{"compile":"2026-10-10","canonical":"https://aaronspradlin.grok.me/wiki/mecp2-rett","json":"https://aaronspradlin.grok.me/page.json?slug=mecp2-rett","license":"Source-available for noncommercial research and evaluation only. No commercial, product, platform, or service use without written permission.","scientific_breakthrough":false,"slug":"mecp2-rett","title":"MECP2 Rett MBD–DNA campaign","dek":"Aug 2025 Labs/MECP2. 16 Sep 2026 README: further testing did not support the findings; lab materials withdrawn. Do not rely on them as validation. Restricted/Corrected.","updated":"2026-09-19","status":"applied","claim":"corrected","tags":["protein","MECP2","Rett","R106W","R133C"],"related":["protein-audit","p53-campaign","protein-bridge-v9","applied-stack","claim-ledger","for-researchers","open-science"],"packages":[{"id":"labs-mecp2","name":"Labs/MECP2","path":"Labs/MECP2","status":"restricted"},{"id":"wetlab-root","name":"WetLabEngine (root)","path":"/","status":"supported"}],"notes":[],"claims":[{"status":"restricted","text":"Inside this 19-run coarse-grained campaign, InterfaceAnneal seated R106W and R133C MBD–DNA complexes to near-native RMSD, and post-anneal challenges held. The WT–DNA complex is a stable positive control. This is not a Rett therapy, not all-atom MD, and not a folding oracle."},{"status":"restricted","text":"Run 5 is a recorded DEVIATION: the unrescued-mutant contract (RMSD ≥ 20 Å) did not match the definitive 3.06 Å tail. Runs 1–3 are INDETERMINATE for missing diagnostics CSV. Cite the mismatch; do not drop it."}],"text":"Labs/MECP2 is a 19-run campaign on the methyl-CpG-binding domain of MeCP2, dated 26–28 Aug 2025. The contract is findings.json v3.3. The human abstract (abstract.txt) is titled Computational Audit and Verification of a Rescue Strategy for Rett Syndrome-Associated MECP2 Mutations and is attributed to “The Gemini Auditing Group.” There is no load-bearing X field note for this campaign in the current compile. Cite GitHub.\n\nThe engine’s own abstract reports 15 CONFIRMED, 1 DEVIATION, 3 INDETERMINATE. Isolated-MBD baselines (Runs 1–3) are INDETERMINATE because diagnostics_timeseries.csv is missing. Run 5 (unrescued R106W–DNA) was contracted as unstable (RMSD ≥ 20 Å) and the definitive tail median came back 3.06 Å — DEVIATION, not a quiet pass. Do not cite this campaign as 19/19 clean. This compile independently reproduced those three counts from the bound CSVs on 7 Sep 2026. Start there: Run this first on the WetLabEngine protein audit page.\n\nThesis in the contract\n\nMECP2 MBD Rett mutations destabilize DNA binding but can be rescued by stabilizing the encounter complex; WT complex is inherently stable.\n\nMachine test: count_runs_meeting where best_final_RMSD_A ≤ 4.5 must be ≥ 3. The audit abstract says 16 runs met that cutoff, so the thesis constraint passed. Passing a count constraint is not a therapeutic claim.\n\nCampaign map\n\nWhat a researcher should not write\n\nDo not write “MECP2 folding is solved.” Full-length WT is treated as IDP-like; the campaign is about the MBD–DNA interface.\nDo not write “R106W is unstable because RMSD is high.” Run 5 is the counterexample: a low RMSD that failed the instability claim.\nDo not write “interface annealing is a Rett therapy.” It is an in-silico protocol that seated mutant complexes in this coarse-grained model.\nDo not promote the thesis implications (ligand-design avenues, generalizable rescue) to Supported. They are manuscript discussion, Restricted at most.\n\nInside this 19-run coarse-grained campaign, InterfaceAnneal seated R106W and R133C MBD–DNA complexes to near-native RMSD, and post-anneal challenges held. The WT–DNA complex is a stable positive control. This is not a Rett therapy, not all-atom MD, and not a folding oracle.\n\nRun 5 is a recorded DEVIATION: the unrescued-mutant contract (RMSD ≥ 20 Å) did not match the definitive 3.06 Å tail. Runs 1–3 are INDETERMINATE for missing diagnostics CSV. Cite the mismatch; do not drop it.\n\nLabs/MECP2 on GitHub\nfindings.json v3.3\nRun this first (deterministic smoke)\nAuditor script\np53 campaign","howToCite":"Spradlin, A. (2026-10-10). MECP2 Rett MBD–DNA campaign. Retained Atlas. https://aaronspradlin.grok.me/wiki/mecp2-rett. Keep claim badge: corrected."}