tpd-ternary-complex-agent — independently scanned and version-tracked by SaferSkills.
SaferSkills independently audited tpd-ternary-complex-agent (Agent Skill) and scored it 100/100 (green). The audit ran 55 deterministic rules across Security, Supply Chain, Maintenance, Transparency, and Community; it found 0 high-severity and 0 lower-severity findings. The full rule-by-rule trace and per-finding evidence are below. Free, methodology-open.
Findings & checks · 0 flagged
Every scanned point with the score it earned and what moved between them.
First recorded scan — no prior version to compare against.
The primary manifest — the file an agent reads to learn what this artifact does.
The TPD Ternary Complex Agent specializes in predicting and modeling ternary complex formation for targeted protein degradation (TPD). It uses AlphaFold-Multimer, molecular dynamics, and deep learning to model Protein of Interest (POI)-degrader-E3 ligase assemblies, enabling rational optimization of PROTACs and molecular glues.
| E3 Ligase | Structure | Complex Quality |
|---|---|---|
| CRBN-DDB1-CUL4A | High resolution | Excellent |
| VHL-ELOB-ELOC-CUL2 | High resolution | Excellent |
| MDM2 | Good | Good |
| IAP (cIAP1/XIAP) | Moderate | Moderate |
| DCAF15-DDB1 | Emerging | Developing |
| KEAP1 | High resolution | Good |
User: "Model the ternary complex for this BRD4 PROTAC with VHL to understand the protein-protein interface."
Agent Action:
python3 Skills/Drug_Discovery/TPD_Ternary_Complex_Agent/predict_ternary.py \
--poi_structure brd4_bd1.pdb \
--warhead_pose brd4_warhead_docked.sdf \
--e3_ligase VHL \
--e3_ligand vhl_ligand.sdf \
--protac_smiles "PROTAC_SMILES_STRING" \
--linker_conformations 100 \
--md_refinement true \
--output ternary_complex_results/| Score Component | Weight | Interpretation |
|---|---|---|
| Interface Area | 20% | Larger = more stable |
| Shape Complementarity | 25% | Better fit = stability |
| Electrostatics | 20% | Charge matching |
| Linker Strain | 15% | Lower = better geometry |
| Complex Stability (ΔG) | 20% | Favorable energetics |
| Output | Description | Format |
|---|---|---|
| Ternary Structure | POI-PROTAC-E3 model | .pdb |
| Confidence Scores | pLDDT, PAE | .json |
| Interface Map | Contact residues | .csv |
| Lysine Accessibility | Ubiquitination sites | .csv |
| Cooperativity | α factor estimate | .json |
| Optimization Suggestions | Design recommendations | .md |
| MD Trajectory | Stability simulation | .xtc |
| Metric | Definition | Good Value |
|---|---|---|
| Buried Surface Area | Contact area | >800 Ų |
| Shape Complementarity | Sc score | >0.65 |
| Gap Volume Index | Interface packing | <2.0 |
| Hydrogen Bonds | Intermolecular H-bonds | >3 |
| Salt Bridges | Charged interactions | >1 |
Structure Prediction:
Conformational Sampling:
Scoring Functions:
| α Factor | Interpretation | Mechanism |
|---|---|---|
| α > 1 | Positive cooperativity | E3 binding enhances POI binding |
| α = 1 | No cooperativity | Independent binding |
| α < 1 | Negative cooperativity | E3 binding reduces POI binding |
| Requirement | Threshold | Rationale |
|---|---|---|
| Surface Accessibility | >30 Ų | E2 access |
| Distance to E2~Ub | <15 Å | Transfer distance |
| Lysine Environment | Favorable | Not buried |
| Number of Sites | ≥1 | At least one Lys |
| E3 | Advantages | Considerations |
|---|---|---|
| CRBN | Broad applicability, many ligands | Some immune targets |
| VHL | High selectivity, well-validated | Limited tissue in some organs |
| MDM2 | No CRBN competition | Fewer validated targets |
| IAP | Cancer expression, dual mechanism | Complex biology |
| Method | Purpose | Confidence |
|---|---|---|
| Crystal Structure | Ground truth | Highest |
| Cryo-EM | Large complexes | High |
| HDX-MS | Interface mapping | Moderate-High |
| Crosslinking MS | Distance constraints | Moderate |
| Mutagenesis | Interface validation | Functional |
| Structural Finding | Design Action |
|---|---|
| Poor interface | Change E3 or target site |
| Long distance | Longer linker |
| Steric clash | Shorter linker or different exit vector |
| No accessible Lys | Different binding mode |
| High flexibility | Constrained linker |
| QC Metric | Threshold | Interpretation |
|---|---|---|
| pLDDT (interface) | >70 | Reliable prediction |
| PAE (POI-E3) | <10 Å | Good relative positioning |
| MD RMSD | <3 Å | Stable complex |
| Clash Score | <50 | Good packing |
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