5. BindCraft Project Setup

Looking for a step-by-step walkthrough?
Check out our in-depth BindCraft tutorial for miniprotein design or our peptide design guide for therapeutic peptide workflows.

This section guides you through configuring and launching a BindCraft design project for both miniprotein and peptide design workflows.

5.1 Choosing Your Project Type

BindCraft supports two design modalities, each optimized for different applications:

Miniprotein Projects

Size range: 31-150 amino acids (default: 65-150)
Applications: Stable protein binders, therapeutic biologics, research tools
Design protocols: 4-stage multimer workflows with various advanced options
Filters: Default, relaxed, or no filters

Peptide Projects

Size range: 8-30 amino acids (default: 8-25)
Applications: Small molecule-like binders, cell-penetrating agents, drug leads
Design protocols: 3-stage peptide-optimized workflows
Filters: Peptide-specific, peptide relaxed, or no filters

The interface will automatically configure appropriate settings based on your project type selection.

5.2 Uploading Your Target PDB

To begin, upload a PDB file of your target protein. For best results and faster processing, try to trim your structure to fewer than 300 amino acids. If your file is too large or incorrectly formatted, you'll see an error message with guidance on how to fix it.

Alternatively, you can search the RCSB database directly by PDB ID (e.g., "2B5I") or keyword (e.g., "IL-2RB") to automatically load structures.

5.3 Selecting Chains & Hotspots

After uploading, you'll see a list of protein chains found in your PDB. Select the chains you want BindCraft to target—any chains you leave unchecked will be ignored. If you want to focus the designs to bind specific regions of the target, you can optionally enter "hotspot" residues using chain letters and residue numbers (for example: A45 for a specific residue, B10-20 for a range of residues, or A for an entire chain).

5.4 BindCraft Design Settings

Binder Length Configuration

The length settings depend on your project type:

Miniprotein Projects:

Range: 31-150 amino acids (minimum enforced at 31)
Default: 65-150 amino acids
Note: Designs shorter than 31 amino acids will prompt you to switch to peptide mode

Peptide Projects:

Range: 8-30 amino acids (strictly enforced)
Default: 8-25 amino acids
Note: Designs longer than 30 amino acids are not permitted

Number of Designs

Choose how many designs to generate. The BindCraft authors recommend starting with 100 or more, then testing the top 5–20 ranked candidates.

Filter Settings

Filter options vary by project type:

Miniprotein Projects:

Default Filters: Standard acceptance criteria for miniproteins
Relaxed Filters: More permissive criteria (may increase experimental risk)
No Filters: Accept all designs (highest experimental risk)

Peptide Projects:

Peptide Filters: Optimized acceptance criteria for peptide binders
Peptide Relaxed Filters: More permissive peptide-specific criteria
No Filters: Accept all designs

Advanced Settings

Protocol options are tailored to each project type:

Miniprotein Projects:

Default 4-Stage Multimer: Standard protocol for miniprotein design
Beta-sheet variants: Promote beta sheet structures
Flexible options: Allow target flexibility (higher experimental risk)
Hard Target options: Use initial guess for difficult targets
MPNN variants: Use soluble MPNN for interface optimization

Peptide Projects:

Peptide 3-Stage Multimer: Standard protocol optimized for peptides
Flexible variant: Allow target flexibility during peptide design
MPNN variants: Use MPNN optimization for peptide interfaces

5.5 GPU Selection Preferences

Choose which GPUs are acceptable for your project. You can select multiple types. To prioritize cost savings, choose "Cost" mode; for speed and larger proteins, choose "Performance." Note: You must select at least one of H100, A100, or L40 due to availability.

5.6 Validating Settings & Starting BindCraft

When you're ready, click Validate Settings to check your setup for any issues. The validation will ensure:

Project type and length settings are compatible
Target structure is properly formatted
Chain selections are valid
GPU requirements are met

If everything looks good, you'll be able to start your design job by clicking Start BindCraft. You can monitor progress and see helpful messages in the Log Viewer. Once your project is submitted, you'll get an email and be redirected to your project's status page.

Next: 6. Project Detail Page for deeper insights into monitoring runs, viewing trajectories, and downloading results.