Corrected pipeline ran clean: 1 MSA query, 299/299 screened, 0 failures,
~$5-8 (vs the fragile 2.5hr/$15 version).
Results:
- Scale validation: HDAC inhibitors rank 1-9 (>=0.99); valproic-acid 0.90.
- DECISIVE specificity: best negative control = cetirizine rank 44 (P=0.39);
all 26 negative controls rank low. Co-folding REJECTS unrelated drugs --
exactly what connectivity could not do (where norethindrone/ciprofloxacin
ranked top). The modality-pivot thesis vindicated at screen scale.
- Discovery: BG-1003 (rank 5, P=0.997, random sample) is the standout
non-obvious binder, above several known HDAC inhibitors; also JW55,
BRD-K14666757. 11 drugs P>0.9 (8 known inhibitors + 3 non-obvious).
Caveats kept honest: BG-1003 may be a known HDAC inhibitor in the random
sample (validation, not novelty) -- needs identity check; binding != efficacy;
prodrug/macrocycle false negatives. Full ranking in docs/results/.
Co-Authored-By: Claude Opus 4.8 (1M context) <noreply@anthropic.com>
Junior B.
71069d3f10