Macrocycle Docking Panel (Beta)

Dock macrocyclic ligands to a receptor using Prime macrocycle sampling and Glide docking.

To open this panel, click the Tasks button and browse to Prime → Macrocycle Docking.

  • Overview
  • Using
  • Features
  • Additional Resources

Overview of Macrocycle Docking

Macrocycle Docking combines Prime macrocycle conformational sampling (Prime Macrocycle Sampling Panel) with Glide docking to generate high-quality binding poses for macrocyclic ligands. Ring conformers are pre-sampled with Prime-MCS and filtered by energy. Each remaining ring conformer is docked individually with Glide, keeping the ring fixed to prevent conformational dilution and maximize R-group sampling. The top pose from each Glide docking job is rescored with a composite scoring function that incorporates the Glide energy and the Prime implicit solvent energy of the macrocycle-receptor complex. This approach generates higher-quality poses than Glide macrocycle mode, at the expense of more compute time (approximately 2-3x).

Using the Macrocycle Docking Panel

Use this panel to dock macrocyclic ligands to a rigid receptor. Both the receptor and ligands must be prepared before docking. The receptor should be prepared with the Protein Preparation Workflow Panel, and the ligands should be prepared with LigPrep Panel. To set up a macrocycle docking job:

  1. Load the receptor structure into the Workspace and click Load Workspace to set it as the receptor.
  2. Choose how to define the center of the docking grid from the Box center option menu. Select Centroid of ligand to use a template ligand in the receptor, or Centroid of selected residues to define binding site residues by selection or ASL expression.
  3. Select the ligands to dock from the Ligands to dock option menu. You can select entries from the Project Table or browse for a file.
  4. Choose the ring conformer sampling method. Automatic uses Prime-MCS to generate conformers. If you are docking a single ligand and have pre-generated conformers, select File and browse for the conformers file. Ring conformer sampling is set to Automatic when multiple ligands are loaded.
  5. Set the maximum number of output poses per ligand in the Max poses to return text box. The default is 10.
  6. Choose the force field. OPLS4 is recommended. You can use a customized OPLS4 parameter set if available. The job can be parallelized across multiple CPUs. Set the host and number of processors in the Job Settings. Output files are written to the working directory. The output structure file (jobname-out.maegz) contains the docked poses, and a CSV file (jobname.csv) contains the scores.

To run macrocycle docking from the command line, see

To write out the input file and a script for running the job from the command line, click the arrow next to the Settings button and choose Write. For information on command usage and options, see macrocycle_docking.py Command Help.

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Macrocycle Docking Panel Features

Receptor text and load button

Load a receptor structure from the Workspace.

Box center option menu

Choose how to define the center of the docking grid.

Pick option

Select this option to pick a ligand atom in the Workspace to define the box center. Only present when Centroid of ligand is selected from the Box center option menu.

Binding site text box and Add Workspace Selection link

Enter an expression to define the binding site residues, or click the Add Workspace Selection link to populate the text box from the current Workspace selection. Only present when Centroid of selected residues is selected from the Box center option menu.

Ligands to dock option menu

Choose the structure source for the current task.

  • Project Table (n selected entries)—Use the entries that are currently selected in the Project Table or Entry List. The number of entries selected is shown on the menu item. An icon is displayed to the right which you can click to open the Project Table and select entries. When this option is selected, a Load button is displayed to the right.
  • File—Use the specified file. When this option is selected, the File name text box and Browse button are displayed.
Open Project Table button

Open the Project Table panel, so you can select the entries for the structure source.

File name text box and Browse button

Enter the file name in this text box, or click Browse and navigate to the file. The name of the file you selected is displayed in the text box.

Ring conformer sampling option menu

Choose the method for generating macrocycle ring conformers. Select Automatic to use Prime MCS to generate conformers, or File to provide a file of pre-generated conformers. Not available when multiple ligands are loaded.

Browse button

Browse for a file of ring conformers in Maestro format. Only present when File is selected from the Ring conformer sampling option menu.

Max poses to return text box

Specify the maximum number of output poses per ligand. The range is 1 to 1000, with a default of 10.

Force field option menu

Choose the force field for the current task. The choices are OPLS_2005 and OPLS4.

Use customized version option

Use your customized version of the OPLS4 force field, rather than the standard version in the distribution. Only available when you choose OPLS4 from the Force field option menu and you have the appropriate license. This option is set by default to the value of the Use custom parameters by default option in the Preferences panel, under Jobs - Force field, when the current panel is opened. The default directory for the customized version can also be specified as a preference, in the same location.

If the customized version is missing or invalid, the text of this option turns orange and an orange warning icon is displayed to the right, with a tooltip about the problem.

Parameter set button

Select the set of custom parameters for the OPLS4 force field. Opens the Set Custom Parameters Location Dialog Box. Only available when you choose OPLS4 from the Force field option menu and you have the appropriate license.

Job toolbar

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

Status bar

Use the Reset button to reset the panel to its default settings and clear any data from the panel. If the panel has a Job toolbar, you can also reset the panel from the Settings button menu.

If you can submit a job from the panel, the status bar displays information about the current job settings and status for the panel. The settings include 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.

The status bar also contains the Help button , which opens an option menu with choices to open the help topic for the panel (Documentation), launch Maestro Assistant, or if available, choose from an option menu of Tutorials. If the panel is used by one or more tutorials, hover over the Tutorials option to display a list of tutorials. Choosing a tutorial opens the tutorial topic.

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