|Video Example|

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:

ICM Sequence Format Guide

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'

For unusual amino acids that are not in our library see section 5 below.

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.

The terminal amide has to be preserved as backbone but you can create terminal amide to side-chain crosslink via a terminal ‘residue’

e.g.

… lys{ce_Xa} …. trp cmet{hm1_Xa}

4. Terminal Designations

Terminal Type	ICM Residue Code
C-terminal amide	`conh`
N-terminal charged amine	`nh3+`
N-terminal neutral amine	`nter`

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

5. Preparing Extended Sequence Syntax for Unusual Amino Acids

Automated Processing: You do not need to manually create new entries in the icmff.res library for all unusual amino acids. ICM understands extended sequence syntax, defining unusual amino acids as modifications of natural ones. For example, 3-methoxy, 4-cyano phenylalanine is encoded as:
phe{he1_OC,hz_C#N} You can enter this text in the table to dock as shown below.

Generate Sequence Syntax for Unusual Amino Acid The mol2modres.icm script (included in $ICMHOME/bin) processes your monomer database to automatically prepare the residue definition strings.
SMILES Residue Modifiers: Prepare a sdf file of your unusual amino acids (remember to include chirality) and then run the script to output either an .sdf or .csv file. If a particular row cannot be converted, the resulting value will be left empty:
$ICMHOME/icm64 $ICMHOME/bin/mol2modres.icm unususal_amino_acid_monomers.sdf output=result.sdf You will see a new column with the code for your amino acid which you can then copy and paste into your sequence for docking.

6. 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.
To run from the command line prepare the input sequence as a sequence.se file and use _dockScan script.

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