To dock a peptide to a protein structure:

1. Setup the Docking Project and Receptor

• Setup the protein receptor the same way you would for small molecule docking.
• Prepare a table with your peptide sequence(s) to dock from Docking/Dock Peptide table.

2. Preparing a Table with Peptide Sequences

To create a table for peptide sequences, follow these steps:

Create a New Table

• Go to File > New and select the Table tab.
• Choose one string column and set the number of rows based on how many peptides you wish to dock.
• A new table will appear in the GUI.
• Rename the column containing the sequence to 'sequence' .
• Enter your peptide sequences in the format shown below:

Sequence Format Guide

Before defining sequences, check icmff.res in $ICMHOME (distribution directory) to see which residue types ICM supports. All defined residues are stored in the icmff.res file in the ICM distribution directory. It is a text file so you can view it in a text editor or grep it. Example to search for ornithine grep ornithine icmff.res and you will see the code is 'orn'

1. Standard and Advanced Numbering

• 3-Letter Codes: gly ala ser pro tyr his
• Advanced Notation: (Includes numbering, N/C-terminals, and D-amino acids)
  0 nter 1 gly 2 ala 2A Dglu 4 asp cooh

2. Specialized Bonds and Cyclization

• Disulfide Syntax: Use numerical markers in parentheses. Multiple disulfides can be encoded as (1), (2), etc.
  acet ala cys(1) ala ala cys(1) ala conh
• N-term to C-term Cycles: Use special "virtual" residues:
  nvtr ala ala ala ala cvtr

3. Crosslinks and Modifiers

Use curly braces {} for crosslinks or unusual modifications.

• Lys to Glu Link: The 'Xa' stands for crosslink 'a' replacing an atom (e.g., Nz of lysine).
  acet ala lys{nz_Xa} ala ala ala ala ala gln{he22_Xa} conh
• Unusual Residues: aba{hg1_C} ser{hg_C(=O)C)}

Note: Modifiers cannot be applied to the backbone (C, Calpha, and N atoms). Hydrogen and side-chain atoms are acceptable.

e.g.

… lys{ce_Xa} …. trp cmet{hm1_Xa}

4. Terminal Designations

Example Input File Sequence:
nh3+ nle ala ala ala ala conh

Importing Sequences (Optional)

• You can import a table from an Excel or CSV file. Make sure that the column containing the sequence is labeled 'sequence'.
• If you have a peptide loaded from a PDB file, extract its sequence:
  • Right-click on the peptide.
  • Select>Extract Sequences to Table.

3. To dock the ligand:

Docking a Peptide Table

Start Docking

• Setup the protein receptor the same way you would for small molecule docking.
• Go to Docking > Dock Peptide Table.
• Click OK to use the default docking settings.

Adjusting Docking Parameters (Optional)

• If you uncheck "dock immediately," you can modify settings before docking.
• Use the table side panel to adjust:
  • Thoroughness
  • Number of conformations

Restraining or Biasing the Peptide Structure

You can restrain or bias the ligand towards a specific secondary structure. To do this, define each residue with one of the following secondary structure types:

• H - Alpha helix
• G - 3/10 helix
• I - Pi helix
• E - Beta strand
• B - Beta-bridge
• _ - Undefined
• C - Coil