FEP+ protocol tuned per system after seeing the error against experiment
Limitation of FEP+ with per-system manual protocol adjustment
The Boltz-2 supplement states that 'The results of FEP+ are intended to show the maximum attainable accuracy of current (commercial) FEP simulations by manually adjusting the protocol (input preparation, perturbation map, force field) to the system at hand after observing the error with respect to the experiment [Ross et al., 2023]'. Ross et al. 2023 describes the same adjustments in its own words: extra rotamer states, protonation states, atom mappings and scaled torsions were added 'from visual inspection and manual intervention' when poor sampling was observed in prior simulations.
Limit the Boltz-2 supplement states about the FEP+ arm it compares against.
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.
12 evidence rows matching the loaded filters
| Property and statement | Original source and location | Review and provenance |
|---|---|---|
| Claimed field limitation Context-only references | Boltz-2: Towards Accurate and Efficient Binding Affinity Prediction, supplementary appendix Boltz-2 supplement appendix D.2.2, 'Baselines'; Ross et al. 2023 Results, 'Using FEP to resolve ambiguities in the structural inputs' Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: bioRxiv v1 posted 2025-06-18; supplement PDF as deposited in Europe PMC PMC12262699 (PPR1038344) | not individually reviewed No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: The recorded hash is of the supplement PDF itself, extracted from the Europe PMC supplementaryFiles ZIP (ZIP SHA-256 25050dabd9c66fdb955704095023037f1bbabc3a93b7b61f00344c75df8bdb70 on 2026-10-22; the ZIP is rebuilt per request and its hash is not stable). Archive member: NIHPP2025.06.14.659707v1-supplement-1.pdf |
| Claimed field limitation Context-only references | The maximal and current accuracy of rigorous protein-ligand binding free energy calculations Boltz-2 supplement appendix D.2.2, 'Baselines'; Ross et al. 2023 Results, 'Using FEP to resolve ambiguities in the structural inputs' Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: Communications Chemistry 6:222 (2023); Europe PMC full-text XML snapshot PMC10576784 | not individually reviewed No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: Hash scope not separately documented; inspect source record |
| Source location Boltz-2 supplement appendix D.2.2, 'Baselines'; Ross et al. 2023 Results, 'Using FEP to resolve ambiguities in the structural inputs' Context-only references | Boltz-2: Towards Accurate and Efficient Binding Affinity Prediction, supplementary appendix Boltz-2 supplement appendix D.2.2, 'Baselines'; Ross et al. 2023 Results, 'Using FEP to resolve ambiguities in the structural inputs' Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: bioRxiv v1 posted 2025-06-18; supplement PDF as deposited in Europe PMC PMC12262699 (PPR1038344) | not individually reviewed No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: The recorded hash is of the supplement PDF itself, extracted from the Europe PMC supplementaryFiles ZIP (ZIP SHA-256 25050dabd9c66fdb955704095023037f1bbabc3a93b7b61f00344c75df8bdb70 on 2026-10-22; the ZIP is rebuilt per request and its hash is not stable). Archive member: NIHPP2025.06.14.659707v1-supplement-1.pdf |
| Source location Boltz-2 supplement appendix D.2.2, 'Baselines'; Ross et al. 2023 Results, 'Using FEP to resolve ambiguities in the structural inputs' Context-only references | The maximal and current accuracy of rigorous protein-ligand binding free energy calculations Boltz-2 supplement appendix D.2.2, 'Baselines'; Ross et al. 2023 Results, 'Using FEP to resolve ambiguities in the structural inputs' Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: Communications Chemistry 6:222 (2023); Europe PMC full-text XML snapshot PMC10576784 | not individually reviewed No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: Hash scope not separately documented; inspect source record |
| Claimed value The Boltz-2 supplement states that 'The results of FEP+ are intended to show the maximum attainable accuracy of current (commercial) FEP simulations by manually adjusting the protocol (input preparation, perturbation map, force field) to the system at hand after observing the error with respect to the experiment [Ross et al., 2023]'. Ross et al. 2023 describes the same adjustments in its own words: extra rotamer states, protonation states, atom mappings and scaled torsions were added 'from visual inspection and manual intervention' when poor sampling was observed in prior simulations. Context-only references | Boltz-2: Towards Accurate and Efficient Binding Affinity Prediction, supplementary appendix Boltz-2 supplement appendix D.2.2, 'Baselines'; Ross et al. 2023 Results, 'Using FEP to resolve ambiguities in the structural inputs' Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: bioRxiv v1 posted 2025-06-18; supplement PDF as deposited in Europe PMC PMC12262699 (PPR1038344) | not individually reviewed No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: The recorded hash is of the supplement PDF itself, extracted from the Europe PMC supplementaryFiles ZIP (ZIP SHA-256 25050dabd9c66fdb955704095023037f1bbabc3a93b7b61f00344c75df8bdb70 on 2026-10-22; the ZIP is rebuilt per request and its hash is not stable). Archive member: NIHPP2025.06.14.659707v1-supplement-1.pdf |
| Claimed value The Boltz-2 supplement states that 'The results of FEP+ are intended to show the maximum attainable accuracy of current (commercial) FEP simulations by manually adjusting the protocol (input preparation, perturbation map, force field) to the system at hand after observing the error with respect to the experiment [Ross et al., 2023]'. Ross et al. 2023 describes the same adjustments in its own words: extra rotamer states, protonation states, atom mappings and scaled torsions were added 'from visual inspection and manual intervention' when poor sampling was observed in prior simulations. Context-only references | The maximal and current accuracy of rigorous protein-ligand binding free energy calculations Boltz-2 supplement appendix D.2.2, 'Baselines'; Ross et al. 2023 Results, 'Using FEP to resolve ambiguities in the structural inputs' Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: Communications Chemistry 6:222 (2023); Europe PMC full-text XML snapshot PMC10576784 | not individually reviewed No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: Hash scope not separately documented; inspect source record |
| Description Limit the Boltz-2 supplement states about the FEP+ arm it compares against. Context-only references | Boltz-2: Towards Accurate and Efficient Binding Affinity Prediction, supplementary appendix Boltz-2 supplement appendix D.2.2, 'Baselines'; Ross et al. 2023 Results, 'Using FEP to resolve ambiguities in the structural inputs' Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: bioRxiv v1 posted 2025-06-18; supplement PDF as deposited in Europe PMC PMC12262699 (PPR1038344) | not individually reviewed No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: The recorded hash is of the supplement PDF itself, extracted from the Europe PMC supplementaryFiles ZIP (ZIP SHA-256 25050dabd9c66fdb955704095023037f1bbabc3a93b7b61f00344c75df8bdb70 on 2026-10-22; the ZIP is rebuilt per request and its hash is not stable). Archive member: NIHPP2025.06.14.659707v1-supplement-1.pdf |
| Description Limit the Boltz-2 supplement states about the FEP+ arm it compares against. Context-only references | The maximal and current accuracy of rigorous protein-ligand binding free energy calculations Boltz-2 supplement appendix D.2.2, 'Baselines'; Ross et al. 2023 Results, 'Using FEP to resolve ambiguities in the structural inputs' Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: Communications Chemistry 6:222 (2023); Europe PMC full-text XML snapshot PMC10576784 | not individually reviewed No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: Hash scope not separately documented; inspect source record |
| Relationship: subject uc-leadopt-20261022-config-fep-plus Context-only references | Boltz-2: Towards Accurate and Efficient Binding Affinity Prediction, supplementary appendix Boltz-2 supplement appendix D.2.2, 'Baselines'; Ross et al. 2023 Results, 'Using FEP to resolve ambiguities in the structural inputs' Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: bioRxiv v1 posted 2025-06-18; supplement PDF as deposited in Europe PMC PMC12262699 (PPR1038344) | not individually reviewed No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: The recorded hash is of the supplement PDF itself, extracted from the Europe PMC supplementaryFiles ZIP (ZIP SHA-256 25050dabd9c66fdb955704095023037f1bbabc3a93b7b61f00344c75df8bdb70 on 2026-10-22; the ZIP is rebuilt per request and its hash is not stable). Archive member: NIHPP2025.06.14.659707v1-supplement-1.pdf |
| Relationship: subject uc-leadopt-20261022-config-fep-plus Context-only references | The maximal and current accuracy of rigorous protein-ligand binding free energy calculations Boltz-2 supplement appendix D.2.2, 'Baselines'; Ross et al. 2023 Results, 'Using FEP to resolve ambiguities in the structural inputs' Shared locator for this statement’s cited sources; not a separate locator for each citation. Version: Communications Chemistry 6:222 (2023); Europe PMC full-text XML snapshot PMC10576784 | not individually reviewed No individual claim review recorded Audit detailsField: Source artifact SHA-256: Hash scope: Hash scope not separately documented; inspect source record |
Sources and history
Release 2026-10-22-1b7cf027e4f6 · Record review: source checked
2 source records and release history
- Boltz-2: Towards Accurate and Efficient Binding Affinity Prediction, supplementary appendix · Original source · bioRxiv v1 posted 2025-06-18; supplement PDF as deposited in Europe PMC PMC12262699 (PPR1038344)
- The maximal and current accuracy of rigorous protein-ligand binding free energy calculations · Original source · Communications Chemistry 6:222 (2023); Europe PMC full-text XML snapshot PMC10576784
Technical metadata and extraction receipts
Stable ID: uc-leadopt-20261022-claim-fep-plus-tuned
- field
- limitation
- value
- The Boltz-2 supplement states that 'The results of FEP+ are intended to show the maximum attainable accuracy of current (commercial) FEP simulations by manually adjusting the protocol (input preparation, perturbation map, force field) to the system at hand after observing the error with respect to the experiment [Ross et al., 2023]'. Ross et al. 2023 describes the same adjustments in its own words: extra rotamer states, protonation states, atom mappings and scaled torsions were added 'from visual inspection and manual intervention' when poor sampling was observed in prior simulations.
- source locator
- Boltz-2 supplement appendix D.2.2, 'Baselines'; Ross et al. 2023 Results, 'Using FEP to resolve ambiguities in the structural inputs'
- review
- method: source-hash-verification; pdf-text-parse; independent-cell-check; rendered-source-visual-check; ai-assisted-source-review; method note: Re-retrieved all three sources and matched each pinned SHA-256. Re-rendered the Boltz-2 supplement with pdftotext -layout (poppler 26.08.0) and matched the text layer's recorded SHA-256. Re-read all 256 cells with a parser written for this review that does not import the extraction script, matching each result to its cell through its own source_locator, and separately read appendix tables 11, 12 and 14 from PNG renderings of PDF pages 29 and 30 at 160 dpi, and Ross Table 3 from the pinned XML markup. Checked printed value, numeric value, locator, metric concept, qualifier, direction, unit, uncertainty and the linked configuration, protocol and dataset, and that every N/A or '-' cell is recorded as missing with a reason.; reviewer: claude; reviewer note: Claude review agent, independent of the extraction agent; no human review claimed; reviewed at: 2026-10-22T13:40:00Z; artifact sha256: be867a5d92add8b223d47d882a4213ad489741f3e4d5081a0901a54370342569; retrieval url: https://www.ebi.ac.uk/europepmc/webservices/rest/PMC12262699/supplementaryFiles; note: Independent review 2026-10-22: the quoted wording was matched against the pinned artifact and the locator checked.