Evidence claim
Summary of the de novo binder design evidence
Summary of Design a new binder to a chosen target
Four studies, pinned here as seven artifacts, carry measured outcomes for de novo binder design, and none of them answers which workflow to use, because no paper runs two design methods and a conventional comparator on the same targets with one assay and one hit definition. The literature pass behind this evidence found nine candidate sources with measured outcomes; the five that were not retrieved are recorded as gaps rather than as evidence of what they would show. What the measured evidence shows is that the target matters more than the method. AlphaProteo's yeast-display success rate across eight targets runs from 0% over 54 designs on TNF-alpha to 88% over 94 designs on BHRF1, at a binding-signal threshold of 0.2 (1.3 on IL-17A). BindCraft reports an average experimental success rate of 46.3% over twelve targets with a range of 10% to 100%, built from per-target counts as small as 2 binders from 7 designs on Bet v1 and as large as 6 from 6 on the SpCas9 REC1 domain. The same family of methods applied to antibody variable domains is two orders of magnitude worse: fine-tuned RFdiffusion gives 2% over 96 designs on TcdB, 0% over 96 on IL-7 receptor alpha, and 0.01% to 0.2% over 9,000 designs per target by yeast display. On influenza H1 stem the same design campaign gives 1% over 96 designs by SPR and 0.2% over 9,000 by display, so the screening method moves the rate as much as the target does. Nearly all of this is author-reported by the group that built the method, which also chose the targets, ran the assay and chose which designs to test. The exception is the Adaptyv EGFR competition, where a third-party laboratory expressed and measured designs from many entrants on one target and one assay: 2.5% of 201 round-1 designs bound (printed elsewhere in the same paper as 3%), and 53 of 400 round-2 designs bound, printed as 13%. That source cannot be turned into a per-method rate: design methods are the entrants' own declarations, the organisers hand-picked 101 of 201 round-1 and 300 of 400 round-2 designs for diversity, and the three binding thresholds behind the figure counts are never defined. Affinities reached are better than the hit rates suggest. AlphaProteo's best measured binder was 0.082 nM on IL-7 receptor alpha by HTRF; BindCraft's best ranged from 5 nM on CbAgo to 5.7 micromolar on CrSAS-6; the best de novo design in the Adaptyv competition reached 82 nM and the winning optimised cetuximab fragment 1.21 nM, against 9.94 nM for the cetuximab positive control measured on the same instrument. Three things stop these numbers from ranking methods. The hit definitions are different endpoints, not different thresholds on one endpoint. The denominators are small and chosen, and the designs tested are the top picks of each method's own filter, so design and selection are coupled: changing only AlphaProteo's filter moved its PD-L1 rate from 9.6% over 94 designs to 16.1% over 31, and the Bennett authors attribute their low antibody rates partly to a filter they describe as weak. And the spread within one method across targets is wider than any plausible difference between methods. No conventional comparator is run anywhere in this evidence, so there is no measurement of what a designed binder is being compared against.
A descriptive account of what the reviewed evidence shows about de novo binder design: the per-target spread, the antibody-versus-miniprotein gap, the author-reported nature of nearly all of it, and the absence of any controlled cross-method comparison. It makes no recommendation.
Evidence
Source checking verifies the cited claim or transcription. It does not establish independent reproduction.
Evidence table
Inspect claims, sources and review details
Trace each statement to its source and review. A context-only reference supports the record generally; it does not verify an individual field. Source checking does not reproduce an experiment.
One row per statement and cited source. Multiple citations are not independent evaluations. Shared locators are labelled explicitly.
63 evidence rows matching the loaded filters
| Property and statement | Original source and location | Review and provenance |
|---|---|---|
| Claimed field summary Context-only references | Crowdsourced Protein Design: Lessons From the Adaptyv EGFR Binder Competition (Cotet et al., bioRxiv 2025) AlphaProteo Table 1, Table S2 and Sections S1.2.1, S2 and S4.1; BindCraft Introduction and Results prose; Bennett Supplementary Methods Table 6; Adaptyv Sections 2.3, 2.4, 3.1, 3.2, 4.1, 4.2 and 4.3 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: bioRxiv preprint version 1 | not individually reviewed No individual claim review recorded Source has a recorded evidence concern. Consult its source page before using the claim. Audit detailsField: Source artifact SHA-256: Hash scope: SHA-256 of one retrieval of a mutable web page. The hash describes that retrieval, not a stable artifact. |
| Claimed field summary Context-only references | Adaptyv EGFR design competition round 2 results repository AlphaProteo Table 1, Table S2 and Sections S1.2.1, S2 and S4.1; BindCraft Introduction and Results prose; Bennett Supplementary Methods Table 6; Adaptyv Sections 2.3, 2.4, 3.1, 3.2, 4.1, 4.2 and 4.3 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: commit fc91b91ddc367830b755b215dbc69669675ad6a0 | not individually reviewed No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: Hash scope not separately documented; inspect source record Archive member: results/result_summary.csv at commit fc91b91ddc367830b755b215dbc69669675ad6a0 |
| Claimed field summary Context-only references | De novo design of high-affinity protein binders with AlphaProteo (Zambaldi et al., arXiv 2024) AlphaProteo Table 1, Table S2 and Sections S1.2.1, S2 and S4.1; BindCraft Introduction and Results prose; Bennett Supplementary Methods Table 6; Adaptyv Sections 2.3, 2.4, 3.1, 3.2, 4.1, 4.2 and 4.3 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: arXiv version 1, posted 2024-09-12; full-text PDF (49 pages) | not individually reviewed No individual claim review recorded Source has a recorded evidence concern. Consult its source page before using the claim. Audit detailsField: Source artifact SHA-256: Hash scope: SHA-256 of one retrieval of the arXiv v1 PDF on 2026-10-22. |
| Claimed field summary Context-only references | Atomically accurate de novo design of antibodies with RFdiffusion (Bennett et al., Nature 2025) AlphaProteo Table 1, Table S2 and Sections S1.2.1, S2 and S4.1; BindCraft Introduction and Results prose; Bennett Supplementary Methods Table 6; Adaptyv Sections 2.3, 2.4, 3.1, 3.2, 4.1, 4.2 and 4.3 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: Nature, version of record; Europe PMC JATS full text for PMC12727541 | not individually reviewed No individual claim review recorded Source has a recorded evidence concern. Consult its source page before using the claim. Audit detailsField: Source artifact SHA-256: Hash scope: Hash scope not separately documented; inspect source record |
| Claimed field summary Context-only references | Bennett 2025 Supplementary Information, including Supplementary Methods Tables 5 and 6 AlphaProteo Table 1, Table S2 and Sections S1.2.1, S2 and S4.1; BindCraft Introduction and Results prose; Bennett Supplementary Methods Table 6; Adaptyv Sections 2.3, 2.4, 3.1, 3.2, 4.1, 4.2 and 4.3 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: Supplementary Information PDF 41586_2025_9721_MOESM1_ESM.pdf, 129 pages, InDesign 17.4, ModDate 2026-09-15 | not individually reviewed No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: SHA-256 of the Supplementary Information PDF as extracted from one retrieval of the supplementary archive on 2026-10-22. The archive itself was truncated (103,690,987 bytes, SHA-256 6b1bd61ba4d69d5393f56e0e0d12bb4349b45ce12496a1d3e6a5a8467c39203a) and is not the pinned artifact. Archive member: 41586_2025_9721_MOESM1_ESM.pdf, extracted from the Europe PMC supplementaryFiles archive for PMC12727541 |
| Claimed field summary Context-only references | One-shot design of functional protein binders with BindCraft (Pacesa et al., Nature 2025) AlphaProteo Table 1, Table S2 and Sections S1.2.1, S2 and S4.1; BindCraft Introduction and Results prose; Bennett Supplementary Methods Table 6; Adaptyv Sections 2.3, 2.4, 3.1, 3.2, 4.1, 4.2 and 4.3 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: Nature, version of record; Europe PMC JATS full text for PMC12507698 | not individually reviewed No individual claim review recorded Source has a recorded evidence concern. Consult its source page before using the claim. Audit detailsField: Source artifact SHA-256: Hash scope: Hash scope not separately documented; inspect source record |
| Claimed field summary Context-only references | BindCraft Supplementary Information and Supplementary Data 1 (Pacesa et al., Nature 2025) AlphaProteo Table 1, Table S2 and Sections S1.2.1, S2 and S4.1; BindCraft Introduction and Results prose; Bennett Supplementary Methods Table 6; Adaptyv Sections 2.3, 2.4, 3.1, 3.2, 4.1, 4.2 and 4.3 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: Supplementary files archive for PMC12507698, holding 41586_2025_9429_MOESM1_ESM.pdf (Supplementary Text, Figs. 1-6, Table 1 and References) and 41586_2025_9429_MOESM4_ESM.csv (Supplementary Data 1) | not individually reviewed No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: SHA-256 of one retrieval of the whole supplementary archive. Member hashes: Supplementary Information PDF and Supplementary Data 1 CSV were read from this archive without re-download. |
Pinned records315 values
| Crowdsourced Protein Design: Lessons From the Adaptyv EGFR Binder Competition (Cotet et al., bioRxiv 2025) AlphaProteo Table 1, Table S2 and Sections S1.2.1, S2 and S4.1; BindCraft Introduction and Results prose; Bennett Supplementary Methods Table 6; Adaptyv Sections 2.3, 2.4, 3.1, 3.2, 4.1, 4.2 and 4.3 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: bioRxiv preprint version 1 | not individually reviewed No individual claim review recorded Source has a recorded evidence concern. Consult its source page before using the claim. Audit detailsField: Source artifact SHA-256: Hash scope: SHA-256 of one retrieval of a mutable web page. The hash describes that retrieval, not a stable artifact. |
Pinned records315 values
| Adaptyv EGFR design competition round 2 results repository AlphaProteo Table 1, Table S2 and Sections S1.2.1, S2 and S4.1; BindCraft Introduction and Results prose; Bennett Supplementary Methods Table 6; Adaptyv Sections 2.3, 2.4, 3.1, 3.2, 4.1, 4.2 and 4.3 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: commit fc91b91ddc367830b755b215dbc69669675ad6a0 | not individually reviewed No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: Hash scope not separately documented; inspect source record Archive member: results/result_summary.csv at commit fc91b91ddc367830b755b215dbc69669675ad6a0 |
Pinned records315 values
| De novo design of high-affinity protein binders with AlphaProteo (Zambaldi et al., arXiv 2024) AlphaProteo Table 1, Table S2 and Sections S1.2.1, S2 and S4.1; BindCraft Introduction and Results prose; Bennett Supplementary Methods Table 6; Adaptyv Sections 2.3, 2.4, 3.1, 3.2, 4.1, 4.2 and 4.3 Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: arXiv version 1, posted 2024-09-12; full-text PDF (49 pages) | not individually reviewed No individual claim review recorded Source has a recorded evidence concern. Consult its source page before using the claim. Audit detailsField: Source artifact SHA-256: Hash scope: SHA-256 of one retrieval of the arXiv v1 PDF on 2026-10-22. |
Sources and history
Release 2026-10-22-1b7cf027e4f6 · Record review: source checked
7 source records and release history
- De novo design of high-affinity protein binders with AlphaProteo (Zambaldi et al., arXiv 2024) · Original source · arXiv version 1, posted 2024-09-12; full-text PDF (49 pages)
- One-shot design of functional protein binders with BindCraft (Pacesa et al., Nature 2025) · Original source · Nature, version of record; Europe PMC JATS full text for PMC12507698
- BindCraft Supplementary Information and Supplementary Data 1 (Pacesa et al., Nature 2025) · Original source · Supplementary files archive for PMC12507698, holding 41586_2025_9429_MOESM1_ESM.pdf (Supplementary Text, Figs. 1-6, Table 1 and References) and 41586_2025_9429_MOESM4_ESM.csv (Supplementary Data 1)
- Atomically accurate de novo design of antibodies with RFdiffusion (Bennett et al., Nature 2025) · Original source · Nature, version of record; Europe PMC JATS full text for PMC12727541
- Bennett 2025 Supplementary Information, including Supplementary Methods Tables 5 and 6 · Original source · Supplementary Information PDF 41586_2025_9721_MOESM1_ESM.pdf, 129 pages, InDesign 17.4, ModDate 2026-09-15
- Crowdsourced Protein Design: Lessons From the Adaptyv EGFR Binder Competition (Cotet et al., bioRxiv 2025) · Original source · bioRxiv preprint version 1
- Adaptyv EGFR design competition round 2 results repository · Original source · commit fc91b91ddc367830b755b215dbc69669675ad6a0
Technical metadata and extraction receipts
Stable ID: use-case-summary-binder-20261022
- field
- summary
- reason
- Draft the use case's summary for the 2026-10-22 evidence pass (#176).
- review
- artifact sha256: 953b35644c0fa06ff090d7614c2e19525831f8fde50242e176d54474133c5a42; method: source-hash-verification; independent-cell-check; ai-assisted-source-review; method note: Re-downloaded with curl (HTTP 200, 12,333,400 bytes) and the SHA-256 recomputed and matched. Own text layer made with pdftotext -layout (poppler 26.08.0), reproducing the extraction pass's 2,811 lines. Table 1, Table S2, Table S3 and Sections S1.2.1, S2, S4.1 and S4.2 read cell by cell and compared with every record. Column assignment re-derived arithmetically rather than trusted.; note: Reviewed in docs/reviews/use-cases/binder-2026-10-22.md. Automated AI review of the source transcription only; it is not human scientific review and nothing here was reproduced experimentally.; retrieval url: https://arxiv.org/pdf/2409.08022v1; reviewed at: 2026-10-22T15:00:00Z; reviewer: claude; reviewer note: Claude review agent, independent of the extraction agent; no human review claimed
- revision
- 1
- source locator
- AlphaProteo Table 1, Table S2 and Sections S1.2.1, S2 and S4.1; BindCraft Introduction and Results prose; Bennett Supplementary Methods Table 6; Adaptyv Sections 2.3, 2.4, 3.1, 3.2, 4.1, 4.2 and 4.3
- value
- Four studies, pinned here as seven artifacts, carry measured outcomes for de novo binder design, and none of them answers which workflow to use, because no paper runs two design methods and a conventional comparator on the same targets with one assay and one hit definition. The literature pass behind this evidence found nine candidate sources with measured outcomes; the five that were not retrieved are recorded as gaps rather than as evidence of what they would show. What the measured evidence shows is that the target matters more than the method. AlphaProteo's yeast-display success rate across eight targets runs from 0% over 54 designs on TNF-alpha to 88% over 94 designs on BHRF1, at a binding-signal threshold of 0.2 (1.3 on IL-17A). BindCraft reports an average experimental success rate of 46.3% over twelve targets with a range of 10% to 100%, built from per-target counts as small as 2 binders from 7 designs on Bet v1 and as large as 6 from 6 on the SpCas9 REC1 domain. The same family of methods applied to antibody variable domains is two orders of magnitude worse: fine-tuned RFdiffusion gives 2% over 96 designs on TcdB, 0% over 96 on IL-7 receptor alpha, and 0.01% to 0.2% over 9,000 designs per target by yeast display. On influenza H1 stem the same design campaign gives 1% over 96 designs by SPR and 0.2% over 9,000 by display, so the screening method moves the rate as much as the target does. Nearly all of this is author-reported by the group that built the method, which also chose the targets, ran the assay and chose which designs to test. The exception is the Adaptyv EGFR competition, where a third-party laboratory expressed and measured designs from many entrants on one target and one assay: 2.5% of 201 round-1 designs bound (printed elsewhere in the same paper as 3%), and 53 of 400 round-2 designs bound, printed as 13%. That source cannot be turned into a per-method rate: design methods are the entrants' own declarations, the organisers hand-picked 101 of 201 round-1 and 300 of 400 round-2 designs for diversity, and the three binding thresholds behind the figure counts are never defined. Affinities reached are better than the hit rates suggest. AlphaProteo's best measured binder was 0.082 nM on IL-7 receptor alpha by HTRF; BindCraft's best ranged from 5 nM on CbAgo to 5.7 micromolar on CrSAS-6; the best de novo design in the Adaptyv competition reached 82 nM and the winning optimised cetuximab fragment 1.21 nM, against 9.94 nM for the cetuximab positive control measured on the same instrument. Three things stop these numbers from ranking methods. The hit definitions are different endpoints, not different thresholds on one endpoint. The denominators are small and chosen, and the designs tested are the top picks of each method's own filter, so design and selection are coupled: changing only AlphaProteo's filter moved its PD-L1 rate from 9.6% over 94 designs to 16.1% over 31, and the Bennett authors attribute their low antibody rates partly to a filter they describe as weak. And the spread within one method across targets is wider than any plausible difference between methods. No conventional comparator is run anywhere in this evidence, so there is no measurement of what a designed binder is being compared against.
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