PROTAC Builder

A next-generation platform for rapid degrader design — bridging chemistry, structural biology, and AI-assisted modeling.

PROTAC Builder Cheats & Notes

Quick Start

Build a PROTAC from three modular pieces

PROTAC Builder helps you assemble a degrader by combining a warhead / target ligand, a linker, and an E3 ligase recruiter.

Warhead

Select from V-LiSEMOD, paste a SMILES, or draw/edit your own target-binding ligand.

Linker

Choose a curated linker, filter by properties, paste a SMILES, or design one manually.

Ligase

Select or load an E3 ligase recruiter, then define where the linker should attach.

Attachment Atom Cheat Sheet

Mark the connection points before saving

Warhead: add a bonded U atom at the warhead attachment site.
Linker: add U at the warhead-facing end and V at the ligase-facing end.
Ligase recruiter: add a bonded V atom at the ligase recruiter attachment site.

After editing each panel, click Save under Warhead, Linker, and Ligase Recruiter. Then click Generate PROTAC.

Loading Molecules

Use SMILES when you already know the structure

Click Load from SMILES under the Warhead, Linker, or Ligase Recruiter panel, paste a valid SMILES string, and load it into the editor.

Once loaded, you can modify the molecule, add the required U/V attachment atom, and click Save.

Companion Tools

Use the discovery tools when you need help choosing components

Warhead Hunter: helps identify or import target-binding warheads.
E3 Ligandalyzer: helps explore E3 ligase recruiter options.
V-LiSEMOD: provides selectable warheads from the builder dropdown.

Shareable Builder Links

Open PROTAC Builder with molecules already loaded

Advanced users can create links that preload a warhead, linker, or ligase recruiter.

Builder https://protacbuilder.com/builder

Warhead SMILES https://protacbuilder.com/builder?smiles=ENCODED_WARHEAD_SMILES

Linker SMILES https://protacbuilder.com/builder?linker=ENCODED_LINKER_SMILES

Ligase Recruiter https://protacbuilder.com/builder?ligase=LIGASE_NAME

Multiple Pieces https://protacbuilder.com/builder?smiles=WARHEAD_SMILES&linker=LINKER_SMILES&ligase=LIGASE_NAME

Developer Notes

Local testing and query parameter reference

Local development builder URL: http://192.168.1.154:5069/builder

Supported warhead preload parameters:

?smiles= ?lig_smi= ?warhead_smiles= ?warheadSmiles=

Backend/database ligand preload: /builder?ligand=YOUR_LIGAND_CODE

Real SMILES should be URL-encoded before being placed into a link: encodeURIComponent(smiles)

const url =
  "/builder?smiles=" +
  encodeURIComponent(warheadSmiles) +
  "&linker=" +
  encodeURIComponent(linkerSmiles) +
  "&ligase=" +
  encodeURIComponent(ligaseName);

Select Warhead From V-LiSEMOD:

Select Linker:

Select Ligase: 🔍

Modify Warhead ⓘ

Modify Linker ⓘ

Selected Ligase ⓘ

🏠

Choose how you want to start:

Open E3 Ligandalyzer

PROTAC Builder

Modify Warhead ⓘ

Modify Linker ⓘ

Selected Ligase ⓘ

Generated PROTAC