{ "schema": "dia-health-one.nnc2215-linker-mapping-audit.v1", "run": { "run_id": "DHO-NNC2215-LINK-MAP-20261018T061903Z", "created_at_utc": "2026-10-18T06:19:03.100786+00:00", "script": "research/audit_nnc2215_linker_mapping.py", "script_sha256": "777194a5369b4a30d5a44016c1730967e7b259dcd2a532ec5e2be0c6f52b0ac0", "nvidia_gpu_used": false }, "sources": { "paper_doi": "10.1038/s41586-024-08042-3", "figure_7a_b29_alkyne_linker_url": "https://media.springernature.com/original/springer-static/esm/art%3A10.1038%2Fs41586-024-08042-3/MediaObjects/41586_2024_8042_Fig12_ESM.jpg", "figure_8i_macrocycle_roof_propyl_azide_url": "https://media.springernature.com/original/springer-static/esm/art%3A10.1038%2Fs41586-024-08042-3/MediaObjects/41586_2024_8042_Fig13_ESM.jpg", "figure_caption_evidence": "Figure 7a numbers carbons 3\u20138 in O-succinimidyl pentyn-1-oxycarbonyl; Figure 8i numbers the macrocycle roof propyl-azide chain carbons 21\u201323.", "source_b29_linker_formula_after_nhs_departure": "C6H6O2", "source_macrocycle_roof_propyl_azide_formula": "C56H63N15O12", "expected_b29_attachment_heavy_elements_after_click": { "C": 62, "N": 15, "O": 14 } }, "states": [ { "state": "active_open", "model_file": "structures/nnc2215-open-model.pdb", "sha256": "44c29d45b28ace4ede73a75a8e076dbca62e14b34bd3938a4b495ebd1270267a", "candidate_source_to_model_atom_map": { "insulin_lys_b29_nz": { "pdb_atom": { "name": "NZ", "residue": "LYS", "chain": "B", "residue_number": "29", "element": "N" }, "serial": 480 }, "source_b29_carbon_3_carbonyl": { "pdb_atom": { "name": "CD1", "residue": "LYX", "chain": "B", "residue_number": "30", "element": "C" }, "serial": 497 }, "source_b29_carbon_4": { "pdb_atom": { "name": "CD2", "residue": "LYX", "chain": "B", "residue_number": "30", "element": "C" }, "serial": 498 }, "source_b29_carbon_5": { "pdb_atom": { "name": "C1", "residue": "LYX", "chain": "B", "residue_number": "30", "element": "C" }, "serial": 505 }, "source_b29_carbon_6": { "pdb_atom": { "name": "C2", "residue": "LYX", "chain": "B", "residue_number": "30", "element": "C" }, "serial": 506 }, "source_b29_carbon_7_alkyne": { "pdb_atom": { "name": "CD3", "residue": "LYX", "chain": "B", "residue_number": "30", "element": "C" }, "serial": 499 }, "source_b29_carbon_8_alkyne": { "pdb_atom": { "name": "CD4", "residue": "LYX", "chain": "B", "residue_number": "30", "element": "C" }, "serial": 500 }, "source_macrocycle_c21_candidate": { "pdb_atom": { "name": "C31", "residue": "MC", "chain": "C", "residue_number": "1", "element": "C" }, "serial": 861 }, "source_macrocycle_c22_candidate": { "pdb_atom": { "name": "CD6", "residue": "LYX", "chain": "B", "residue_number": "30", "element": "C" }, "serial": 502 }, "source_macrocycle_c23_candidate": { "pdb_atom": { "name": "CD5", "residue": "LYX", "chain": "B", "residue_number": "30", "element": "C" }, "serial": 501 }, "source_azide_n_attached_to_c23_candidate": { "pdb_atom": { "name": "ND3", "residue": "LYX", "chain": "B", "residue_number": "30", "element": "N" }, "serial": 496 }, "source_macrocycle_ring_anchor_candidate": { "pdb_atom": { "name": "C71", "residue": "MC", "chain": "C", "residue_number": "1", "element": "C" }, "serial": 901 }, "source_b29_carbonyl_oxygen": { "pdb_atom": { "name": "OD", "residue": "LYX", "chain": "B", "residue_number": "30", "element": "O" }, "serial": 503 }, "source_b29_oxygen_link": { "pdb_atom": { "name": "O1", "residue": "LYX", "chain": "B", "residue_number": "30", "element": "O" }, "serial": 504 }, "source_triazole_n1_candidate": { "pdb_atom": { "name": "ND1", "residue": "LYX", "chain": "B", "residue_number": "30", "element": "N" }, "serial": 494 }, "source_triazole_n2_candidate": { "pdb_atom": { "name": "ND2", "residue": "LYX", "chain": "B", "residue_number": "30", "element": "N" }, "serial": 495 } }, "candidate_adjacency_edges_verified": 16, "candidate_adjacency_edges_missing": [], "observed_element_counts_by_model_residue": { "LYX": { "C": 8, "H": 11, "N": 3, "O": 2 }, "MC": { "C": 56, "H": 60, "N": 12, "O": 12 } }, "observed_b29_pool_heavy_elements": { "C": 64, "N": 15, "O": 14 }, "source_b29_pool_heavy_elements": { "C": 62, "N": 15, "O": 14 }, "observed_minus_source_heavy_element_delta": { "C": 2 }, "candidate_macrocycle_partition": { "source_macrocycle_c21_c23_tail_atoms": 3, "candidate_tail_atoms_in_lyx": 2, "candidate_tail_atom_in_mc": 1, "source_macrocycle_carbons_expected_in_mc_after_split": 54, "observed_mc_carbon_records": 56, "candidate_mc_carbon_excess": 2 } }, { "state": "inactive_closed", "model_file": "structures/nnc2215-closed-model.pdb", "sha256": "a8287b859e73b274e8403ee56cd83564bc30fd0503d852829fa805fdc777e12d", "candidate_source_to_model_atom_map": { "insulin_lys_b29_nz": { "pdb_atom": { "name": "NZ", "residue": "LYS", "chain": "B", "residue_number": "29", "element": "N" }, "serial": 794 }, "source_b29_carbon_3_carbonyl": { "pdb_atom": { "name": "CD1", "residue": "LYX", "chain": "B", "residue_number": "30", "element": "C" }, "serial": 812 }, "source_b29_carbon_4": { "pdb_atom": { "name": "CD2", "residue": "LYX", "chain": "B", "residue_number": "30", "element": "C" }, "serial": 813 }, "source_b29_carbon_5": { "pdb_atom": { "name": "C1", "residue": "LYX", "chain": "B", "residue_number": "30", "element": "C" }, "serial": 820 }, "source_b29_carbon_6": { "pdb_atom": { "name": "C2", "residue": "LYX", "chain": "B", "residue_number": "30", "element": "C" }, "serial": 821 }, "source_b29_carbon_7_alkyne": { "pdb_atom": { "name": "CD3", "residue": "LYX", "chain": "B", "residue_number": "30", "element": "C" }, "serial": 814 }, "source_b29_carbon_8_alkyne": { "pdb_atom": { "name": "CD4", "residue": "LYX", "chain": "B", "residue_number": "30", "element": "C" }, "serial": 815 }, "source_macrocycle_c21_candidate": { "pdb_atom": { "name": "C31", "residue": "MC", "chain": "C", "residue_number": "1", "element": "C" }, "serial": 862 }, "source_macrocycle_c22_candidate": { "pdb_atom": { "name": "C", "residue": "LYX", "chain": "B", "residue_number": "30", "element": "C" }, "serial": 817 }, "source_macrocycle_c23_candidate": { "pdb_atom": { "name": "CD5", "residue": "LYX", "chain": "B", "residue_number": "30", "element": "C" }, "serial": 816 }, "source_azide_n_attached_to_c23_candidate": { "pdb_atom": { "name": "ND3", "residue": "LYX", "chain": "B", "residue_number": "30", "element": "N" }, "serial": 811 }, "source_macrocycle_ring_anchor_candidate": { "pdb_atom": { "name": "C71", "residue": "MC", "chain": "C", "residue_number": "1", "element": "C" }, "serial": 902 }, "source_b29_carbonyl_oxygen": { "pdb_atom": { "name": "O", "residue": "LYX", "chain": "B", "residue_number": "30", "element": "O" }, "serial": 818 }, "source_b29_oxygen_link": { "pdb_atom": { "name": "O1", "residue": "LYX", "chain": "B", "residue_number": "30", "element": "O" }, "serial": 819 }, "source_triazole_n1_candidate": { "pdb_atom": { "name": "ND1", "residue": "LYX", "chain": "B", "residue_number": "30", "element": "N" }, "serial": 809 }, "source_triazole_n2_candidate": { "pdb_atom": { "name": "ND2", "residue": "LYX", "chain": "B", "residue_number": "30", "element": "N" }, "serial": 810 } }, "candidate_adjacency_edges_verified": 16, "candidate_adjacency_edges_missing": [], "observed_element_counts_by_model_residue": { "LYX": { "C": 8, "H": 10, "N": 3, "O": 2 }, "MC": { "C": 56, "H": 60, "N": 12, "O": 12 } }, "observed_b29_pool_heavy_elements": { "C": 64, "N": 15, "O": 14 }, "source_b29_pool_heavy_elements": { "C": 62, "N": 15, "O": 14 }, "observed_minus_source_heavy_element_delta": { "C": 2 }, "candidate_macrocycle_partition": { "source_macrocycle_c21_c23_tail_atoms": 3, "candidate_tail_atoms_in_lyx": 2, "candidate_tail_atom_in_mc": 1, "source_macrocycle_carbons_expected_in_mc_after_split": 54, "observed_mc_carbon_records": 56, "candidate_mc_carbon_excess": 2 } } ], "assessment": { "candidate_b29_linker_mapping_supported_by_pdb_adjacency": true, "candidate_roof_propyl_tail_mapping_supported_by_pdb_adjacency": true, "interpretation": "The numbered source schemes and serial-level PDB adjacency support a candidate map for the six-carbon B29 alkyne linker and the three-carbon macrocycle propyl-azide tail. Under this map, two propyl-tail carbons are in LYX and one is in MC; the source macrocycle formula therefore leaves 54 carbons expected in the MC residue, while both model files contain 56. The two-carbon inventory surplus is localized to the MC residue under this candidate partition, but the two unsupported/duplicated MC atom records are not identified.", "not_established": [ "a complete atom-mapped graph for either conjugate state", "which individual MC carbon records account for the two-carbon excess", "bond orders, formal charges, stereochemistry, or protonation", "parameter quality or force-field compatibility", "production-MD readiness" ], "target_binding_md_started": false, "clinical_use": false } }