protein-qclisted

# Protein Design Quality Control ## Critical Limitation **Individual metrics have weak predictive power for binding**. Research shows: - Individual metric ROC AUC: 0.64-0.66 (slightly better than random) - Metrics are **pre-screening filters**, not affinity predictors - **Composite scoring is essential** for meaningful ranking These thresholds filter out poor designs but do NOT predict binding affinity. ## QC Organization QC is organized by **purpose** and **level**: | Purpose | What it assesses | Key metrics | |---------|------------------|-------------| | **Binding** | Interface quality, binding geometry | ipTM, PAE, SC, dG, dSASA | | **Expression** | Manufacturability, solubility | Instability, GRAVY, pI, cysteines | | **Structural** | Fold confidence, consistency | pLDDT, pTM, scRMSD | Each category has two levels: - **Metric-level**: Calculated values with thresholds (pLDDT > 0.85) - **Design-level**: Pattern/motif detection (odd cysteines, NG sites) --- ## Quick Reference: All Thresholds | Category | Metric | Standard | Stringent | Source | |----------|--------|----------|-----------|--------| | **Structural** | pLDDT | > 0.85 | > 0.90 | AF2/Chai/Boltz | | | pTM | > 0.70 | > 0.80 | AF2/Chai/Boltz | | | scRMSD | < 2.0 Å | < 1.5 Å | Design vs pred | | **Binding** | ipTM | > 0.50 | > 0.60 | AF2/Chai/Boltz | | | PAE_interaction | < 12 Å | < 10 Å | AF2/Chai/Boltz | | | Shape Comp (SC) | > 0.50 | > 0.60 | PyRosetta | | | interface_dG | < -10 | < -15 | PyRosetta | |