How to undertake peptide docking to a receptor in ICM?

[Andrew Orry]

Q. How to undertake peptide docking to a receptor in ICM?

A.

Watch a video example here.

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:

Example Sequence Format:

• gly ala ser pro tyr his
• or more advanced with numbering, N- and C-terminal and D-amino acids 0 nter 1 gly 2 ala 2A Dglu 4 asp cooh
• disulfide syntax is: acet ala cys(1) ala ala cys(1) ala conh - multiple disulfides can be encoded with (1) (2) etc...
• To make a cycle N-term to C-term you can use special 'virtual' residues: nvtr ala ala ala ala cvtr
• To make lys to glu link: acet ala lys{nz_Xa} ala ala ala ala ala gln{he22_Xa} conh - 'Xa' stands for crosslink 'a' replacing an atom, e.g. Nz of lysine. Multiple x-links can be applied with Xb, Xc

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