§12.4 pushed to its limit. Meeko ligand prep + in-place symmetry RMSD
(spyrmsd, not obrms) on clean HDAC2/vorinostat: 7.9A -> 4.76A. Prep and
metric mattered, but still FAIL.
Residual cause is fundamental: vorinostat binds via hydroxamate-Zn
chelation and Vina has no metal-coordination term. Real finding: sickle's
druggable targets bind via non-classical chemistry classical docking
handles poorly -- Hb (covalent), PKR (allosteric+cofactor), HDAC (Zn
chelation). Vina is the wrong tool for this target landscape.
Redirect: data-driven AF3-class co-folding (Boltz-2/Chai-1/DiffDock)
handles these modes -- the indicated next tool, gated by the 24GB local
memory ceiling (cloud GPU needed). The "GPU breaks all-local" §12.6
prediction is now the binding constraint of the track.
Adds: scripts/dock_production.py; deps meeko, spyrmsd, gemmi.
Co-Authored-By: Claude Opus 4.8 (1M context) <noreply@anthropic.com>
