[cschanhniem]

Summary

Closes three synthesis risk detection gaps found in a best-practice audit of the presynth QC module:

1. QG/QS Glutamine deamidation hotspots (previously missed)

The existing regex only caught N[GS] (Asn deamidation). Glutamine (Q) undergoes the same succinimide-mediated deamidation → glutamate via Q[GS] motifs, documented by Geiger & Clarke (1987) J Biol Chem. Updated _DEAMIDATION_RE from N[GS] to [NQ][GS]. Affects variants with Q substitutions from SEED-001/003/006 families.

2. DG/DS Aspartate isomerization hotspots (new isomerization_sites field)

D[GS] motifs form β-aspartyl peptides via succinimide intermediate (Tyler-Cross & Schirch 1991). These rearrangements change backbone geometry and can eliminate antimicrobial activity. New isomerization_sites: list[str] field + ISOMERIZATION_RISK flag with HPLC verification guidance.

3. Trp photolability flag for SEED-008 family (new trp_photolability_risk field)

SEED-008 (puroindoline-a: FPVTWRWWKWWKG) and its variants carry 3–5 Trp residues. Trp photooxidizes to kynurenine under standard lab fluorescent lighting (Agon et al. 2006 Anal Biochem). Peptides with ≥3 Trp lose >20% activity within 4h under normal conditions. New trp_photolability_risk: bool field + TRP_PHOTOLABILITY flag with storage protocol: amber vials, dim light, 2h assay window.

Key design choice: Both TRP_PHOTOLABILITY and N_ACETYLATION_RECOMMENDED are appended after synthesis_difficulty is set — they are storage/guidance flags, not synthesis complexity flags.

WET_LAB_HANDOFF.md updated

New table rows for DEAMIDATION_RISK (expanded), ISOMERIZATION_RISK, and TRP_PHOTOLABILITY with specific lab action guidance.

Test plan

• 24 new tests (8 per category): TestDeamidationCompleteness, TestAspartateIsomerization, TestTrpPhotolability
• All 982 tests pass
• Verify: python -m pytest tests/test_presynth_qc.py -v