PROTAC Builder — Digital Designer (Public Showcase)

A visual workspace for building proteolysis-targeting chimeras (PROTACs): select a warhead, filter from a library of experimentally reported linkers (via PROTAC-DB), choose a ligase recruiter, and export design files for downstream modeling and analysis.

▶ Watch the Tutorial · Open via V-LiSEMOD · Contact

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Table of Contents

• What It Does
• Quickstart
• Design Flow
• Linker Library & Filters
• Ligase Recruiters
• Outputs & Interop
• Screenshots
• Data Source & References
• Roadmap
• Privacy & Scope
• Credits
• License
• Contact

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What It Does

• Mix & match PROTAC components in a clean 3-pane editor (Warhead • Linker • Ligase).
• Start from real chemistry: browse >1,500 literature-reported linkers aggregated by PROTAC-DB (ZJU).
• Filter intelligently by molecular weight, flexibility/rigidity, polarity, xLogP, ring count, and more.
• Color-coded ligase recruiters and a Ligandalyzer view for quick comparison.
• Generate a candidate PROTAC and export files for docking/MD/analytics pipelines.

The builder is reachable from the V-LiSEMOD UI but is a separate tool. Source code is private; this repo is a docs-only showcase.

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Quickstart

1. Open V-LiSEMOD → choose PROTAC Builder (top nav).
2. Choose a Warhead
   • Import a SMILES/SDF, or pull a viral warhead you explored in V-LiSEMOD.
3. Pick a Linker via the Filter dialog.
4. Select a Ligase Recruiter (e.g., CRBN, VHL, MDM2, …).
5. Click Generate PROTAC → review the structure, download SMILES, or export files for analysis.

🎥 Full walkthrough: https://youtu.be/CYYsG1MpsE4

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Design Flow

1) Warhead (target-binding moiety)

• Draw or paste SMILES, or load from prior work (e.g., viral co-crystal analysis).
• Edit with ChemDoodle tools (R-group handles, atom edits, etc.).

2) Linker (experimentally grounded)

• Open the Select a Linker dialog to browse and filter (see below).
• Preview candidate linkers; select one to drop into the builder.

3) Ligase Recruiter (E3 binder)

• Choose a recruiter scaffold from the built-in library.
• Color-coded cards make families easy to scan.
• Open details to see an example co-crystal context and generate an interaction diagram.

4) Generate & Inspect

• Produce the full PROTAC structure.
• View generated SMILES and proceed to parameterization/exports.

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Linker Library & Filters

Library entries are curated from PROTAC-DB (published PROTACs). Filter by:

• MW (min/max)
• Flexibility / Rigidity
• Polarity
• xLogP
• Ring count

This narrows to linkers with the physicochemical profile you want before assembly.

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Ligase Recruiters

Includes common recruiters (examples shown):

• CRBN family (e.g., lenalidomide/pomalidomide derivatives)
• VHL binders
• MDM2 series

Browse with the Ligandalyzer grid, open details, and (where available) view 2D/3D context of a representative co-crystal.

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Outputs & Interop

After Generate PROTAC:

• SMILES string (copy or download)
• Design bundle suitable for downstream workflows (e.g., docking/MD prep)
• Optional routes to evaluate or prep in:
  • PRosettaC-style docking pipelines
  • JARI (internal linker analysis and design scoring)
  • Deep PK–style profiling (internal)

These integrations are optional and may require private tooling or separate access.

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Screenshots

• assets/protac-builder-3panels.png — Main 3-pane editor
• assets/ligandalyzer-grid.png — Ligase recruiter grid
• assets/ligase-details.png — Recruiter details with 3D view
• assets/ligandalyzer-grid-mdm2-vhl.png — Additional recruiter families
• assets/linker-filter.png — Linker filter dialog
• assets/protac-compose.png — Component selection complete
• assets/protac-generated.png — Final PROTAC + SMILES & exports

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Data Source & References

• Linker library: PROTAC-DB — curated database of published PROTACs and linkers
  https://cadd.zju.edu.cn/protacdb/
• Upstream context: V-LiSEMOD (viral warheads, pocket context, SASA, contacts)
  https://vlisemod.com

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Roadmap

• More recruiter families & metadata
• Linker similarity search and “design your own” templates
• One-click export packs for PRosettaC/JARI
• Session share links and audit trail

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Privacy & Scope

• This is an R&D and education tool; it does not provide clinical or regulatory guidance.
• The production app and code are private; this repository is documentation only.
• No patient/PHI data is processed.

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Credits

• Lead: Joseph-Michael Schulz
• Thanks to the PROTAC-DB team and the broader degraders community.

License

Documentation in this repository is released under the MIT License.
Application source code and proprietary datasets are private.

Contact

Access requests or collaborations: jmschulz@med.miami.edu

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Tutorial: https://youtu.be/CYYsG1MpsE4
Launch (via V-LiSEMOD): https://vlisemod.com