SiteMap Panel
SiteMap is a tool for finding, visualizing and evaluating protein and nucleic acid binding sites.
To open this panel: click the Tasks button and browse to Structure Analysis → Binding Site Detection.
- Overview
- Using
- Features
- Additional Resources
Overview of SiteMap
Sites are represented as collections of site points at or near the surface of a protein that are contiguous or are separated in solvent-exposed region by short gaps that could plausibly be spanned by ligand functionality. The visualization uses a grid of points to identify potential hydrophobic and hydrophilic regions; the hydrophilic regions are further classified into hydrogen-bond donor, hydrogen-bond acceptor, and metal-binding regions, and the surface of the protein is contoured. These regions can be displayed in the Workspace.
Key properties, including an overall SiteScore that gauges the propensity of the site to bind ligands tightly, are returned to the Project Table. Other properties measure the exposure of the site to solvent, its degree of enclosure by the protein, the tightness with which the site points interact with the protein ("contact"), the degree of hydrophobicity of the site, the degree of hydrophilicity, the balance between the two, and the extent to which a ligand would be likely to donate, rather than accept, hydrogen bonds ("don/acc"). SiteScore and the contact, phobic, and philic properties are expressed relative to the average value found for a large number of protein sites that bind ligands tightly.
Using the SiteMap Panel
To set up a SiteMap calculation:
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Display the protein in the Workspace. If you want to find all sites, ensure that only the protein is displayed, without cofactors, waters, or ligands. If you want to map a particular site that is defined by a molecule, include that molecule in the Workspace along with the protein.
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Open the SiteMap panel.
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Select the task in the Specify task section. If you want to evaluate a single region, you must also select a molecule or entry to be used to define the region to be evaluated. The atoms of this molecule or entry must not be part of the protein.
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Make any settings in the Settings section to define the sites and the output.
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Choose Job Settings from the Settings button menu
set the job parameters in the Job Settings dialog box, and click Run to run the job.
When the job is finished, the site points and site maps are incorporated and displayed in the Workspace. The sites are returned in order of SiteScore, and each site is incorporated as a separate entry in the Project Table. The Surface Manager Panel is also opened so that you can manage the display of the site maps.The accptr, donor, and phob maps are displayed by default; the phil and surf maps are not displayed by default. Examples of site maps are shown in Sample Site Maps.
The default appearance of the six map types is as follows:
- Hydrophobic map—yellow mesh
- Hydrophilic map—green mesh
- Hydrogen-bond donor map—blue mesh
- Hydrogen-bond acceptor map—red mesh
- Metal-binding map—pink mesh
- Surface map—gray surface, 50% transparency
Thus, a red ligand oxygen atom that accepts a hydrogen bond from the receptor or coordinates with a metal center should appear in a red acceptor or pink metal-binding region, and a polar hydrogen on a blue amide nitrogen should appear in a blue donor region. (Red and blue are the default colors for oxygen and nitrogen.)
You can change the cropping of any of the maps with the following procedure:
- Select the map in the table.
- Click Limit.
- In the Limit dialog box, select Molecules from the Pick menu.
- Pick a site point.
- Enter the new distance from the site that the map will be cropped in the Distance text box.
- Click OK.
You can change the value at which the maps are contoured (the isovalue), as follows:
- Display the desired map, and undisplay all the others.
- Adjust the Isovalue slider, or enter a value in the adjacent text box.
The other display properties of these surfaces, such as color or representation can also be changed. For more information, see Surface Manager Panel.
Note: Do not change the molecular representation. Changing representations affects the display of the site points, and cannot be reversed without restarting Maestro.
If you want to examine the site maps separately, you can tile the Workspace by surface. See Tiling the Workspace for more information.
If you import the results of a SiteMap job using the Import Dialog Box, ensure that you select the option Import associated data files.
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.
SiteMap Panel Features
Task Section
In this section you can choose whether to examine the entire protein for potential binding sites, or restrict the search to a given region.
- Identify top-ranked potential receptor binding sites option
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Identify potential binding sites on the surface of the receptor, rank them and return the top-ranking sites. The atoms in the Workspace are taken to be the receptor, so you should ensure that only the receptor is displayed—no ligand, waters, or cofactors. This is the default option.
- Evaluate a single binding site region option
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This option allows you to evaluate the region of the receptor that is within a specified distance of selected non-receptor atoms, such as a ligand.
- Region about selected atoms plus N Å buffer will be examined text box
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Set the distance from the selected non-receptor atoms that is used to evaluate the binding site.
- Select non-receptor atoms defining region to evaluate picking tools
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Select the non-receptor atoms that you want to use to define the binding site region in conjunction with the cutoff, using the standard picking tools. The Pick menu allows you to pick an entry or a molecule. You must have only the receptor and the picked structure in the Workspace, as everything that is not the picked structure is taken to be the receptor.
If you want to include more than one molecule in the region for mapping (for example, a ligand and a cofactor), you should create an entry that includes only the molecules you want to use, and another entry for the receptor. You can then display both entries, and pick the entry that contains the two molecules to define the region.
Settings Section
This section provides basic controls for the site search and display of the site maps.
- Require at least n site points per reported site text box
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Set the minimum number of site point required in the initial site-finding stage to define a site. The default value is 15 site points; with this setting the average number in examined sites that bind ligands tightly is 150. This minimum applies to the second and subsequent sites; SiteMap always reports at least one site that contains the minimum number of points required to recognize a site, which is 3.
This setting is not relevant when you select Evaluate a single binding site region. However, SiteMap could find more than a single site even in this case if the region is large or contains subsites that SiteMap is unable to combine into a single site.
- Report up to n sites text box
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Specify the number of sites to report in the output. Sites are ordered by the number of points they contain. The default is 5 sites. This option is not available if Evaluate a single binding site region is selected.
- Use definition of hydrophobicity option menu
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Choose from more restrictive and less restrictive. The more restrictive option excludes points that border on too many assigned philic points, that have too few neighbors that are classified as phobic or inside the protein, or that border on too many points that occupy free space. In addition, regions that are exposed to solvent are assigned reduced hydrophobicity.1 The less restrictive option includes all points that are initially classified as phobic and does not apply these exclusions and modifications.
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See SiteMap Hydrophobic Map for more information.
- Use type grid option menu
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Set the size of the grid to use in computing the displayed site maps. The choices of coarse, standard, and fine correspond to grid spacings of 1.0 Å, 0.7 Å, and 0.35 Å.
This choice has no effect on the grids used for locating and analyzing sites, which always position the site points on a 1 Å grid.
- Crop SiteMaps at d Å from nearest site point text box
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The default distance from the nearest site point at which to crop the individual site maps for display. The default choice is 4 Å. This option does not affect the data, only the display. A different value can be specified later in the Surface Manager Panel.
- Detect shallow binding sites option
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Detect shallow binding sites suitable for protein-protein interactions, by decreasing the amount of enclosure and the threshold for van der Waals interactions (setting
-enclosureand-maxvdwcommand options to 0.4 and 0.55). - Attempt to subdivide sites larger than option and text box
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If a job generates sites with volumes larger than the volume specified in the text box, run a second job in a "compact" mode with tighter cutoff thresholds for determining groupings. Entries from the second job start with "
compact_site". This mode is helpful for avoiding pocket leakage and unnecessary union of sub-pockets.
Job toolbar
Manage job submission and settings. See Job Toolbar for a description of this toolbar.
The Job Settings button opens the SiteMap - 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.
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.