StruSel

Structurome-wide Selectivity of pathogen-exclusive targets

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Overview

StruSel is a computational pipeline for identifying pathogen-exclusive drug target candidates through proteome-scale structural comparison. It goes beyond traditional sequence-based homology exclusion by leveraging AI-predicted 3D structures to uncover proteins that are structurally divergent from the human proteome — representing a largely unexplored space for selective antimicrobial drug discovery.

Given a target pathogen, StruSel:

1. Downloads AlphaFold2-predicted structures for the pathogen proteome
2. Performs structurome-wide structural similarity search against the human structurome using FoldSeek (3Di-based)
3. Performs parallel sequence-based search using BLASTp for benchmarking
4. Identifies proteins uniquely classified as non-homologous by structural (but not sequence) analysis
5. Cross-references with essential gene databases to filter for essential proteins
6. Maps candidates to CARD to assess AMR relevance
7. Outputs a ranked, annotated list of pathogen-exclusive target candidates

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Use Case

Current implementation: Klebsiella pneumoniae (WHO critical priority pathogen)

Planned extension: Pan-ESKAPE (E. faecium, S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa, Enterobacter spp.)

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Pipeline Overview

Pathogen proteome (AlphaFold DB)
        │
        ▼
FoldSeek structural search ──────────────────┐
        │                                    │
BLASTp sequence search                       │
        │                                    │
        ▼                                    ▼
Structure-sequence decoupling          Non-homologs (structural)
        │
        ▼
Essential gene filtering (DEG / OGEE)
        │
        ▼
AMR mapping (CARD)
        │
        ▼
StruSel target candidates

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Repository Structure

strusel/
├── README.md
├── notebooks/
│   └── strusel_pipeline.ipynb    # Main Colab notebook
├── data/
│   └── .gitkeep                  # Input data (not tracked)
├── results/
│   └── .gitkeep                  # Output files (not tracked)
└── scripts/
    └── .gitkeep                  # Modular scripts (coming soon)

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Quick Start (Google Colab)

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Dependencies

• Python 3.8+
• FoldSeek
• BLAST+
• Biopython
• pandas, numpy
• requests (AlphaFold DB API)

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Citation

If you use StruSel, please cite:

Pranavathiyani G. StruSel: Structurome-wide Selectivity of pathogen-exclusive targets. GitHub. https://github.com/pranavathiyani/strusel

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Author

Pranavathiyani G
Assistant Professor (Research), Division of Bioinformatics
SASTRA Deemed University, Thanjavur
pranavathiyani@scbt.sastra.edu
Google Scholar | ORCID

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License

MIT License. See LICENSE for details.

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