Peptide Docking Panel

This panel allows you to set up and run a job to dock peptides to a protein using Glide. The protein is treated as a rigid structure, but with some softening of the potentials for flexibility; the peptides are treated as flexible structures.

To open this panel, click the Tasks button and browse to Biologics → Peptide Docking.

  • Using
  • Features
  • Additional Resources

Using the Peptide Docking Panel

Peptide docking is done with Glide, which treats the receptor as a rigid structure but with softening of the potentials in the active site region to simulate small adjustments of the receptor to the ligand. The peptide ligands are treated flexibly. As peptides are very flexible compared to more typical non-peptide ligands, the Glide docking is performed with increased sampling, and several docking runs are done for each peptide, with different input conformations, to further increase the sampling. The peptides that are built do not have capping groups, and by default are in zwitterionic form, i.e. with charged termini. For more information on the Glide docking process, see the Glide User Manual — Contents.

With the Glide technology, peptides that have a diameter greater than 80 Å cannot be docked due to the grid box size limit. This corresponds to a linear peptide of about 16 residues. Glide also restricts the number of rotatable bonds to 100, due to the rapid increase in the number of conformations with the number of rotatable bonds. The maximum peptide length that can be docked in practice will depend on the conformation and the residue types.

Docking peptides is time consuming as there are many conformations to explore. A single peptide can take a few hours to dock. It is recommended that you run the job across multiple processors if you can, especially if you want to dock several peptides. The number of processors and the number of subjobs can be specified in the Job Settings Dialog Box.

The job output is a file containing the receptor and the poses of the docked peptides (in a “pose viewer” file). You can step through the poses in the presence of the receptor using the Pose Viewer Panel.

To run peptide docking from the command line, you can use the following command. Run the command with -h for more information.

$SCHRODINGER/pipeline

To write out input files, click the arrow next to the Settings button,

and choose Write (more...).

For information on command options, see vsw Command Help.

Peptide Docking Panel Features

 

Binding Site section

In this section, you select the binding site for the peptides on the protein. This can be a previously defined site or a site that you define using the Workspace structure. The grids that are generated for the docking are centered on the location that you choose for the binding site.

Region options

Choose the source of the grid for docking to the binding region.

  • Define grid—define a new grid based on the Workspace receptor. The Centroid and Dimensions controls are displayed below when you choose this option.

  • Use existing grid—choose a recently used grid from the option menu or choose Locate file to find a grid file. The File name text box and Browse button are displayed below when you choose this option. The recently used grid list is updated when you define a new grid or you locate an existing grid. The most recent grid is selected by default.

Centroid options

Choose the centroid of the binding site, on which the grid is centered. Only available if you selected the option to define a grid.

Centroid of Workspace ligand option and Pick option

Center the binding site and thus the docking grids at the centroid of the ligand molecule that you pick in the Workspace. Use this option if your receptor has a ligand that occupies the binding site. To pick the ligand molecule, select Pick and click on a ligand atom in the Workspace. Information on the ligand is shown in the box once you have picked the ligand.

Centroid of selected residues option and Select Residues button

Set the center of the binding site at the centroid of a set of residues that you select. This option is useful if you don't have a bound ligand. You should choose residues whose centroid is approximately where the centroid of a bound ligand should be.

To select the residues:

  1. Click Select Residues. The Atom Selection Dialog Box opens.
  2. Click the Residues tab.
  3. Pick the residues in the Workspace.
  4. Click Add, then click OK.
X, Y, Z, text boxes

These noneditable text boxes show the coordinates of the center of the binding site. They are displayed once you have defined the centroid.

Dimensions options

Define the box in which the peptide ligands can be placed during docking (the outer box or grid box). Only available if you selected the option to define a grid. There are two options:

Defined automatically based on peptide ligand set

Select this option if you want the box size to be determined automatically once the peptide ligand set is defined. This option ensures that the box size is no larger than is necessary, and is the default.

Outer box fully accommodates linear peptide of N residues

Specify the maximum number of residues in the peptides that you want to dock. This option sets the box size so that it accommodates the longest peptide in a linear conformation. The box may be larger than necessary to dock the actual conformations. The maximum possible linear peptide length is 15 residues, but it is likely that such peptides could have too many rotatable bonds to be docked with Glide.

This text box is updated to display the number of residues that fit inside the box when you set the centroid and a default box is created.

File name text box and Browse button

Enter the grid file name in this text box, or click Browse and navigate to the grid file. The name of the grid file you selected is displayed in the text box. Only available if you selected the option to use an existing grid.

Define peptides to dock section

In this section you choose the peptides to dock, which can be taken from the Project Table or a file, or can be entered by hand.

Add sequences from buttons

To add peptides to the list, click one of the buttons. You can click any of the buttons multiple times, to add peptides to the list.

  • File—Add peptide sequences from a file. Opens a file selector in which you can locate and open the file. The file must be a plain text file (.txt) with one sequence per line, or a PDB file (.pdb) with a single structure.
  • Project Table—Use the peptide sequences from the selected entries in the Project Table. You should select the entries in the Project Table first. Only the sequences are used: the structures are generated as part of the process.
  • Text—Enter the sequence of the peptide to be docked as a string of one-letter standard residue codes. Opens a dialog box in which you can type in the sequence.
Peptide table

The peptides to be docked are listed in this area. You can select multiple rows to remove them. You can edit individual rows by double-clicking on the row, then editing the text. If the sequence is colored red, it contains an invalid single-letter residue code, and must be corrected.

Delete and Delete All buttons

Remove the selected peptides or all peptides from the list.

Export button

Export the sequences from the peptide list to a plain text file, one sequence per line.

Docking options and settings

Set options for conformer generation, docking runs and results.

When generating conformers from sequences options

Select options for the types of conformers that can be generated from the sequences.

  • Neutralize termini—Neutralize the terminal acid and amine groups, rather than allowing them to be charged (zwitterionic). Capping groups (NMA and ACE) are not added to the termini. This option is turned off and cannot be changed in the current release; however capping groups are added if the input sequences are added as text.
  • Allow cis amide bonds—Allow peptide linkages in the cis conformation as well as the usual trans conformation.
Number of poses to return for each independent docking run box

Specify the number of poses to return from each independent docking run. The poses from each run are combined and sorted to give a set of poses for the peptide. If the number specified is too small, you risk losing good poses. For example, if the first ten poses from a particular run are lower than any of the poses from the other runs, and you only allow one pose from each run, you would lose nine of the best poses.

Scoring method options

Set options for scoring the docked poses. The scores are estimates of the binding free energy, and are returned as properties of the docked poses.

MM-GBSA option

Use the MM-GBSA ligand binding energy as the score. This option involves an extra calculation to evaluate the binding free energy in implicit solvent, and is therefore more expensive, but more accurate. For more information on the MM-GBSA method used, see Prime MM-GBSA.

Glidescore option

Use the GlideScore value from the docking run to score the peptide poses. This is the Glide SP docking score, and is produced automatically as part of the docking run.

Job toolbar

Manage job submission and settings. See Job Toolbar for a description of this toolbar.

The Job Settings button opens the Peptide Docking - Job Settings Dialog Box, where you can make settings for running the job.

Status bar

The status bar displays information about the current job settings and status for the panel. The settings includes the job name, task name and task settings (if any), number of subjobs (if any) and the host name and job incorporation setting. The job status can include messages about job start, job completion and incorporation.

Use the Reset button to reset the panel to its default settings and clear any data from the panel. You can also reset the panel from the Job toolbar.

The status bar also contains the Help button , which opens the help topic for the panel in your browser. If the panel is used by one or more tutorials, hovering over the Help button displays a button, which you can click to display a list of tutorials (or you can right-click the Help button instead). Choosing a tutorial opens the tutorial topic.

Tutorials

Related Topics