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XP Visualizer Panel |
This panel provides a way to visualize and analyze the results of a Glide XP docking run. The panel's main functions are:
To open the XP Visualizer panel, you can:
Choose Applications → Glide → XP Visualizer in the main window.
To generate results that can be used with the Glide XP Visualizer, you must select Write XP descriptor information in the Settings tab of the Ligand Docking panel, and Write pose viewer file in the Output tab of the Ligand Docking panel when you run the XP docking job.
Note: To generate XP descriptor information, you must have a license for this feature.
Click Open to load a pose-viewer file that includes XP descriptors. When you load the file, you are prompted to choose an activity property to display in the table. If you don't want to display an activity property, click Cancel.
Once the files have been loaded, all of the ligands are loaded into the
table, with the name of the ligand in the far left column (light blue
background), along with the XP terms in the rest of the columns (light gray
background). If the same ligand name is listed twice in the pose viewer file,
then a -N is added to the ligand name, where N is an
integer starting with 2 that is incremented for each successive instance of a
ligand name.
To load descriptors generated by an older version of Glide, select .xpdes and click Open to load a
descriptor file and its associated pose viewer file. A file selector opens, in
which you can navigate to the desired .xpdes file.
To sort the rows of the table by the values in a column, click on the column heading. There are three sort settings: ascending (+), descending(-), and the original pose viewer order. These settings can be changed by successively clicking on the column heading. One column can be sorted at a time.
Clicking on cells produces two different functions depending on the cell type:
Cells that have a gray border around them indicate XP term values for which a visualization exists. By clicking on one of these cells, the border is enlarged (to indicate that the cell is selected) and the visualization is displayed in the Workspace. Clicking again removes the visualization. These visualizations are different depending on the XP term and are described below.
You can select multiple ligands by clicking in the Name column, using shift-click and control-click. If Selected ligands is selected, then Maestro shows the selected ligands and the view changes each time the selection is changed. If you select more than 100 ligands, a warning is posted, and Selected ligands is turned off.
Clicking Selected Only when there are multiple ligands selected displays only the selected ligands in the table. The sorting mechanisms now work exclusively on the ligands shown in the table. The All button is used to show all ligands in the table.
You can step through ligands with the Left Arrow and Right Arrow keys. If a cell is selected, the arrow keys move up or down the column for that cell, displaying the visualization if a cell has an associated visualization.
The Glide XP Visualizer provides the following features for control of the visualization. Below these is the table of ligands and XP terms, which is described in the next section.
When opening a file, open an .xpdes file rather than a pose
viewer file.
Opens a file chooser, in which you can navigate to and select the
file that contains the XP descriptors. By default this is the pose viewer file
from the docking run. If the .xpdes option is selected,
the file chooser allows you to select an .xpdes file.
When the file is opened, the name is displayed in the File text box, and the title of the receptor entry is
displayed in the Receptor text box.
The File text box displays the name of the XP descriptor file used for the visualization. The Receptor text box displays the title of the receptor entry. The button to the left of the Receptor text box is for display of the receptor.
Change the view so that the ligands that are displayed occupy the entire Workspace.
These options control what is displayed in the Workspace
Selected ligands—Display the ligands that are selected in the table. If this option is selected, the Workspace is updated whenever the selection of ligands is changed.
Warning:If multiple ligands are selected, changing the view might take a considerable amount of time. Unless it is necessary to view many ligands at once, it is recommended that this option is not used.
XP Waters—Waters are shown as small red spheres in the visualizations and can be displayed or hidden using this option. By default, waters are displayed.
Hydrophobic/philic map— Hydrophobic and hydrophilic surfaces can be shown in the visualizations by selecting this option. The first time this option is selected, the hppmap job is run, and the button flashes until the job finishes. The surfaces are stored for subsequent use.
Similarities—Display the similarity of each ligand to the selected ligand, in the Similarity column of the table. The similarity is the Euclidean distance in XP descriptor space. These values are only displayed if there is a single ligand selected.
Relative scores—Display scores relative to the best score for each descriptor that was obtained by docking a special set of fragments, These fragments were chosen to maximize the values of each of the XP descriptors. They can only be docked by running the Virtual Screening Workflow (VSW); to do so, you must select Compute maximum values by docking fragments in the VSW - Docking Options dialog box. The fragments are listed in a separate section of the Ligands table, and are displayed in the Workspace with purple carbons, to distinguish them from the ligands.
Set the column widths to a uniform, narrow width. This allows all the columns to be viewed without making the panel wider.
Opens a dialog box in which you can rearrange the order of the columns. You can select multiple columns and move them to the top or bottom of the list, or move them up or down in the list.
Color the cells in the table by their numerical values.
Open the Edit Conditional Coloring dialog box, in which you can set up the coloring scheme for each XP term.
These buttons control what is visible in the Ligands table. By default, only the first 100 ligands are displayed.
All— This button shows all the ligands in the pose-viewer file in the table.
Selected Only— This button shows only the selected ligands in the table. The sorting mechanisms work exclusively on the group of ligands shown in the table. This function can be used to exclude ligands from the screening process based on the visualization.
Export the information shown in the table to a CSV file. Opens a file chooser, in which you can navigate to a location and name and save the file. If you want to export data for a selection of ligands, select them in the table and click Selected Only before clicking Export.
Export structures from the table to a Maestro file, along with the receptor structure. The receptor is the first structure, followed by the ligands, just as in a pose-viewer file. All selected ligands are exported, or if there is no selection, all ligands that are shown in the table are exported.
Clear all information from the panel.
The XP terms and a description of their visualizations is given below. In the visualizations, hydrogen atoms are not generally displayed, and the ligand carbon atoms are colored green.
| XP Term | Description | Visualization |
|---|---|---|
| GScore | Total GlideScore; sum of XP terms excluding Epik state penalties | None |
| DockScore | Total docking score; sum of XP terms. | None |
| LipophilicEvdW | Hydrophobic potential from the receptor at ligand atoms that are considered to be hydrophobic. | None |
| PhobEn | Hydrophobic enclosure reward | Hydrophobic atoms on the protein that enclose hydrophobic groups on the ligand are displayed in gray in CPK representation. Hydrophobic atoms on the ligand are displayed in ball and stick representation. |
| PhobEnHB | Reward for hydrophobically packed H-bond | H-bonds are displayed as pink dotted lines. Hydrophobic atoms on the protein that enclose hydrophobic groups on the ligand are displayed in gray in CPK representation. Hydrophobic atoms on the ligand are displayed in ball and stick representation. |
| PhobEnPairHB | Reward for hydrophobically packed correlated H-bonds | H-bonds are displayed as pink dotted lines. Hydrophobic atoms on the protein that enclose hydrophobic groups on the ligand are displayed in gray in CPK representation. Hydrophobic atoms on the ligand are displayed in ball and stick representation. |
| HBond | ChemScore H-bond pair term | Hydrogen bonds are displayed as yellow dotted lines. Only those hydrogen bonds that contribute to the XP GlideScore are shown. |
| Electro | Electrostatic rewards | Relevant atoms in the ligand are displayed in ball-and-stick representation. |
| Sitemap | Sitemap ligand/receptor non-H-bonding polar/hydrophobic and hydrophobic/hydrophilic complementarity terms | Hydrophobic (orange) and hydrophilic (turquoise) surfaces are displayed, representing the field of the receptor. These are the same as the Maestro Hppmap surfaces. |
| π Cat | Reward for pi-cation interactions | The relevant aromatic groups in the protein are displayed in CPK representation and in the ligand in ball and stick representation. |
| ClBr | Reward for Cl/Br in hydrophobic environment that pack against Asp/Glu | None |
| LowMW | Reward for ligands with low molecular weight | None |
| Penalties | Polar atom burial and desolvation penalties, and penalty for intra-ligand contacts | Atoms are labeled with the penalties. The labels and their descriptions and
the associated visualizations are as follows:
Twisted amide linkages in the ligand are also displayed in ball-and-stick, but not labeled. |
| HBPenal | Penalty for ligands with large hydrophobic contacts and low H-bond scores | None |
| ExposPenal | Penalty for solvent-exposed ligand groups; cancels van der Waals terms | The molecular surface of the protein around the ligand is displayed as a semi-transparent surface. Ligand groups that are exposed are rendered in ball-and-stick representation |
| RotPenal | Rotatable bond penalty | Rotatable bonds in the ligand are displayed in tube representation. |
| EpikStatePenalty | Epik state penalties for ionization or tautomeric states that dock in preference to the most common state at physiological pH. If the ligand binds to a metal, the metal-binding penalties are also included. | None |
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