XGlide Panel

Run Glide docking jobs in which multiple ligand sets are docked to multiple receptors.

To open this panel: click the Tasks button and browse to Receptor-Based Virtual Screening → Cross Docking.

Using
Features
Additional Resources

Using the XGlide Panel

This panel is intended for the docking of ligands to multiple receptors. One of its primary uses is for cross-docking, where you might have several ligand-receptor complexes for the same target, and you want to dock each reference ligand into each receptor.

If you want to align the receptors before docking, you can do so. Ligands that are included with the receptor are aligned, so they can be used for reference ligands. If you have a mix of complexes and apo structures, you can use the ligands from the complexes to define a common grid center for all the receptors.

The output from the docking job is written to the working directory. You must import the poses or complexes if you want to include them in the project.

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 xglide.py Command Help.

Receptors tab

In this tab you define the receptors that you want to use for docking.

Receptors table

This table lists the receptors to which ligands will be docked. The receptors can be defined by a complex structure, a receptor structure, or a previously prepared receptor grid. The Type column indicates whether a complex (with ligand), a receptor (without ligand), or a grid was specified. The Ligand molnum column shows the ligand molecule number for a receptor defined by a complex. The ligand is automatically detected by applying the specified minimum and maximum number of atoms. For receptors, this column reports None and for grids, it reports NA (not applicable).

Ligands from complexes are automatically used as reference ligands and associated with the appropriate receptor.

Add Receptor button

Add a receptor to the table. Opens a file selector, in which you can navigate to a Maestro file, to select the receptor. All molecules in the structure are treated as part of the receptor. This is a way of selecting an apo protein, or a protein that has cofactors that are not the ligand.

Add Complex button

Add a receptor-ligand complex to the table. Opens a file selector, in which you can navigate to a Maestro file, to select the file. The ligand is detected automatically, and is used to determine the center of the grid.

Add Grid button

Add a precomputed grid to the table. Opens a file selector, in which you can navigate to a grid file (.grd or .zip), to select the file.

Remove button

Remove the selected receptor from the table.

Align receptors and complexes to first in list option

Perform a structural alignment of the receptors and complexes, with the utility structalign. All atoms are included in the alignment. The first of the receptors or complexes is used as the reference, and the rest are aligned to the first. If you align the binding sites, you will not be able to use reference ligands from files, because the external ligands are not aligned. You can, of course, use the native ligand that is included in the complex as a reference ligand.

Ligands tab

In this tab you specify the ligands to be docked. You can also specify reference ligands and associate ligands with a receptor.

Ligands table: This table lists the ligand files that are to be used in docking. The Is reference column specifies whether the file contains reference ligands. The reference ligands are used to define the active site and also for computing RMSD values. If you aligned the receptors, you should not specify reference ligands by this means. The Receptor association column specifies which of the receptors is associated with the ligand file. These ligands can be used to define the grid center for the receptor. When docking, you can restrict the input ligands to those associated with a receptor. To set the association, double-click in the table cell and choose a receptor from the option menu that is displayed.
Add button: Add a ligand file to the table. Opens a file selector, in which you can navigate to a Maestro file that contains ligands.
Remove button: Remove the selected row (ligand file) from the table.
Prepare ligands with LigPrep option: Run LigPrep to prepare 3D, all-atom structures from the input ligands. LigPrep is run with the default options.
Use Epik option: Use Epik to generate ionization and tautomeric states. Epik is run with the default options, so no metal-binding states are generated.

Grid Generation tab

In this tab you set options and parameters for grid generation. Preexisting grids are not affected by the options in this tab.

Grid center options

Select an option to define the center of the grid for each of the receptors or complexes for which grids are needed.

Set common grid center for all receptors at centroid of all reference ligands—Define a common grid center for all the receptors that is at the centroid of all the reference ligands. This should only be done if the binding sites are aligned, so that the receptors are in a common frame of reference. It is probably not useful to set this option if you also have preexisting grids, because the grid center is not changed for preexisting grids.
Set grid center for each receptor at centroid of associated reference ligands for that receptor—Set the grid center independently for each receptor, at the centroid of the reference ligands that are associated with that receptor.
X, Y, Z coordinates—Set the grid center to the Cartesian coordinates specified in the text boxes.
Use SiteMap to locate active sites—Run SiteMap for each receptor to locate active sites. The top-scoring site is used, and the grid center is placed at the centroid of the site points.

Inner box size text box

Set the dimension of the (cubic) box to which the center of the ligand is confined during docking. The center of the ligand is the midpoint of the line joining the two atoms that are furthest apart.

Outer box size text box

Set the dimension of the (cubic) box on which the grid is evaluated.

Docking and Output tab

In this tab you specify how to dock the ligands and what output to produce.

Dock ligands option

If this option is selected, the ligands are docked to the receptors as specified in this tab. If it is not selected, the grids are generated, and the ligands are prepared (if the option to do so is selected).

Precision options

Choose a docking precision option:

HTVS (high throughput virtual screening): High-throughput virtual screening (HTVS) docking is intended for the rapid screening of very large numbers of ligands. HTVS has much more restricted conformational sampling than SP docking, and cannot be used with score-in-place. Advanced settings are not available for HTVS, but are fixed at predetermined values.
SP (standard precision): Standard-precision (SP) docking is appropriate for screening ligands of unknown quality in large numbers.

For more information on the Glide docking process, see Glide Methodology.

Write XP descriptors option

Write out the XP descriptors to the pose file. Only available if you select XP for the precision.

Ligand vdW scale factor text box

Scale the van der Waals radii of the nonpolar ligand atoms by the amount specified in the text box.

Cutoff for a 'good' RMSD text box

Specify the cutoff for defining a good (satisfactory) RMSD value from the reference ligands for a pose. This criterion is used to evaluate the results.

Dock only the ligands associated with each receptor (native only) option

Dock only the ligands from the files for which an association with a receptor was specified in the Ligand table.

Generate top complexes option

Generate complexes for the top poses, and write them to the file jobname_workdir/jobname_topcomplexes.maegz. The complexes for each receptor are in a contiguous block, and they are sorted by docking score within each block.

Max. complexes per receptor text box

Specify the maximum number of complexes to generate for each receptor.

Job toolbar

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

The Job Settings button opens the XGlide - 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.