MCS Docking Ligand Alignment Panel
Align a set of congeneric ligands to a dynamically adjustable set of reference ligands using Glide docking with MCS core constraints.
To open this panel: click the Tasks button and browse to Structure Alignment → MCS Docking Ligand Alignment.
- Overview
- Using
- Features
- Additional Resources
Overview of MCS Docking Ligand Alignment
MCS docking ligand alignment aligns a set of input ligands to a set of reference ligands, by applying core constraints between the ligand to be docked and one of the reference ligands. The constraints are based on the maximum common substructure (MCS), and the reference ligand with the best match to the input ligand is chosen for the core constraints. The ligand is then docked to the receptor grid for the reference ligand, which can be different for each receptor. If the docking produces no poses, flexible ligand alignment is tried by default as a fallback (using the phase_align_core Command Help methods).
The purpose of the alignment is to provide a set of congeneric ligands that are well aligned to each other and the receptor for determination of relative binding affinities, for example by FEP+.
Using the MCS Docking Ligand Alignment Panel
MCS docking ligand alignment is designed for alignment of a relatively small number of ligands (a few hundred, perhaps) to a reference set. It is not a high-throughput tool, for which you should use Glide docking or Phase. As the intention is to provide a set of congeneric ligands that are well aligned for input into the FEP+ workflow (or Prime MM-GBSA), the ligands should have a substantial common substructure.
The output from the job is a pose-viewer file (jobname_pv.maegz) or an extended pose-viewer file (jobname_epv.maegz), depending on the number of receptors; the receptors are first, followed by the ligand poses. The best pose for each ligand is the one that is written out. The reference ligand and the receptor used for each ligand are identified in Maestro properties.
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.
MCS Docking Ligand Alignment Panel Features
- Receptor section
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Define the default receptor grid, from a file or the Workspace.
- Receptor grid option menu
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Choose the source of the receptor grid.
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File—use an existing grid. The File name text box and Browse button are displayed so you can select the grid file.
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Create from Workspace—create a new grid from the receptor in the Workspace. The Set Up Grid button is displayed so you can create the grid.
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- File name text box and Browse button
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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. Allowed file types are: Glide grids (
.grd,.zip). - Set Up Grid button
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Set up the grid from the Workspace structure. The reference ligand and the receptor that you display in the Workspace for grid setup can come from different project entries or the same entry.
Clicking the button opens the MCS Create Receptor Grid dialog box, which has the standard Glide features for setting up a grid (see the Site tab in the Receptor Grid Generation Panel topic). Click OK to run the job to set up the grid. Progress is shown next to the button.
- Ligands for Alignment section
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Specify the source of the ligands that you want to align to the references.
- Reference Ligands section
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Specify the source of the reference ligands and set options for these ligands.
- References option menu
- References option menu
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Choose the structure source for the reference ligands.
- Project Table (selected entries)—Use the entries that are currently selected in the Project Table.
- File—Use the specified file. When this option is selected, the File name text box and Browse button are displayed.
- File name text box and Browse button
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Enter the file name for the reference ligands 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.
- Allow docked ligands to become reference ligands option
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As ligands are docked, add them to the list of reference ligands if they have sufficient similarity to the reference set. These ligands can then be used as references for subsequent ligands.
- Docking-based alignments only option
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Align the ligands to a reference using docking with core constraints only. If unchecked, use flexible ligand alignment as the fallback if docking produces no poses (the default).
- Skip ligands that have MCS similarity less than text box
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Ligands that have an MCS similarity less than the specified threshold are not docked or included as references (if the option is selected). The similarity is the Tanimoto similarity based on the number of atoms in the MCS and the numbers of atoms in the reference and input ligands.
- Advanced Options button
-
Open the Advanced Options - Reference Ligands dialog box so you can choose a receptor grid for each reference ligand.
Manage job submission and settings. See Job Toolbar for a description of this toolbar.
The Job Settings button opens the MCS Docking Ligand Alignment - Job Settings Dialog Box, where you can make settings for running the job.
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.
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.