{"atlas_id":"pmmr-mucinous-colon","records":[{"allowed_modifications":[],"claim_ceiling":"completed computational geometry-recovery screen with no promoted generated candidate","constraints":["Retain both target chains A and B in every generated complex.","Use the beta-6 hotspot set from the hash-bound interface artifact.","Score recovery against the complete deposited A/B target footprint as well as the beta-6 conditioning subset.","Reject outputs that do not contact the locked beta-6 site."],"controls":{"negative":["the same target preparation with hotspot conditioning removed","a size-matched off-site beta-6 surface patch"],"positive":["RCSB 8TCG deposited B6_BP_dslf chain C interface"]},"desired_effect":"Recover the deposited B6_BP_dslf footprint as a target-conditioned positive control for the structure-to-design lane.","evidence_refs":["RCSB:8TCG","DOI:10.1038/s41467-023-41272-z"],"format_options":[{"format":"miniprotein","length_range":[55,95],"suitability":"preferred"}],"job_parameters":{},"method_posture":"deposited-complex-evaluation","molecular_job":"block","opportunity_id":"O-ITGB6-8TCG-REFERENCE-RECOVERY","principal_risks":["A recovered reference footprint validates geometric conditioning and transport; it does not establish binding affinity, selectivity, or therapeutic activity.","The beta-6 conditioning subset represents an interface that also contacts alpha-v chain A."],"rationale":"The deposited target-minibinder complex supplies an exact public reference geometry for testing target preparation, conditioning, artifact transport, and interface recovery before disease-opportunity fan-out.","reference_interface_registration":{"registered_at":"2026-09-04","registrar":"register_reference_interface.py","registration_spec":{"bytes":5131,"name":"8tcg-reference-interface.registration.json","sha256":"1f314a010b5b8182d2fc4df4785685501d3b2d53643d1ade2e34bd7c9c1beaa6"}},"requested_delivered_count":8,"required_outputs":["candidate-fasta","target-binder-mmcif","site-aware-metrics-json","candidate-lineage-json","provider-native-receipts","white-background-structure-render"],"result_ingestion":{"candidate_count":16,"cofold_observation_count":18,"contract":"demos/pmmr-mucinous-colon/campaigns/8tcg-itgav-itgb6-geometry-recovery/result-ingest.plan.json","control_calibration_status":"passed","normalized_collection":"binder-results.json","normalized_collection_sha256":"46411b9e141e3f74534b329341bcb20dd246aff19330fdd04ecbf794a3bc02b0","normalized_collection_storage":"external-artifact-root","promoted_candidate_count":0,"result_state":"partial","state":"partial-stop-gate-fired","stop_reason":"No generated candidate passed the frozen reference-site geometry gate; finalist rescore was not launched.","validated_backbone_count":8,"validated_inputs":["RFdiffusion3 target-chain remap and fixed-target geometry","ProteinMPNN candidate sequence, parent-backbone identity, receipt, and FASTA record","Boltz scored or failed observation with hash-bound complex, PAE, metric source, and design pose"]},"selected_format":"miniprotein","site":{"campaign_site_lock_id":"SITE-8TCG-BETA6-REFERENCE","evidence":"Ten beta-6 residues were selected deterministically from the heavy-atom contact network observed between target chains A/B and deposited minibinder chain C in RCSB 8TCG. The complete 33-residue target footprint and all 60 residue contact pairs remain in the interface artifact.","evidence_class":"experimental-reference-binder-interface","excluded_regions":["deposited minibinder chain C","nonpolymer glycans and metal ions in the RFdiffusion3 compatibility input"],"full_observed_target_interface_residue_count":33,"mode":"reference-interface","numbering_scheme":"RCSB author numbering mapped to sequential campaign numbering per target chain","reference_interface_id":"IF-RCSB-8TCG-AB-C","residues":[{"author_residue_number":"183","campaign_chain_id":"B","campaign_residue_number":71,"insertion_code":null},{"author_residue_number":"126","campaign_chain_id":"B","campaign_residue_number":14,"insertion_code":null},{"author_residue_number":"219","campaign_chain_id":"B","campaign_residue_number":107,"insertion_code":null},{"author_residue_number":"129","campaign_chain_id":"B","campaign_residue_number":17,"insertion_code":null},{"author_residue_number":"221","campaign_chain_id":"B","campaign_residue_number":109,"insertion_code":null},{"author_residue_number":"218","campaign_chain_id":"B","campaign_residue_number":106,"insertion_code":null},{"author_residue_number":"127","campaign_chain_id":"B","campaign_residue_number":15,"insertion_code":null},{"author_residue_number":"316","campaign_chain_id":"B","campaign_residue_number":204,"insertion_code":null},{"author_residue_number":"220","campaign_chain_id":"B","campaign_residue_number":108,"insertion_code":null},{"author_residue_number":"217","campaign_chain_id":"B","campaign_residue_number":105,"insertion_code":null}],"source_actionable_site_id":"SITE-RCSB-8TCG-b6-bp-dslf-miniprotein","uncertain_regions":["alpha-v chain A contributes 11 observed interface residues but is retained as receptor context rather than a conditioning-hotspot chain"]},"site_id":"SITE-RCSB-8TCG-b6-bp-dslf-miniprotein","structure_id":"S-RCSB-8TCG-RFD3-AB","target_id":"T-ENSG00000115221"},{"desired_effect":"Record the completed FAP/6Y0F charge-aware docking screen as a hypothesis-generation handoff; do not infer affinity or inhibition.","method_posture":"completed-defined-pocket-computational-screening","molecular_job":"defined-pocket small-molecule screening handoff","opportunity_id":"O-FAP-6Y0F-DEFINED-POCKET-SCREEN-HANDOFF","principal_risks":["Docking scores and pose geometry are computational hypotheses only.","The five confirmation passers retain reactivity, aggregation, solubility, and assay-interference review flags where recorded.","No measured binding, target engagement, or disease efficacy is established."],"rationale":"The deposited linagliptin pocket supplied a locked extracellular FAP chain-A control and passed the unchanged redocking gate after charge-aware receptor preparation.","screen_handoff":{"binder_promotions":0,"claim_ceiling":"computational-screening-hypothesis","computational_screening_hypotheses":24,"confirmation_plan_sha256":"ea69040c2b09aafa310673c94bc8adbeec3b3709b6f563864d65e5aadb6a20c0","geometry_and_same_protocol_repeatability_passers":["NP011","NP004","NP015","NP021","NP001"],"outcome":"completed-control-qualified","run_id":"fap-6y0f-defined-pocket-screen-v1","run_manifest_sha256":"02cf4d95cb5cb350bc2753299af01b874f00ec56a350d09d356dd500322a0029","screen_id":"FAP-6Y0F-356-smina-v1"},"site_id":"SITE-RCSB-6Y0F-linagliptin","structure_id":"S-RCSB-6Y0F","target_id":"T-ENSG00000078098"},{"desired_effect":"Record the completed CD73/9R0G screen as a computational pose-ranking hypothesis handoff with its metal-contact control evidence.","method_posture":"completed-defined-pocket-computational-screening","molecular_job":"defined-pocket small-molecule screening handoff","opportunity_id":"O-NT5E-9R0G-DEFINED-POCKET-SCREEN-HANDOFF","principal_risks":["The legacy Smina preparation and score are not affinity or inhibition measurements.","A prior tracked canary-failure interpretation is retained as superseded evidence, not erased.","No measured binder or therapeutic claim follows from the five confirmation passers."],"rationale":"The deposited A1JCG control passed the initial and confirmation pose checks for geometry and metal contact.","screen_handoff":{"binder_promotions":0,"claim_ceiling":"computational-screening-hypothesis","computational_screening_hypotheses":24,"confirmation_plan_sha256":"279365e276263d2f02dfc80d2eb898d6c6f46df7e7df3495dfc25f657fa18c6b","geometry_and_same_protocol_repeatability_passers":["NP011","NP005","NP015","NP013","NP012"],"outcome":"completed-control-qualified; prior canary-failure tracking claim superseded by output-grounded validation","run_id":"nt5e-9r0g-defined-pocket-screen-v1","run_manifest_sha256":"53b5485438a3478ff509c7ac62f9506251a70d83e1d00295a67f9d98178ae0bd","screen_id":"NT5E-9R0G-A1JCG-smina-v1"},"site_id":"SITE-RCSB-9R0G-cd73-compound-21","structure_id":"S-RCSB-9R0G","target_id":"T-ENSG00000135318"},{"checkpoint_handoff":{"binder_promotions":0,"candidate_geometry_passers_before_control_stop":["ceacam5-cp3-boltzgen-03","ceacam5-cp3-pxdesign-proteinmpnn-03"],"checkpoint_id":"ceacam5-8bw0-three-arm-checkpoint","checkpoint_outcome_sha256":"a98161f80425a6c93053cacb87b8edd319674355c106919aea21bc1866f5bf30","claim_ceiling":"computational-candidate-hypothesis","control_gate_passed":false,"control_gate_reasons":["positive-ipsae-floor","footprint-margin"],"outcome":"executed-stop-gate-control-failure"},"desired_effect":"Preserve the executed CEACAM5 A3-B3 checkpoint stop as an explicit non-promotion decision.","method_posture":"executed-control-failed-checkpoint","molecular_job":"three-arm protein-binder checkpoint handoff","opportunity_id":"O-CEACAM5-8BW0-THREE-ARM-CHECKPOINT-HANDOFF","principal_risks":["Two generated candidates passed the candidate geometry gate before the control stop; they are not promoted binders.","The checkpoint does not settle the independent four-arm campaign.","No binding, selectivity, or therapeutic activity was established."],"rationale":"The three-arm comparison completed six predictions and local remeasurement. The positive control failed the interface-score and contact-margin requirements.","site_id":"SITE-RCSB-8BW0-tusamitamab-fab","structure_reference_id":"S-RCSB-8BW0","target_id":"T-ENSG00000105388"},{"campaign_handoff":{"binder_promotions":0,"campaign_id":"ceacam5-8bw0-multigenerator","campaign_outcome_sha256":"2df0256aaaee71c25d6e10a23de42d6225ecfe63bf12dd0bd2b6ef8f26cfd889","claim_ceiling":"computational-candidate-hypothesis","freebindcraft_returned_candidate_count":0,"local_geometry_pass_count":4,"local_geometry_rollup_sha256":"d8f6e7bfc3d44667e5f320fa8d74a1dde9df43fcb310f17a0751aa21c0c8a44b","returned_candidate_count":9},"desired_effect":"Preserve the original four-arm campaign as a completed partial result with an explicit incomplete-cohort stop.","method_posture":"executed-stop-incomplete-four-arm-cohort","molecular_job":"four-arm protein-binder comparison","opportunity_id":"O-CEACAM5-8BW0-FOUR-ARM-OUTCOME","principal_risks":["The four local geometry passers have no common independent score in this campaign and are not promoted.","FreeBindCraft produced no scored candidate because the prediction service failed.","The separate three-arm checkpoint does not retroactively complete this four-arm comparison."],"rationale":"Three routes returned nine 64-residue candidates and four passed the frozen local geometry gate. FreeBindCraft returned no candidate, so the locked four-arm join and common screen could not be formed.","site_id":"SITE-RCSB-8BW0-tusamitamab-fab","structure_reference_id":"S-RCSB-8BW0","target_id":"T-ENSG00000105388"},{"desired_effect":"Test whether a paired tusamitamab VH/VL control context resolves the single-domain control ambiguity before any further CEACAM5 binder qualification.","diagnostic_handoff":{"binder_promotions":0,"campaign_id":"ceacam5-8bw0-paired-fv-context-diagnostic","claim_ceiling":"paired-variable-domain-context-control-diagnostic","diagnostic_outcome_sha256":"c0cff32084c2f5a030bdda3dfc89afe9b8fb7dad1a0f96816bca1643b1f0f860","observed_union_full_footprint_contacts":12,"observed_union_full_footprint_residue_count":17,"observed_union_target_recovery_rmsd_angstrom":2.1726,"report_handoff_sha256":"72f9d08fc68ec10f46440638ccffdb5b84e44e7b42504375496171e05fef02c2","scorer_compatible":false},"method_posture":"executed-bounded-diagnostic-stopped-on-scorer-incompatibility","molecular_job":"paired variable-domain context diagnostic","opportunity_id":"O-CEACAM5-8BW0-PAIRED-FV-DIAGNOSTIC","principal_risks":["The scorer lacked the residue map required for a three-chain iPSAE calculation.","The observed union of chains B and C is a context diagnostic and not a promotable binder candidate.","No binding, selectivity, pharmacology, or therapeutic activity was established."],"rationale":"The deposited CEACAM5 Fab footprint spans paired variable domains. One bounded paired-context observation was issued to diagnose the control surface without treating the output as a designed therapeutic candidate.","site_id":"SITE-RCSB-8BW0-tusamitamab-fab","structure_reference_id":"S-RCSB-8BW0","target_id":"T-ENSG00000105388"},{"campaign_handoff":{"binder_promotions":0,"campaign_id":"ceacam5-8bw0-replacement-generators-20260904","campaign_outcome_sha256":"5356c67f95caf227d74f35e113e79ce7b174f61794ffd8b19e9cb18b368e983e","claim_ceiling":"computational-screening-hypothesis","esmfold2_candidate_count":3,"esmfold2_geometry_pass_count":0,"external_final_summary_sha256":"ace5d509f41dfb566aaa49240fe231eddafa1b8d80fad6fe58e95cfd89acd78f","genie3_candidate_count":1,"genie3_site_contacts_full":16,"genie3_site_contacts_vh_subsite":10,"genie3_target_recovery_limit_angstrom":0.001,"genie3_target_recovery_rmsd_angstrom":0.022359168},"desired_effect":"Evaluate bounded Genie3 site-conditioned and ESMFold2 unconditioned replacement-generator routes under the frozen CEACAM5 target-recovery and site-contact gates.","method_posture":"executed-bounded-replacement-generator-comparison-no-promotion","molecular_job":"replacement structure-generator comparison","opportunity_id":"O-CEACAM5-8BW0-REPLACEMENT-GENERATOR-OUTCOME","principal_risks":["The Genie3 trace recovered the requested site footprint but failed the frozen target-coordinate lock, so sequence filling and scale generation were not allowed.","ESMFold2 was unconditioned and generated exploratory folds rather than target-site-conditioned binders; all three failed the frozen site-contact gate.","None of the four structures was promoted or shown to bind CEACAM5."],"rationale":"The replacement campaign tested whether fast cloud generators could recover the locked tusamitamab extracellular footprint after FreeBindCraft produced no promotable artifact, while preserving explicit route limitations and stop gates.","site_id":"SITE-RCSB-8BW0-tusamitamab-fab","structure_id":"S-RCSB-8BW0","target_id":"T-ENSG00000105388"}],"schema_version":"codex-surface-opportunity-collection/v0.1"}