PROTAC inputs and parameters
Warhead SMILES, E3 ligand structures, linker constraints, and scoring options for all PROTAC design tools.
protacinputs
You provide warhead and E3 ligand SMILES, a full PROTAC structure, and POI/E3 structures; the choice of E3 system and linker length and flexibility constraints most shape which candidate degraders you get back.
PROTAC inputs and parameters
Common input formats
Most PROTAC tools accept one or more of these input types:
| Input | Format | Example | Accepted By |
|---|---|---|---|
| Warhead SMILES | Valid SMILES string | CC1=CC(=O)N(C2=CC=CC=C2)C1=O | Linker Enumerate |
| E3 ligand SMILES | Valid SMILES string | O=C1CCC(N2CC3=CC=CC=C3C2=O)C(=O)N1 | Linker Enumerate |
| Full PROTAC SMILES | Valid SMILES string | Warhead-linker-E3 ligand | Ternary Model, Degradation Score |
| POI structure | PDB ID or uploaded file | 3MXF | Ternary Model |
| E3 structure | PDB ID or uploaded file | 4CI1 (CRBN), 4W9H (VHL) | Ternary Model |
| E3 system | Enum string | CRBN, VHL | All tools |
| Job ID | UUID from previous run | job_abc123 | Degradation Score (ternary input) |
PROTAC Linker Enumerate parameters
| Parameter | Type | Required | Default | Description |
|---|---|---|---|---|
warhead_smiles | string | Yes | -- | SMILES of the POI-binding warhead |
e3_ligand_smiles | string | Yes | -- | SMILES of the E3 ligase recruiting ligand |
e3_system | string | No | "CRBN" | E3 ligase system: "CRBN" or "VHL" |
min_linker_length | integer | No | 4 | Minimum linker length in atoms (shortest path) |
max_linker_length | integer | No | 12 | Maximum linker length in atoms (shortest path) |
scaffold_type | string | No | "diverse" | Linker scaffold chemistry |
num_linkers | integer | No | 50 | Number of linkers to generate (1-200) |
max_rotatable_bonds | integer | No | 10 | Maximum rotatable bonds in the linker |
sa_threshold | number | No | 5.0 | Maximum synthetic accessibility score (1-10, lower = easier) |
Scaffold types
| Value | Chemistry | Description |
|---|---|---|
"diverse" | Mixed | Balanced mix of all scaffold types |
"peg" | PEG | Polyethylene glycol chains (hydrophilic, flexible) |
"alkyl" | Alkyl | Carbon chains (hydrophobic, flexible) |
"piperazine" | Piperazine | Piperazine-containing (rigid, basic nitrogen) |
"triazole" | Triazole | Click-chemistry-compatible (rigid, metabolically stable) |
"hybrid" | Mixed rigid/flexible | Combines rigid and flexible elements |
Linker length guidelines
| Length (atoms) | Typical Use |
|---|---|
| 4-6 | Short linkers, tight ternary complexes |
| 6-10 | Most common range, balanced flexibility |
| 10-14 | Long linkers, accommodates distant binding sites |
| > 14 | Very long, often poor drug-likeness |
PROTAC Ternary Model parameters
| Parameter | Type | Required | Default | Description |
|---|---|---|---|---|
protac_smiles | string | Yes | -- | SMILES of the full PROTAC molecule |
poi_structure | string | Yes | -- | PDB ID or uploaded structure file for the protein of interest |
e3_structure | string | No | Auto-selected | PDB ID or uploaded structure file for the E3 ligase |
e3_system | string | No | "CRBN" | E3 ligase system: "CRBN" or "VHL" |
poi_binding_site | string | No | Auto-detected | Residue range for POI binding site (e.g., "A:100-120") |
num_conformers | integer | No | 10 | Number of ternary complex conformers to sample (1-50) |
clash_tolerance | number | No | 2.0 | Steric clash tolerance in Angstroms |
Common E3 ligase structures
| E3 System | PDB ID | Description |
|---|---|---|
| CRBN | 4CI1 | CRBN-DDB1 with pomalidomide |
| CRBN | 5FQD | CRBN-DDB1 with lenalidomide |
| VHL | 4W9H | VHL-ElonginB-ElonginC with VH032 |
| VHL | 5NVX | VHL-ElonginB-ElonginC with MZ1 |
PROTAC Degradation Score parameters
| Parameter | Type | Required | Default | Description |
|---|---|---|---|---|
protac_smiles | string | Yes | -- | SMILES of the full PROTAC molecule |
e3_system | string | No | "CRBN" | E3 ligase system: "CRBN" or "VHL" |
ternary_job_id | string | No | -- | Job ID from a previous ternary model run (improves accuracy) |
poi_name | string | No | -- | Target protein name for context (e.g., "BRD4") |
cell_type | string | No | "general" | Cell type context for expression-adjusted scoring |
Cell type options
| Value | Description |
|---|---|
"general" | Expression-agnostic scoring |
"hek293" | HEK293 cell expression levels |
"hela" | HeLa cell expression levels |
"jurkat" | Jurkat T-cell expression levels |
"mcf7" | MCF-7 breast cancer cell expression levels |
SMILES format requirements
Warhead and E3 ligand SMILES
- Must be valid, sanitizable SMILES strings
- Should contain explicit attachment points where the linker connects (marked with
[*]or left as open valences) - Stereochemistry should be specified where relevant (e.g., VHL ligands require correct hydroxyproline stereochemistry)
- Maximum 200 heavy atoms per fragment
Full PROTAC SMILES
- Must contain both the warhead and E3 ligand fragments connected by a linker
- Maximum 500 heavy atoms total
- Stereochemistry should be specified for E3 ligand and warhead stereocenters
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