§12.3-12.4 first binding result on ARM Mac.
- Toolchain SOLVED: AutoDock Vina 1.2.5 mac binary (Rosetta) + open-babel
(brew). No conda, no MLX. dock_positive_controls.py runs end-to-end.
- Cross-dock known binders + negatives into Hb (5E83) and PKR (8XFD),
box centered on co-crystal ligands (5L7=voxelotor, WV2=mitapivat).
Finding: raw Vina affinity ranks almost perfectly by MOLECULAR SIZE
(mitapivat > voxelotor > decitabine/caffeine > hydroxyurea) in both
pockets — mitapivat wins even on hemoglobin it doesn't target. Raw score
can't distinguish target-specific binding: the docking analog of the
connectivity specificity problem. Next: redocking-RMSD validation +
ligand-efficiency normalization.
Note: machine is 24GB (not 96GB per PLAN §2), capping local AF3-class
inference. tools/ gitignored (vina binary).
Co-Authored-By: Claude Opus 4.8 (1M context) <noreply@anthropic.com>
Junior B.
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