{ "title": "Explicit phosphotyrosine changes modeled DOK7-CRKL contact geometry", "release_date": "2026-09-13", "evidence_type": "descriptive AlphaFold 3 sensitivity analysis", "constructs": { "DOK7": { "accession": "Q18PE1", "residues": "380-430", "chain": "A", "local_to_canonical": { "16": 395, "26": 405 } }, "CRKL": { "accession": "P46109", "residues": "1-120", "chain": "B" } }, "design": { "arms": [ "WT_UNMODIFIED", "PY395", "PY405", "DOUBLE_PY" ], "seeds_per_arm": [ 1, 2, 3 ], "samples_per_seed": [ 0, 1, 2, 3, 4 ], "models_per_arm": 15, "models_total": 60, "seeds_are_not_biological_replicates": true }, "contact_definition": { "distance_angstrom": 4.0, "boundary": "inclusive", "all_site_heavy_atoms": "All observed non-hydrogen atoms in the TYR or PTR site residue.", "common_TYR_PTR_scaffold": [ "C", "CA", "CB", "CD1", "CD2", "CE1", "CE2", "CG", "CZ", "N", "O", "OH" ], "PTR_only_phosphate_atoms": [ "P", "O1P", "O2P", "O3P" ], "reported_value": "Number of distinct CRKL construct positions within 4.0 Å in one model." }, "site_summary": [ { "arm": "WT_UNMODIFIED", "arm_label": "Unmodified", "site_local_position": 16, "site_canonical_position": 395, "site_component": "TYR", "models": 15, "all_partner_positions_min": 0, "all_partner_positions_median": 5, "all_partner_positions_max": 7, "all_models_with_contact": 14, "common_scaffold_partner_positions_min": 0, "common_scaffold_partner_positions_median": 5, "common_scaffold_partner_positions_max": 7, "common_scaffold_models_with_contact": 14, "phosphate_partner_positions_min": null, "phosphate_partner_positions_median": null, "phosphate_partner_positions_max": null, "phosphate_models_with_contact": null, "all_minus_common_models_nonzero": 0, "all_minus_common_sample_partner_events": 0, "all_minus_common_crkl_position_frequency": "", "phosphate_present": false }, { "arm": "WT_UNMODIFIED", "arm_label": "Unmodified", "site_local_position": 26, "site_canonical_position": 405, "site_component": "TYR", "models": 15, "all_partner_positions_min": 0, "all_partner_positions_median": 3, "all_partner_positions_max": 5, "all_models_with_contact": 14, "common_scaffold_partner_positions_min": 0, "common_scaffold_partner_positions_median": 3, "common_scaffold_partner_positions_max": 5, "common_scaffold_models_with_contact": 14, "phosphate_partner_positions_min": null, "phosphate_partner_positions_median": null, "phosphate_partner_positions_max": null, "phosphate_models_with_contact": null, "all_minus_common_models_nonzero": 0, "all_minus_common_sample_partner_events": 0, "all_minus_common_crkl_position_frequency": "", "phosphate_present": false }, { "arm": "PY395", "arm_label": "pY395", "site_local_position": 16, "site_canonical_position": 395, "site_component": "PTR", "models": 15, "all_partner_positions_min": 8, "all_partner_positions_median": 8, "all_partner_positions_max": 8, "all_models_with_contact": 15, "common_scaffold_partner_positions_min": 4, "common_scaffold_partner_positions_median": 6, "common_scaffold_partner_positions_max": 7, "common_scaffold_models_with_contact": 15, "phosphate_partner_positions_min": 4, "phosphate_partner_positions_median": 5, "phosphate_partner_positions_max": 5, "phosphate_models_with_contact": 15, "all_minus_common_models_nonzero": 15, "all_minus_common_sample_partner_events": 33, "all_minus_common_crkl_position_frequency": "21:15;39:3;42:10;43:5", "phosphate_present": true }, { "arm": "PY395", "arm_label": "pY395", "site_local_position": 26, "site_canonical_position": 405, "site_component": "TYR", "models": 15, "all_partner_positions_min": 0, "all_partner_positions_median": 1, "all_partner_positions_max": 6, "all_models_with_contact": 12, "common_scaffold_partner_positions_min": 0, "common_scaffold_partner_positions_median": 1, "common_scaffold_partner_positions_max": 6, "common_scaffold_models_with_contact": 12, "phosphate_partner_positions_min": null, "phosphate_partner_positions_median": null, "phosphate_partner_positions_max": null, "phosphate_models_with_contact": null, "all_minus_common_models_nonzero": 0, "all_minus_common_sample_partner_events": 0, "all_minus_common_crkl_position_frequency": "", "phosphate_present": false }, { "arm": "PY405", "arm_label": "pY405", "site_local_position": 16, "site_canonical_position": 395, "site_component": "TYR", "models": 15, "all_partner_positions_min": 0, "all_partner_positions_median": 0, "all_partner_positions_max": 1, "all_models_with_contact": 1, "common_scaffold_partner_positions_min": 0, "common_scaffold_partner_positions_median": 0, "common_scaffold_partner_positions_max": 1, "common_scaffold_models_with_contact": 1, "phosphate_partner_positions_min": null, "phosphate_partner_positions_median": null, "phosphate_partner_positions_max": null, "phosphate_models_with_contact": null, "all_minus_common_models_nonzero": 0, "all_minus_common_sample_partner_events": 0, "all_minus_common_crkl_position_frequency": "", "phosphate_present": false }, { "arm": "PY405", "arm_label": "pY405", "site_local_position": 26, "site_canonical_position": 405, "site_component": "PTR", "models": 15, "all_partner_positions_min": 8, "all_partner_positions_median": 8, "all_partner_positions_max": 9, "all_models_with_contact": 15, "common_scaffold_partner_positions_min": 5, "common_scaffold_partner_positions_median": 5, "common_scaffold_partner_positions_max": 8, "common_scaffold_models_with_contact": 15, "phosphate_partner_positions_min": 4, "phosphate_partner_positions_median": 5, "phosphate_partner_positions_max": 7, "phosphate_models_with_contact": 15, "all_minus_common_models_nonzero": 15, "all_minus_common_sample_partner_events": 38, "all_minus_common_crkl_position_frequency": "21:14;39:9;40:1;42:12;43:2", "phosphate_present": true }, { "arm": "DOUBLE_PY", "arm_label": "pY395 + pY405", "site_local_position": 16, "site_canonical_position": 395, "site_component": "PTR", "models": 15, "all_partner_positions_min": 2, "all_partner_positions_median": 4, "all_partner_positions_max": 7, "all_models_with_contact": 15, "common_scaffold_partner_positions_min": 1, "common_scaffold_partner_positions_median": 3, "common_scaffold_partner_positions_max": 6, "common_scaffold_models_with_contact": 15, "phosphate_partner_positions_min": 2, "phosphate_partner_positions_median": 3, "phosphate_partner_positions_max": 6, "phosphate_models_with_contact": 15, "all_minus_common_models_nonzero": 13, "all_minus_common_sample_partner_events": 21, "all_minus_common_crkl_position_frequency": "21:3;39:3;40:1;41:1;42:9;43:1;44:2;49:1", "phosphate_present": true }, { "arm": "DOUBLE_PY", "arm_label": "pY395 + pY405", "site_local_position": 26, "site_canonical_position": 405, "site_component": "PTR", "models": 15, "all_partner_positions_min": 6, "all_partner_positions_median": 8, "all_partner_positions_max": 10, "all_models_with_contact": 15, "common_scaffold_partner_positions_min": 4, "common_scaffold_partner_positions_median": 5, "common_scaffold_partner_positions_max": 6, "common_scaffold_models_with_contact": 15, "phosphate_partner_positions_min": 2, "phosphate_partner_positions_median": 5, "phosphate_partner_positions_max": 7, "phosphate_models_with_contact": 15, "all_minus_common_models_nonzero": 15, "all_minus_common_sample_partner_events": 40, "all_minus_common_crkl_position_frequency": "21:10;39:6;40:2;42:12;43:8;44:2", "phosphate_present": true } ], "interpretation_limits": [ "The four arms are separate model runs; matching seed and sample labels do not establish paired random draws.", "Contact geometry, pLDDT and PAE do not measure binding affinity, recruitment, activation, NMJ function or SMA efficacy.", "All-minus-common isolates contacts that appear only when additional PTR atoms are admitted within one model; it does not isolate every conformational or tokenization effect between arms.", "The earlier F/E/D substitution panel has different chemistry and denominators and is not pooled with this dataset." ] }