{"id":"AIBD-0661","title":"AlphaFold-Multimer virtual screen finds nanobodies that bind and block the itch receptor MRGPRX2","summary":"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.","date_observed":"2026-04-23","date_basis":"source publication","date_precision":"day","benefit_status":"reported","source_collection":null,"source_entry":null,"account":"Researchers at Harvard Medical School, the University of California, San Francisco and partner institutions used AlphaFold-Multimer to co-fold 10,000 nanobody sequences from a synthetic library design with MRGPRX2, a receptor on mast cells that drives pseudoallergic inflammation and itch. They ranked the pairs by a confidence metric that they had first checked on known nanobody and receptor structures. They expressed and purified ten top-ranked nanobodies. Three (Sim8619, Sim9877 and Sim4784) bound MRGPRX2 with affinities between about 20 and 200 nM and blocked mast cell degranulation caused by Compound 48/80; mutations supported the predicted binding pose. Nature Communications published the study on 23 April 2026. The work is a laboratory proof of concept for one receptor, and some authors are co-inventors on a patent application for the nanobodies.","category":"benefit created","unexpected":false,"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.","system":"AlphaFold-Multimer (AF-M), run through a modified ColabFold script","model_version":null,"developer":"DeepMind","deployer":"Harvard Medical School (Kruse laboratory) and University of California, San Francisco (Susa laboratory)","location":"Boston, Massachusetts, and San Francisco, California, United States","domain":"Drug discovery","segment":null,"benefit_type":"Improved Knowledge Discovery","taxonomy_note":null,"registry_ids":{},"ratings":[{"group":"societal","depth":2,"reason":"A purely computational screen yielded three nanomolar MRGPRX2 antagonists from ten candidates tested."}],"ai_role":{"status":"unassessed","statement":"The authors tested only AlphaFold-Multimer picks; they had no arm with randomly chosen or experimentally screened nanobodies."},"evidence":[{"kind":"peer-reviewed study","citation":"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.","title":"In silico discovery of nanobody binders to a G-protein coupled receptor using AlphaFold-Multimer","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13315262/","date":"2026-04-23","written_by":"deployer","quote":"Moreover, in a prospective screen of an in silico nanobody library of 10,000 nanobodies, we identified binders ranging in affinity from 20 to 200 nanomolar to MRGPRX2"}],"replication":{"produced_by":["The team checked that the confidence metric separated known binders from non-binders.","Ten top-ranked nanobodies were made and tested."],"must_hold":["The target class must be well represented among solved nanobody complexes.","The library must follow a design known to express well."],"echoes":[]},"paired_incident":null,"headline":"A computer screen finds antibody fragments for an itch receptor","metric":"bound MRGPRX2 with affinities between about 20 and 200 nM","comparator":null,"later":null,"value":null,"developer_country":"United Kingdom","deployer_country":"United States","unrated_because":null,"brief_notes":null,"brief":null,"revisions":[{"date":"2026-10-29","change":"Added the case.","source":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13315262/","editor":"AIBD"}],"confidence":"claimed","shade":"low","claim_status":"The deployer's account","claim_basis":"Sources: the deployer's peer-reviewed study. The cited evidence includes no independent source and no finding by a regulator or court.","case_jurisdictions":["United States"],"profile":{"case_id":"AIBD-0661","catalog_version":"1.0.0","source_fingerprint":"e2cfdf916ca63a5c97494f48ad675c1e40d3a4ed85836aee6165adaa1c516e92","collection_refs":[{"collection_id":"aibd","version":"2026-10-29"},{"collection_id":"viator","version":"2026-10-25"}],"source_ids":["AIBD-0661-source-0001"],"families":{"strategic assessments":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"Editorial assignment.","review_state":"not_assessed","coverage":"partial","record_ids":[]},"evaluations":{"state":"value_present","value":{"kind":"identifiers","identifiers":["AIBD-0661-evaluation-1"],"role":"Evaluations of the benefit"},"provenance":{"kind":"source_review","basis":"Editorial assignment.","record_fields":[],"source_refs":["AIBD-0661-source-0001"],"reviewed_on":"2026-10-29"},"review_state":"reviewed","coverage":"partial","record_ids":["AIBD-0661-evaluation-1"]},"monetary observations":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"Editorial assignment.","review_state":"not_assessed","coverage":"partial","record_ids":[]},"institutional decisions":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"Editorial assignment.","review_state":"not_assessed","coverage":"partial","record_ids":[]}},"fields":{"actors[]":{"state":"value_present","value":{"kind":"record_fields","fields":{"developer":"DeepMind","deployer":"Harvard Medical School (Kruse laboratory) and University of California, San Francisco (Susa laboratory)"}},"provenance":{"kind":"legacy_record","basis":"Editorial assignment.","record_fields":["developer","deployer"],"source_refs":[]},"review_state":"record_mapped","coverage":"partial"},"actors[].ownership_control":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"ai_contribution":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"ai_relationship":{"state":"value_present","value":{"kind":"record_fields","fields":{"category":"benefit created","ai_role":{"status":"unassessed","statement":"The authors tested only AlphaFold-Multimer picks; they had no arm with randomly chosen or experimentally screened nanobodies."}}},"provenance":{"kind":"legacy_record","basis":"Editorial assignment.","record_fields":["ai_role","category"],"source_refs":[]},"review_state":"record_mapped","coverage":"partial"},"assessments[].alternatives":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"assessments[].assessor_date":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"assessments[].depth":{"state":"value_present","value":{"kind":"record_fields","fields":{"ratings":[{"group":"societal","depth":2,"reason":"A purely computational screen yielded three nanomolar MRGPRX2 antagonists from ten candidates tested."}]}},"provenance":{"kind":"legacy_record","basis":"Editorial assignment.","record_fields":["ratings"],"source_refs":[]},"review_state":"record_mapped","coverage":"partial"},"assessments[].display_confidence":{"state":"value_present","value":{"kind":"structured","data":{"confidence":"low","evidence_word":"claimed","claim_status":"The deployer's account","basis":"Sources: the deployer's peer-reviewed study. The cited evidence includes no independent source and no finding by a regulator or court.","interpretation":"Existing display rule preserved; the richer outcome-specific confidence question still needs review."}},"provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"review_state":"record_mapped","coverage":"partial"},"assessments[].rationale":{"state":"value_present","value":{"kind":"record_fields","fields":{"ratings":[{"group":"societal","depth":2,"reason":"A purely computational screen yielded three nanomolar MRGPRX2 antagonists from ten candidates tested."}]}},"provenance":{"kind":"legacy_record","basis":"Editorial assignment.","record_fields":["ratings"],"source_refs":[]},"review_state":"record_mapped","coverage":"partial"},"assessments[].rubric_version":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"assessments[].status_basis":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"assessments[].target":{"state":"value_present","value":{"kind":"record_fields","fields":{"ratings":[{"group":"societal","depth":2,"reason":"A purely computational screen yielded three nanomolar MRGPRX2 antagonists from ten candidates tested."}]}},"provenance":{"kind":"legacy_record","basis":"Editorial assignment.","record_fields":["ratings"],"source_refs":[]},"review_state":"record_mapped","coverage":"partial"},"availability":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"brief":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"case_kind":{"state":"value_present","value":{"kind":"structured","data":{"classification":"evaluation or study","answer":"The case describes an evaluation or a study. A prospective laboratory study.","scope":"The period and activity described in the case."}},"provenance":{"kind":"source_review","basis":"Editorial assignment.","record_fields":["account","evidence"],"source_refs":["AIBD-0661-source-0001"],"reviewed_on":"2026-10-29"},"review_state":"reviewed","coverage":"complete","display":{"answer":"The case describes an evaluation or a study. A prospective laboratory study.","inferred":false}},"case_links[]":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Compared with the incidents in the AI Incident Database snapshot of 26 October 2026.","record_fields":["paired_incident"],"source_refs":[]},"reason":"No incident in the AI Incident Database snapshot of 26 October 2026 concerns the same kind of system harming the same kind of stakeholder.","review_state":"reviewed","coverage":"partial"},"claims[].evidence_links":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"claims[].evidence_strength":{"state":"value_present","value":{"kind":"structured","data":{"answer":"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.","evidence_word":"claimed","claim_status":"The deployer's account"}},"provenance":{"kind":"source_review","basis":"Editorial assignment.","record_fields":["evidence"],"source_refs":["AIBD-0661-source-0001"],"reviewed_on":"2026-10-29"},"review_state":"reviewed","coverage":"complete","display":{"answer":"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.","inferred":false}},"claims[].missingness":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"claims[].proposition":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"cross_border_flows[]":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"decisions[].action_outcome":{"state":"unresolved","review_state":"not_assessed","coverage":"partial","family":"institutional decisions"},"decisions[].grounds":{"state":"unresolved","review_state":"not_assessed","coverage":"partial","family":"institutional decisions"},"decisions[].institution_task":{"state":"unresolved","review_state":"not_assessed","coverage":"partial","family":"institutional decisions"},"decisions[].success_criterion":{"state":"unresolved","review_state":"not_assessed","coverage":"partial","family":"institutional decisions"},"deployment_stage":{"state":"value_present","value":{"kind":"structured","data":{"classification":"laboratory test","answer":"The system was tested in a laboratory. Computational screen followed by binding and cell assays.","scope":"The period and activity described in the case."}},"provenance":{"kind":"source_review","basis":"Editorial assignment.","record_fields":["account","evidence"],"source_refs":["AIBD-0661-source-0001"],"reviewed_on":"2026-10-29"},"review_state":"reviewed","coverage":"complete","display":{"answer":"The system was tested in a laboratory. Computational screen followed by binding and cell assays.","inferred":false}},"economics[].amount":{"state":"unresolved","review_state":"not_assessed","coverage":"partial","family":"monetary observations"},"economics[].costs[]":{"state":"unresolved","review_state":"not_assessed","coverage":"partial","family":"monetary observations"},"economics[].counterfactual":{"state":"unresolved","review_state":"not_assessed","coverage":"partial","family":"monetary observations"},"economics[].currency_price_basis":{"state":"unresolved","review_state":"not_assessed","coverage":"partial","family":"monetary observations"},"economics[].gross_net":{"state":"unresolved","review_state":"not_assessed","coverage":"partial","family":"monetary observations"},"economics[].measure_type":{"state":"unresolved","review_state":"not_assessed","coverage":"partial","family":"monetary observations"},"economics[].period_unit":{"state":"unresolved","review_state":"not_assessed","coverage":"partial","family":"monetary observations"},"economics[].realization":{"state":"unresolved","review_state":"not_assessed","coverage":"partial","family":"monetary observations"},"economics[].recipient_payer":{"state":"unresolved","review_state":"not_assessed","coverage":"partial","family":"monetary observations"},"economics[].return_payback":{"state":"unresolved","review_state":"not_assessed","coverage":"partial","family":"monetary observations"},"economics[].valuation_method":{"state":"unresolved","review_state":"not_assessed","coverage":"partial","family":"monetary observations"},"evaluations[].ai_uplift":{"state":"value_present","value":{"kind":"text","text":"Not quantified against an experimental screen."},"provenance":{"kind":"source_review","basis":"Editorial assignment.","record_fields":["evidence"],"source_refs":["AIBD-0661-source-0001"],"reviewed_on":"2026-10-29"},"review_state":"reviewed","coverage":"complete","display":{"answer":"Not quantified against an experimental screen.","inferred":false}},"evaluations[].comparator":{"state":"value_present","value":{"kind":"text","text":"Negative control nanobody (Nb 60)."},"provenance":{"kind":"source_review","basis":"Editorial assignment.","record_fields":["evidence"],"source_refs":["AIBD-0661-source-0001"],"reviewed_on":"2026-10-29"},"review_state":"reviewed","coverage":"complete","display":{"answer":"Negative control nanobody (Nb 60).","inferred":false}},"evaluations[].design":{"state":"value_present","value":{"kind":"text","text":"Other."},"provenance":{"kind":"source_review","basis":"Editorial assignment.","record_fields":["evidence"],"source_refs":["AIBD-0661-source-0001"],"reviewed_on":"2026-10-29"},"review_state":"reviewed","coverage":"complete","display":{"answer":"Other.","inferred":false}},"evaluations[].effect":{"state":"value_present","value":{"kind":"text","text":"Three binders at 20 to 200 nM that blocked degranulation."},"provenance":{"kind":"source_review","basis":"Editorial assignment.","record_fields":["evidence"],"source_refs":["AIBD-0661-source-0001"],"reviewed_on":"2026-10-29"},"review_state":"reviewed","coverage":"complete","display":{"answer":"Three binders at 20 to 200 nM that blocked degranulation.","inferred":false}},"evaluations[].exposure":{"state":"value_present","value":{"kind":"text","text":"Laboratory."},"provenance":{"kind":"source_review","basis":"Editorial assignment.","record_fields":["evidence"],"source_refs":["AIBD-0661-source-0001"],"reviewed_on":"2026-10-29"},"review_state":"reviewed","coverage":"complete","display":{"answer":"Laboratory.","inferred":false}},"evaluations[].id":{"state":"value_present","value":{"kind":"identifiers","identifiers":["AIBD-0661-evaluation-1"],"role":"Evaluations of the benefit"},"provenance":{"kind":"source_review","basis":"Editorial assignment.","record_fields":["evidence"],"source_refs":["AIBD-0661-source-0001"],"reviewed_on":"2026-10-29"},"review_state":"reviewed","coverage":"complete","display":{"answer":"Other.","inferred":false}},"evaluations[].measurement_method":{"state":"value_present","value":{"kind":"text","text":"Flow cytometry binding, mast cell degranulation and G protein signaling assays; mutagenesis."},"provenance":{"kind":"source_review","basis":"Editorial assignment.","record_fields":["evidence"],"source_refs":["AIBD-0661-source-0001"],"reviewed_on":"2026-10-29"},"review_state":"reviewed","coverage":"complete","display":{"answer":"Flow cytometry binding, mast cell degranulation and G protein signaling assays; mutagenesis.","inferred":false}},"evaluations[].metric":{"state":"value_present","value":{"kind":"text","text":"Binding affinity and antagonist activity."},"provenance":{"kind":"source_review","basis":"Editorial assignment.","record_fields":["evidence"],"source_refs":["AIBD-0661-source-0001"],"reviewed_on":"2026-10-29"},"review_state":"reviewed","coverage":"complete","display":{"answer":"Binding affinity and antagonist activity.","inferred":false}},"evaluations[].reproduction_materials":{"state":"value_present","value":{"kind":"text","text":"Ranking code on GitHub; data on request."},"provenance":{"kind":"source_review","basis":"Editorial assignment.","record_fields":["evidence"],"source_refs":["AIBD-0661-source-0001"],"reviewed_on":"2026-10-29"},"review_state":"reviewed","coverage":"complete","display":{"answer":"Ranking code on GitHub; data on request.","inferred":false}},"evaluations[].setting_sample":{"state":"value_present","value":{"kind":"text","text":"10,000 in silico nanobodies; ten expressed and tested."},"provenance":{"kind":"source_review","basis":"Editorial assignment.","record_fields":["evidence"],"source_refs":["AIBD-0661-source-0001"],"reviewed_on":"2026-10-29"},"review_state":"reviewed","coverage":"complete","display":{"answer":"10,000 in silico nanobodies; ten expressed and tested.","inferred":false}},"evaluations[].uncertainty_limitations":{"state":"value_present","value":{"kind":"text","text":"One receptor; ten candidates; no direct structure of the complex; patent interest of some authors."},"provenance":{"kind":"source_review","basis":"Editorial assignment.","record_fields":["evidence"],"source_refs":["AIBD-0661-source-0001"],"reviewed_on":"2026-10-29"},"review_state":"reviewed","coverage":"complete","display":{"answer":"One receptor; ten candidates; no direct structure of the complex; patent interest of some authors.","inferred":false}},"external_references[]":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"follow_up[]":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"human_oversight":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"id":{"state":"value_present","value":{"kind":"record_fields","fields":{"id":"AIBD-0661"}},"provenance":{"kind":"legacy_record","basis":"Editorial assignment.","record_fields":["id"],"source_refs":[]},"review_state":"record_mapped","coverage":"partial"},"infrastructure_dependencies[]":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"outcomes[].beneficiaries":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"outcomes[].beneficiary_count":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"outcomes[].benefit_type":{"state":"value_present","value":{"kind":"record_fields","fields":{"benefit_type":"Improved Knowledge Discovery"}},"provenance":{"kind":"legacy_record","basis":"Editorial assignment.","record_fields":["benefit_type"],"source_refs":[]},"review_state":"record_mapped","coverage":"partial"},"outcomes[].claim":{"state":"value_present","value":{"kind":"record_fields","fields":{"account":"Researchers at Harvard Medical School, the University of California, San Francisco and partner institutions used AlphaFold-Multimer to co-fold 10,000 nanobody sequences from a synthetic library design with MRGPRX2, a receptor on mast cells that drives pseudoallergic inflammation and itch. They ranked the pairs by a confidence metric that they had first checked on known nanobody and receptor structures. They expressed and purified ten top-ranked nanobodies. Three (Sim8619, Sim9877 and Sim4784) bound MRGPRX2 with affinities between about 20 and 200 nM and blocked mast cell degranulation caused by Compound 48/80; mutations supported the predicted binding pose. Nature Communications published the study on 23 April 2026. The work is a laboratory proof of concept for one receptor, and some authors are co-inventors on a patent application for the nanobodies.","benefit_type":"Improved Knowledge Discovery"}},"provenance":{"kind":"legacy_record","basis":"Editorial assignment.","record_fields":["account","benefit_type"],"source_refs":[]},"review_state":"record_mapped","coverage":"partial"},"outcomes[].distribution":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"outcomes[].duration":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"outcomes[].id":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"outcomes[].stakeholder_group":{"state":"value_present","value":{"kind":"record_fields","fields":{"ratings":[{"group":"societal","depth":2,"reason":"A purely computational screen yielded three nanomolar MRGPRX2 antagonists from ten candidates tested."}]}},"provenance":{"kind":"legacy_record","basis":"Editorial assignment.","record_fields":["ratings"],"source_refs":[]},"review_state":"record_mapped","coverage":"partial"},"outcomes[].status":{"state":"value_present","value":{"kind":"record_fields","fields":{"benefit_status":"reported"}},"provenance":{"kind":"legacy_record","basis":"Editorial assignment.","record_fields":["benefit_status"],"source_refs":[]},"review_state":"record_mapped","coverage":"partial"},"outcomes[].tradeoffs":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"outcomes[].unexpected":{"state":"value_present","value":{"kind":"record_fields","fields":{"unexpected":false,"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."}},"provenance":{"kind":"legacy_record","basis":"Editorial assignment.","record_fields":["unexpected","purpose"],"source_refs":[]},"review_state":"record_mapped","coverage":"partial"},"places[]":{"state":"value_present","value":{"kind":"record_fields","fields":{"location":"Boston, Massachusetts, and San Francisco, California, United States","developer_country":"United Kingdom","deployer_country":"United States"}},"provenance":{"kind":"legacy_record","basis":"Editorial assignment.","record_fields":["location","developer_country","deployer_country"],"source_refs":[]},"review_state":"record_mapped","coverage":"partial"},"purpose":{"state":"value_present","value":{"kind":"record_fields","fields":{"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."}},"provenance":{"kind":"legacy_record","basis":"Editorial assignment.","record_fields":["purpose"],"source_refs":[]},"review_state":"record_mapped","coverage":"partial"},"record_dates":{"state":"value_present","value":{"kind":"record_fields","fields":{"date_observed":"2026-04-23","date_basis":"source publication","date_precision":"day","revisions":[{"date":"2026-10-29","change":"Added the case.","source":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13315262/","editor":"AIBD"}]}},"provenance":{"kind":"legacy_record","basis":"Editorial assignment.","record_fields":["date_observed","date_basis","date_precision","revisions"],"source_refs":[]},"review_state":"record_mapped","coverage":"partial"},"replication.attempts[]":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"replication.conditions":{"state":"value_present","value":{"kind":"record_fields","fields":{"replication":{"produced_by":["The team checked that the confidence metric separated known binders from non-binders.","Ten top-ranked nanobodies were made and tested."],"must_hold":["The target class must be well represented among solved nanobody complexes.","The library must follow a design known to express well."],"echoes":[]}}},"provenance":{"kind":"legacy_record","basis":"Editorial assignment.","record_fields":["replication"],"source_refs":[]},"review_state":"record_mapped","coverage":"partial"},"revision_history[]":{"state":"value_present","value":{"kind":"record_fields","fields":{"revisions":[{"date":"2026-10-29","change":"Added the case.","source":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13315262/","editor":"AIBD"}]}},"provenance":{"kind":"legacy_record","basis":"Editorial assignment.","record_fields":["revisions"],"source_refs":[]},"review_state":"record_mapped","coverage":"partial"},"sector":{"state":"value_present","value":{"kind":"record_fields","fields":{"domain":"Drug discovery"}},"provenance":{"kind":"legacy_record","basis":"Editorial assignment.","record_fields":["domain"],"source_refs":[]},"review_state":"record_mapped","coverage":"partial"},"sources[].access_version":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"sources[].citation_locator":{"state":"value_present","value":{"kind":"record_fields","fields":{"evidence":[{"kind":"peer-reviewed study","citation":"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.","title":"In silico discovery of nanobody binders to a G-protein coupled receptor using AlphaFold-Multimer","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13315262/","date":"2026-04-23","written_by":"deployer","quote":"Moreover, in a prospective screen of an in silico nanobody library of 10,000 nanobodies, we identified binders ranging in affinity from 20 to 200 nanomolar to MRGPRX2"}]}},"provenance":{"kind":"legacy_record","basis":"Editorial assignment.","record_fields":["evidence"],"source_refs":[]},"review_state":"record_mapped","coverage":"partial"},"sources[].id":{"state":"value_present","value":{"kind":"identifiers","identifiers":["AIBD-0661-source-0001"],"role":"Existing evidence items, in their original order"},"provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"review_state":"record_mapped","coverage":"complete"},"sources[].language":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"sources[].relationship":{"state":"value_present","value":{"kind":"record_fields","fields":{"evidence":[{"kind":"peer-reviewed study","citation":"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.","title":"In silico discovery of nanobody binders to a G-protein coupled receptor using AlphaFold-Multimer","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13315262/","date":"2026-04-23","written_by":"deployer","quote":"Moreover, in a prospective screen of an in silico nanobody library of 10,000 nanobodies, we identified binders ranging in affinity from 20 to 200 nanomolar to MRGPRX2"}]}},"provenance":{"kind":"legacy_record","basis":"Editorial assignment.","record_fields":["evidence"],"source_refs":[]},"review_state":"record_mapped","coverage":"partial"},"sources[].upstream_sources":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"strategic_assessments[]":{"state":"unresolved","review_state":"not_assessed","coverage":"partial","family":"strategic assessments"},"summary":{"state":"value_present","value":{"kind":"record_fields","fields":{"summary":"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.","account":"Researchers at Harvard Medical School, the University of California, San Francisco and partner institutions used AlphaFold-Multimer to co-fold 10,000 nanobody sequences from a synthetic library design with MRGPRX2, a receptor on mast cells that drives pseudoallergic inflammation and itch. They ranked the pairs by a confidence metric that they had first checked on known nanobody and receptor structures. They expressed and purified ten top-ranked nanobodies. Three (Sim8619, Sim9877 and Sim4784) bound MRGPRX2 with affinities between about 20 and 200 nM and blocked mast cell degranulation caused by Compound 48/80; mutations supported the predicted binding pose. Nature Communications published the study on 23 April 2026. The work is a laboratory proof of concept for one receptor, and some authors are co-inventors on a patent application for the nanobodies."}},"provenance":{"kind":"legacy_record","basis":"Editorial assignment.","record_fields":["summary","account"],"source_refs":[]},"review_state":"record_mapped","coverage":"partial"},"systems[].autonomy_permissions":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"systems[].component_role":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"systems[].deployment_configuration":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"systems[].inputs_outputs":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"systems[].model_name":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"systems[].model_version":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"systems[].product_name":{"state":"value_present","value":{"kind":"record_fields","fields":{"system":"AlphaFold-Multimer (AF-M), run through a modified ColabFold script"}},"provenance":{"kind":"legacy_record","basis":"Editorial assignment.","record_fields":["system"],"source_refs":[]},"review_state":"record_mapped","coverage":"partial"},"systems[].provider":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"taxonomy_crosswalks[]":{"state":"unresolved","provenance":{"kind":"curatorial","basis":"Editorial assignment.","record_fields":[],"source_refs":[]},"reason":"This is an explicit unresolved assignment: the sources on record do not settle this question.","review_state":"not_assessed","coverage":"partial"},"title":{"state":"value_present","value":{"kind":"record_fields","fields":{"title":"AlphaFold-Multimer virtual screen finds nanobodies that bind and block the itch receptor MRGPRX2","headline":"A computer screen finds antibody fragments for an itch receptor"}},"provenance":{"kind":"legacy_record","basis":"Editorial assignment.","record_fields":["title","headline"],"source_refs":[]},"review_state":"record_mapped","coverage":"partial"},"version":{"state":"value_present","value":{"kind":"identifiers","identifiers":["086ef36ae73b72ac087a8597e21d1f1a7843fab4b1850985d297323632548391"],"role":"SHA-256 of the complete public case and its assessments"},"provenance":{"kind":"curatorial","basis":"SHA-256 of the public case, its assessments, and its displayed answers and notes, excluding its own identifier and the derived coverage summary.","record_fields":[],"source_refs":[]},"review_state":"record_mapped","coverage":"complete"},"workflow":{"state":"value_present","value":{"kind":"record_fields","fields":{"account":"Researchers at Harvard Medical School, the University of California, San Francisco and partner institutions used AlphaFold-Multimer to co-fold 10,000 nanobody sequences from a synthetic library design with MRGPRX2, a receptor on mast cells that drives pseudoallergic inflammation and itch. They ranked the pairs by a confidence metric that they had first checked on known nanobody and receptor structures. They expressed and purified ten top-ranked nanobodies. Three (Sim8619, Sim9877 and Sim4784) bound MRGPRX2 with affinities between about 20 and 200 nM and blocked mast cell degranulation caused by Compound 48/80; mutations supported the predicted binding pose. Nature Communications published the study on 23 April 2026. The work is a laboratory proof of concept for one receptor, and some authors are co-inventors on a patent application for the nanobodies.","replication":{"produced_by":["The team checked that the confidence metric separated known binders from non-binders.","Ten top-ranked nanobodies were made and tested."],"must_hold":["The target class must be well represented among solved nanobody complexes.","The library must follow a design known to express well."],"echoes":[]}}},"provenance":{"kind":"legacy_record","basis":"Editorial assignment.","record_fields":["account","replication"],"source_refs":[]},"review_state":"record_mapped","coverage":"partial"}},"summary":{"total":91,"addressed":91,"known":40,"reviewed":15,"reviewed_complete":14,"reviewed_partial":1,"record_mapped":26,"review_not_assessed":50,"not_assessed":0,"complete":false,"by_state":{"value_present":40,"not_reported":0,"unresolved":51,"not_assessed":0,"not_applicable":0,"withheld":0,"source_unavailable":0}}},"presentation_version":"d46768be1bec0f7e2d456bf081de976b2e9b33d879a1680a24d4743f20fc418b"}