> ## Documentation Index
> Fetch the complete documentation index at: https://docs.boltz.bio/llms.txt
> Use this file to discover all available pages before exploring further.

# Creating Binder Specifications

> Define protein binder specifications and design motifs

## Overview

Binder specifications define the protein binder properties (modality, structure, design regions) that will be used to generate candidates.

## Creating a New Binder Specification

<Frame>
  <img src="https://mintcdn.com/boltzpbc/kY8bkQpkfe_a5_5T/images/user-guide/protein-design/binder-1.png?fit=max&auto=format&n=kY8bkQpkfe_a5_5T&q=85&s=38dd150ea4426d79391d2b24cdbfaf76" alt="Nanobody specification structure selection" width="3000" height="948" data-path="images/user-guide/protein-design/binder-1.png" />
</Frame>

1. From your project dashboard, click **"+ Add"** in the Binder Specifications section.

2. **Step 1: Setup** - Give your binder specification a name and choose the protein modality:

   <CardGroup cols={4}>
     <Card title="Peptide">
       Design short peptide sequences
     </Card>

     <Card title="Antibody">
       Create antibody heavy and light chains
     </Card>

     <Card title="Nanobody">
       Design single-domain antibodies
     </Card>

     <Card title="Other">
       Other protein types
     </Card>
   </CardGroup>

3. Click **"> Continue to Specification"**.

## Starting Specification

### Option 1: Structure-Based Specification

<Frame>
  <img src="https://mintcdn.com/boltzpbc/kY8bkQpkfe_a5_5T/images/user-guide/protein-design/binder-2.png?fit=max&auto=format&n=kY8bkQpkfe_a5_5T&q=85&s=ab715c621c90b8074ebbcf180d6c900f" alt="Nanobody specification structure selection" width="2994" height="1696" data-path="images/user-guide/protein-design/binder-2.png" />
</Frame>

**Select a template:**

* Choose from pre-loaded structures (e.g., vWF A1-Caplacizumab Complex, IL-6R-Vobarilizumab Complex)
* Each template shows PDB ID and description

**Or import your own:**

* Enter a **PDB ID** and **Assembly ID** (default: 1), then click **"Import"**
* Or **upload a structure file** (.cif, .cif.gz, etc.)

### Option 2: Sequence-Based Specification

Click the **"Sequence"** tab to add sequences directly instead of using a structure.

## Select Residues

<Frame>
  <img src="https://mintcdn.com/boltzpbc/zAMCTtaZhFrbevMy/images/user-guide/protein-design/protein-design-06.png?fit=max&auto=format&n=zAMCTtaZhFrbevMy&q=85&s=efc59d51e53a9004627d582a00a6caa6" alt="Select residues for nanobody specification" width="1290" height="820" data-path="images/user-guide/protein-design/protein-design-06.png" />
</Frame>

Select the residues you want to include in your design:

* **Recommended:** ≤300 residues
* Use **CDR1**, **CDR2**, **CDR3** quick-select buttons for antibodies/nanobodies
* Or manually select by clicking and dragging on the sequence
* Selected residues are highlighted in green
* The 3D structure updates to show selected regions

**Numbering schemes:**

* **Chothia** (default) or **Kabat** numbering for antibodies/nanobodies
* Switch between schemes using the tabs above the sequence

Click **"> Continue to Design"** when done.

## Design Configuration

Configure design motifs and constraints:

<Frame>
  <img src="https://mintcdn.com/boltzpbc/kY8bkQpkfe_a5_5T/images/user-guide/protein-design/binder-3.png?fit=max&auto=format&n=kY8bkQpkfe_a5_5T&q=85&s=eb67a9b0cf2e41c3e1d50dc533621662" alt="Nanobody specification structure selection" width="2994" height="1636" data-path="images/user-guide/protein-design/binder-3.png" />
</Frame>

### Excluded Amino Acids

Specify amino acids that will not be used in designed regions (e.g., exclude Cysteine to prevent unwanted disulfide bonds).

<Frame>
  <img src="https://mintcdn.com/boltzpbc/kY8bkQpkfe_a5_5T/images/user-guide/protein-design/binder-4.png?fit=max&auto=format&n=kY8bkQpkfe_a5_5T&q=85&s=c38050b46085c176589675a49d957d99" alt="Nanobody specification structure selection" width="2990" height="1622" data-path="images/user-guide/protein-design/binder-4.png" />
</Frame>

### Create Design Motifs

1. **Select residues** on the sequence or 3D structure
2. Right-click or use the context menu to **"Replace with design motif"**
3. For CDR regions, you can specify:
   * **Fixed length** - Replace with same number of residues
   * **Variable length** - Specify a range (e.g., 10-25 residues for CDR3)

<Frame>
  <img src="https://mintcdn.com/boltzpbc/kY8bkQpkfe_a5_5T/images/user-guide/protein-design/binder-5.png?fit=max&auto=format&n=kY8bkQpkfe_a5_5T&q=85&s=fb2dd92ff7f5833c8844edb98b3307c6" alt="Nanobody specification structure selection" width="2990" height="1636" data-path="images/user-guide/protein-design/binder-5.png" />
</Frame>

<Frame>
  <img src="https://mintcdn.com/boltzpbc/kY8bkQpkfe_a5_5T/images/user-guide/protein-design/binder-6.png?fit=max&auto=format&n=kY8bkQpkfe_a5_5T&q=85&s=82198cd66d231015c21ec828a2e86531" alt="Nanobody specification structure selection" width="2998" height="1670" data-path="images/user-guide/protein-design/binder-6.png" />
</Frame>

<Frame>
  <img src="https://mintcdn.com/boltzpbc/kY8bkQpkfe_a5_5T/images/user-guide/protein-design/binder-7.png?fit=max&auto=format&n=kY8bkQpkfe_a5_5T&q=85&s=ba88599b72cbd24a7d913c569b87a122" alt="Nanobody specification structure selection" width="2990" height="1642" data-path="images/user-guide/protein-design/binder-7.png" />
</Frame>

### Motif Management

* Each motif is color-coded and shown in the sequence viewer
* Click a motif to edit it
* Click the **X** on a motif to remove it
* Summary shows total residues and number of motifs

Click **"> Create Specification"** when ready.

## After Binder Specification Creation

Once your binder specification is created, you'll see options to:

* **Generate binders with AI** - Start a virtual screen using this binder specification
* **Create Another Target** - Add another target to design binders against
* **Skip for now** - Continue later
