5. Miniprotein Design Setup

This section guides you through configuring and launching a miniprotein design project using our BindCraft workflow.

5.1 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.

5.2 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).

5.3 BindCraft Design Settings

• Binder Lengths: Set the minimum and maximum lengths for your miniproteins (default range is 65–150 amino acids).
• Number of Designs: Choose how many designs to generate. The BindCraft authors recommend starting with 100 or more, then testing the top 5–20.
• Filter Settings: Decide how strict you want the acceptance criteria to be. Relaxed filters will allow more designs through but may increase the risk of experimental failure. Peptide filters are optimized for peptide binders.
• Advanced Settings: Pick a specialized design protocol:
  • Beta-sheet: Promotes beta sheet structures
  • Peptide: Optimized for helical peptide binders
  • Flexible: Allows target flexibility (higher experimental risk)
  • HardTarget: Uses an initial guess for difficult targets
  • MPNN: Uses soluble MPNN for interface optimization

5.4 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.

5.5 Validating Settings & Starting BindCraft

When you’re ready, click Validate Settings to check your setup for any issues. 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.