Validate drug target hypotheses using multi-dimensional computational evidence before committing to wet-lab work. Produces a quantitative Target Validation Score (0-100) with priority tier classification and GO/NO-GO recommendation.
Key Principles
Report-first
- Create report file FIRST, then populate progressively
Target disambiguation FIRST
- Resolve all identifiers before analysis
Evidence grading
- Grade all evidence as T1 (experimental) to T4 (computational)
Disease-specific
- Tailor analysis to disease context when provided
Modality-aware
- Consider small molecule vs biologics tractability
Safety-first
- Prominently flag safety concerns early
Quantitative scoring
- Every dimension scored numerically (0-100 composite)
Negative results documented
- "No data" is data; empty sections are failures
Source references
- Every statement must cite tool/database
English-first queries
- Always use English terms in tool calls; respond in user's language
When to Use
Apply when users ask about:
"Is [target] a good drug target for [disease]?"
Target validation, druggability assessment, or target prioritization
Leverage structural biology for druggability and mechanism understanding.
Key tools
:
UniProt_get_entry_by_accession
- Extract PDB cross-references
get_protein_metadata_by_pdb_id
/
pdbe_get_entry_summary
/
pdbe_get_entry_quality
alphafold_get_prediction
/
alphafold_get_summary
- pLDDT confidence
ProteinsPlus_predict_binding_sites
- Druggable pockets
InterPro_get_protein_domains
/
InterPro_get_domain_details
- Domain architecture
Phase 9: Literature Deep Dive
Comprehensive collision-aware literature analysis.
Steps
:
Collision detection
Search
"{gene_symbol}"[Title]
in PubMed; if >20% off-topic, add filters (AND protein OR gene OR receptor)
Publication metrics
Total count, 5-year trend, drug-focused subset
Key reviews
:
review[pt]
filter in PubMed
Citation metrics
:
openalex_search_works
for impact data
Broader coverage
:
EuropePMC_search_articles
Phase 10: Validation Roadmap (Synthesis)
Synthesize all phases into actionable output:
Target Validation Score
(0-100) with component breakdown
Priority Tier
(1-4) assignment
GO/NO-GO Recommendation
with justification
Recommended Validation Experiments
Tool Compounds for Testing
Biomarker Strategy
Key Risks and Mitigations
Report Output
Create file:
[TARGET]_[DISEASE]_validation_report.md
Use the full template from
REPORT_TEMPLATE.md
. Key sections:
Executive Summary (score, tier, recommendation, key findings, critical risks)
Validation Scorecard (all 12 sub-scores with evidence)
Sections 1-14 covering each phase
Completeness Checklist (mandatory before finalizing)
Complete the
Completeness Checklist
(in REPORT_TEMPLATE.md) before finalizing to verify all phases were covered, all scores justified, and negative results documented.