Ligand Alignment Panel

Align a set of ligand structures flexibly with torsional variation, using the best available method.

To open this panel: click the Tasks button and browse to Structure Alignment → Ligand Alignment.

This panel is docked into the Workspace by default, so you can easily switch focus from the panel to the Workspace. You can undock the panel if you want to place it somewhere else. To dock or undock the panel, use the docking button in the title bar (left of the Close button) .

  • Overview
  • Features
  • Additional Resources

Overview of Ligand Alignment

This panel brings together several methods for alignment of ligands in one place, and uses a best practices approach to choose the most appropriate method. The ligands can be similar (a congeneric series, for example, or multiple congeneric series with different cores) or diverse.

align_ligands—This program is used (a) when a reference ligand is not provided, (b) when a reference ligand is provided except when the reference conformation is sampled. It uses a variety of methods, depending on the ligand set: flexible alignment using common core snapping, least-squares alignment of common cores, or full shape-based superposition. When a reference ligand is not provided, reference ligands are chosen automatically after clustering by the largest common Bemis-Murcko scaffold.

When the ligands are aligned, two entry properties are added that give information on the alignment. Alignment Method records information on which method was used to align the ligands. Alignment Reason gives information on why another method was used instead of the default: for example if core snapping fails in align_ligands. Other entry properties may also be present, depending on the method used.

flex_align—This program is used when a reference ligand is defined and the conformation of the reference is sampled.

tug_align.py—This program is used for ligands that contain macrocycles.

For more details on the methodology, see Ligand Alignment Methodology.

Ligand Alignment Panel Features

The dependencies between the features are complex, so the conditions on when options are shown or not are given with the description, as necessary. If no conditions are given, the feature is always shown in the panel.

Align ligands from option menu

Choose the structure source for the alignment.

  • 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.
  • Workspace (n included entries)—Use the entries that are currently included in the Workspace, treated as separate structures. The number of entries in the Workspace is shown on the menu item. An icon is displayed to the right which you can click to open the Project Table and include or exclude entries.
  • 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 or include 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.

Ligands contain macrocycles option

Specify whether the ligands contain macrocycles. The choice affects the features available for setting up the alignment. It also enables the alignment to be distributed over multiple processors, which you can set up in the Job Settings Dialog Box.

Reference options

Choose an option for selection of the reference ligand. The choice affects the other features available.

  • Automatic—allow the reference ligand to be chosen by the program.
  • User-specifed—choose the reference ligand from the set of ligands to be aligned. The Ligand option menu and search button, and Sample reference ligand conformation option are displayed below these options.

These options are available if the ligand does not contain macrocycles.

Reference option menu and search button

Choose the reference ligand from the option menu, or click the search button to search for the reference ligand by row number, entry title, or both. Ligands in the project are listed by project row number and title; ligands from file are listed by title only.

The default selection of reference ligand depends on the ligand selection and inclusion:

  • If the ligand source is the selected entries, the default reference ligand is the one in the Workspace if only one is included
  • If the ligand source is the Workspace, the reference ligand is the selected ligand if only one is selected
  • Otherwise, the first ligand in the set is the default reference ligand.

This feature is present when a user-specified reference is selected or when the ligands contain macrocycles.

Conformation options

Specify the reference ligand substructure or conformation that is to be used for alignment, for a non-macrocycle user-specified reference.

  • Constrain common substructure—Specify the substructure of the reference ligand that is used in the current conformation when the other ligands are aligned to it. The choices are Largest common Bemis-Murkco scaffold, MCS (maximum common substructure), and SMARTS. For SMARTS, a set of tools to specify the SMARTS pattern is displayed (see below for a description).

  • Sample reference ligand—Replace the primary reference structure with a sampled conformer that yields the best shape-based superposition to the corresponding input structure. This option is useful when the reference conformation is not known.

Common scaffold menu

Specify how the common scaffold is determined for macrocycles. The choices are MCS (maximum common substructure) and SMARTS. For SMARTS, a set of tools to specify the SMARTS pattern is displayed (see below for a description).

SMARTS text box and buttons

These tools allow you to provide a SMARTS pattern for the common scaffold. You can:

  • Type or paste the SMARTS pattern into the text box.

  • Click Get from Selection to create a SMARTS pattern for the selected atoms in the Workspace. The pattern replaces the contents of the text box.

    Hydrogens are not included in the pattern (regardless of the Maestro preference), as the inclusion of many hydrogens can significantly slow down the alignment. Hydrogens on terminal heavy atoms are aligned by default, and other hydrogens are usually aligned well, so it is not necessary to include hydrogens in the SMARTS pattern unless there is a specific reason to do so.

  • Click Sketch to draw a 2D structure to generate the SMARTS pattern, which replaces the contents of the text box. See 2D Sketcher Panel for more information on the sketching tools.

The SMARTS pattern in the text box can be edited as needed.

Specify receptor option

Specify a receptor for a macrocycle alignment. The receptor is used to constrain the macrocycle conformations to avoid clashes. When you select this option, the Get receptor from option menu is displayed, to choose the source of the receptor.

Get receptor from option menu

Choose the structure source for the receptor.

  • 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. When this option is selected, a Load button is displayed to the right.
  • Workspace (n included entries)—Use the entries that are currently included in the Workspace, treated as separate structures. The number of entries in the Workspace is shown on the menu item. 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.
Load button

Load the receptor from the Project Table or Workspace into the panel.

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.

Advanced Options link

Specify options for the alignment method. Opens the Ligand Alignment - Advanced Options Dialog Box.

Not present for ligands with macrocycles.

Overwrite existing entries option

Overwrite the existing entries with the aligned entries. This option sets the Incorporation setting in the Job Settings Dialog Box to Replace existing entries. Clear this check box to incorporate the aligned ligands as new entries.

Job toolbar

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

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

You can save and load alignment settings using the Settings button menu .

  • To save settings, choose Save Panel Options, and enter a name in the dialog box. If you want to make these settings your defaults, select Set as user default.
  • To load settings, choose Load Panel Options. The Manage Ligand Alignment Options dialog box opens, in which you can select and apply a set of saved options, delete or replace any set of options, reset to the Maestro default options, and rearrange the list of option sets.
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. It also displays a progress bar for the job.

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

Videos

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