---
title: PROTAC design quickstart
description: >-
  Step-by-step workflows for linker enumeration, ternary complex modeling, and
  degradation scoring.
tags:
  - protac
  - quickstart
---

You want to design a bifunctional degrader; these workflows take you from a warhead and E3 ligand through a linker library, ternary complex model, and degradation score. See [PROTAC design on the platform](/docs/protac) for tool details.

## PROTAC design quickstart

This guide covers three core workflows: enumerating linker libraries, modeling ternary complexes, and scoring degradation efficiency.

## Workflow 1: Enumerate PROTAC linkers

### Step 1: Provide warhead and E3 ligand SMILES

Ask Ivy in chat (or submit the job directly with `POST /api/v1/jobs`; see the [API reference](/docs/api)):

```
Enumerate PEG linkers connecting this warhead to a CRBN ligand:
Warhead: CC1=CC(=O)N(C2=CC=CC=C2)C1=O
E3 ligand: O=C1CCC(N2CC3=CC=CC=C3C2=O)C(=O)N1
```

Ivy runs PROTAC linker enumeration to generate a diverse linker library.

### Step 2: Review the linker library

| Field | Example Value |
|-------|---------------|
| Total linkers | 50 |
| Linker length range | 4-12 atoms |
| Scaffold types | PEG, alkyl, piperazine |
| Avg synthetic accessibility | 3.2 |
| Avg drug-likeness (QED) | 0.35 |

### Step 3: Filter by properties (optional)

```
Filter the linkers to only PEG scaffolds between 6 and 8 atoms with SA score below 4
```

This narrows the library to the most synthetically accessible candidates in the desired length range.

## Workflow 2: Model a ternary complex

### Step 1: Provide inputs

```
Model the ternary complex for this PROTAC with BRD4 and CRBN
PROTAC SMILES: [full PROTAC SMILES here]
POI PDB: 3MXF
E3 PDB: 4CI1
```

Or configure manually:

| Parameter | Value |
|-----------|-------|
| PROTAC SMILES | Full bifunctional molecule |
| POI structure | PDB ID or uploaded file |
| E3 ligase structure | PDB ID or uploaded file |
| E3 system | `CRBN` |

### Step 2: Review the ternary complex

| Field | Example Value |
|-------|---------------|
| Buried surface area | 1,850 A^2 |
| Shape complementarity | 0.72 |
| Clash count | 3 |
| Interface residues (POI) | 14 |
| Interface residues (E3) | 11 |
| Feasibility score | 0.81 |

### Step 3: Visualize the complex

The result includes a PDB file of the modeled ternary complex. View it in the Mol* 3D viewer on the canvas card to inspect the protein-protein interface and linker conformation.

## Workflow 3: Score degradation efficiency

### Step 1: Submit for scoring

```
Score this PROTAC for degradation efficiency:
SMILES: [full PROTAC SMILES here]
```

Or configure:

| Parameter | Value |
|-----------|-------|
| PROTAC SMILES | Full bifunctional molecule |
| E3 system | `CRBN` or `VHL` |
| Ternary complex job ID | (optional, from Workflow 2) |

### Step 2: Review degradation predictions

| Metric | Predicted Value | Interpretation |
|--------|----------------|----------------|
| DC50 | 18 nM | Potent degrader |
| Dmax | 92% | Near-complete degradation |
| Hook effect risk | Low | No dose-response inversion expected |
| Cooperativity (alpha) | 3.2 | Positive cooperativity in ternary complex |

### Step 3: Interpret the results

| DC50 Range | Interpretation |
|------------|----------------|
| < 10 nM | Highly potent degrader |
| 10 - 100 nM | Potent degrader |
| 100 nM - 1 uM | Moderate degrader |
| > 1 uM | Weak degrader |

| Dmax Range | Interpretation |
|------------|----------------|
| > 90% | Near-complete degradation |
| 70 - 90% | Good degradation |
| 50 - 70% | Partial degradation |
| < 50% | Insufficient degradation |

## Workflow 4: End-to-end PROTAC design

### Step 1: Start with a target

```
Design a PROTAC to degrade BRD4 using a CRBN-based E3 recruiter.
Use the JQ1 warhead and pomalidomide as the E3 ligand.
Enumerate 30 linkers between 4 and 10 atoms.
```

### Step 2: Model top candidates

```
Model ternary complexes for the top 5 linkers by drug-likeness score
```

### Step 3: Score degradation

```
Score degradation efficiency for all 5 ternary complex models
```

### Step 4: Select leads

Ivy will rank candidates by DC50, Dmax, and synthetic accessibility, recommending the most promising leads for synthesis.

## Next steps

- See [inputs](/docs/protac/inputs) for all parameters, SMILES formats, and constraint options
- See [outputs](/docs/protac/outputs) for result field descriptions and score interpretation
- Use [ADMET-AI](/docs/admet-ai) for drug-likeness profiling of PROTAC candidates
- Use [AiZynthFinder](/docs/aizynthfinder) for synthetic route planning

## Read next