully reviewed

Review date: 29 October 2026.

Sources: [1]

Missing evidence

Unresolved

Not reviewedUnresolved

Grades

Assessed benefits

Society.

Awaiting review

Depth

Society: 2.

Awaiting review

Reasons

Society: A purely computational screen yielded three nanomolar MRGPRX2 antagonists from ten candidates tested.

Awaiting review

Observed or intended

Unresolved

Not reviewedUnresolved

Rubric

Unresolved

Not reviewedUnresolved

Assessor and date

Unresolved

Not reviewedUnresolved

Alternative assessments

Unresolved

Not reviewedUnresolved

Fill

The deployer's account

Awaiting review

Entry details

Kind

The case describes an evaluation or a study. A prospective laboratory study. [1]

Fully reviewed

Review date: 29 October 2026.

Sources: [1]

Field

Drug discovery.

Awaiting review

Purpose

AlphaFold-Multimer was built to predict the structures of protein complexes. The researchers used it to discover binders, an application by an independent group.

Awaiting review

Dates

Source published: 23 April 2026. Updated: 29 October 2026.

Awaiting review

Stage

The system was tested in a laboratory. Computational screen followed by binding and cell assays. [1]

Fully reviewed

Review date: 29 October 2026.

Sources: [1]

Version

SHA-256: 086ef36ae73b…

Awaiting review

SHA-256 of the public case, its assessments, and its displayed answers and notes, excluding its own identifier and the derived coverage summary.

References

Other identifiers

Unresolved

Not reviewedUnresolved

Category mappings

Unresolved

Not reviewedUnresolved

Citable summary

Unresolved

Not reviewedUnresolved

Revisions

1 revision. Latest: 29 October 2026.

Awaiting review

Sources

  1. Peer-reviewed study Deployer

    Harvey EP, Smith JS, Hurley JD, et al. In silico discovery of nanobody binders to a G-protein coupled receptor using AlphaFold-Multimer. Nat Commun. 2026;17:5641.

Collections: Cross-border cases.

Cite this case

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Version 086ef36ae73b, archived in the edition of 29 October 2026

Benefit marks

Depth

The number and color show the depth of a benefit.

  1. A convenience, or time or money saved.
  2. A measurable improvement in a result or ability.
  3. A lasting change, an ability restored, or a risk removed.
  4. A serious harm averted or a serious condition resolved in time.
  5. A life or livelihood preserved, or a change documented across a population.

Beneficiary

  • Circle: a person
  • Square: an organization
  • Triangle: society

Evidence

  • Solid. A court or regulator found a benefit, or researchers independently studied it.

  • Hatched. Independent reporting.

  • Outline. Claimed by the parties. Only the people or organizations involved, or sources whose independence has not been assessed, support the benefit.

The fill changes with the evidence. The depth color stays the same.

How benefits are assessed