WaterMap - Examine Results Panel

WaterMap - Examine Results Panel Features

• Load Results buttons
• Adjust the view when analyzing option
• Display options
• Site label option menu
• Color sites by option menu
• Color scale options
• Show color in table option
• Water sites table
• Pick to select sites option
• Show only water sites with section
• Score ligands button
• Create properties for individual sites option
• Score only selected sites option
• Perform WM/MM Scoring button
• Import Trajectory button
• Import Water Frames button
• Archive button
• Export to LiveDesign button
• Open Ligand Interaction Diagram button
• Reset button

Load results buttons

These buttons allow you to choose the source of the results that are analyzed and displayed.

• Import Files—Click this button to open a file selector and navigate to the WaterMap output files. WaterMap output file names end with one of following extensions: _wm.mae, _wm.maegz, or _wm.mae.gz. You can also import results from WaterMap archive files, _wm.zip or _wm.tgz. The WaterMap output file includes one entry for WaterMap water site data, one for the receptor and one for the ligand. These entries are read in as an entry group in the Project Table.

  You can select multiple files to import.

• Analyze Workspace—Analyzes the water sites for the entries that are included in the Workspace. This can be used to switch between water maps. Before clicking Analyze Workspace, make sure to include in the Workspace the WaterMap site and receptor entries. You can include another ligand in the Workspace for analysis, or modify the existing ligand (it is advisable to duplicate the existing ligand entry before modifying it), then click this button to obtain results for the new structure. You can include multiple WaterMap results in the Workspace for simultaneous analysis.

Adjust the view when analyzing option

When analyzing the Workspace, adjust the view so that the binding site fills the Workspace. You might want to disable this option if you have already optimized the view manually.

Display options

These options control what is shown in the Workspace.

• Receptor—Display the receptor atoms for all residues that have atoms within 5 Å of the water sites.
• Ligand—Display the ligand in the Workspace.
• H-bonds—Show H-bonds between the displayed receptor atoms and ligand atoms the Workspace.
• Markers—Show markers for the water sites that meet the enthalpy and entropy cutoff values. The spheres are semitransparent: brighter cyan spheres have lower (more negative) enthalpy (i.e., more enthalpically stable); brighter yellow spheres are more entropically stable (i.e., lower or more negative values of -TdS). The marker style depends on the Shape by entry option.
• Shape by entry—Display the water sites with shapes that depend on the entry to which the site belongs. Five shapes are used: sphere, cube, tetrahedron, octahedron, dodecahedron. If more than five water maps are displayed simultaneously, this list is reused. This option is selected by default for multiple water maps, so that you can identify which entry the site belongs to.
• Dipoles—Display the average dipole moment of the water at each site as an arrow. The arrow can be configured in the Workspace - Dipole moment tab of the Preferences panel.
• Waters—Display water molecules for each selected site. The display is a sample of the water molecules that contribute to the site. This option is useful to show whether the waters prefer a particular orientation in the site.
• Ligand surface—Display a molecular surface for the ligand.
• Water density—Display a surface that represents a particular value (isovalue) of the average water density. The isovalue can be changed in the Surface Manager Panel. The density of bulk water is 0.033 molecules/ų; this is the default isovalue.
• Cavity map—Display a surface for regions that do not contain any atoms: no protein, no ligand, no waters. The surface isovalue is the probability that a sphere of radius 1 Å does not overlap with any other atom; the default value is 0.4. If multiple WaterMap results are displayed, the surfaces are colored with the Color by Entry color scheme. These are essentially de-wetted regions and hence are highly unfavorable for water. Filling cavities with hydrophobic groups such as CF₃ that do not need to be solvated can increase the binding energy substantially.
• Free energy density—Display a surface that represents a particular absolute value (isovalue) of the free-energy density of the water. The surfaces that enclose higher positive values of the free-energy density are colored red, and indicate unfavorable regions. The surfaces that enclose lower negative values of the free-energy density are colored green, and indicate favorable regions. The surface isovalue is 0.033 kcal mol⁻¹Å^-3, and can be changed in the Surface Manager Panel. This is also called a "continuous water map", as it shows the shape of the hydration site more accurately than the spheres. The shape may be important for selecting R-groups to efficiently displace a water from a given site. For multiple water maps, changing the surface style (e.g. using solid or mesh surfaces) can help in comparing the hydration sites.

Site label option menu

Label the sites with the values of the property chosen from this option menu.

Color sites by option menu

Choose a scheme for coloring the water sites by the thermodynamic properties of the site. The schemes are as follows:

• ΔG (simple)—green for more negative values, red for more positive values.

• ΔH and -TΔS—Brighter cyan for lower enthalpy, brighter yellow for lower entropy. Both are applied, so brighter green has lower enthalpy and entropy.

• Entry—Color all sites from the same entry with the same color, using the Maestro Color by Entry color scheme.

Color scale options

Select Relative or Absolute to control whether the colors are mapped to a relative scale for the property or to an absolute scale. For the absolute scale, the color ramp is applied for values between -5 and +5 kcal mol⁻¹; values outside this range are colored with the end value. Using an absolute scale is useful when there is an outlier site, because the outlier has the effect of reducing the color differences between the other sites.

Show color in table option

Color the table rows by the site color.

Water sites table

This table displays the results of the WaterMap simulation as a set of sites. Clicking a column header sorts rows in ascending or descending order of the data in the column. You can select a row either by clicking it or by selecting Pick to select site and picking a site in the Workspace. You can select all rows in the table by clicking Select All. Sites that are selected are drawn with a larger radius than the unselected sites.

You can export all the table data to a CSV file by clicking Export to CSV. This button opens a file selector in which you can navigate to a location and name the file.

The table columns are as follows:

Site		Site index.
Entry ID		Entry ID for the site. Present only when multiple maps are displayed, to identify the entry for each site.
Occupancy		Average occupancy of the water site by water molecules. The values range from 0 (water molecules are never found in the water site) to 1 (water molecules occupy the site for the entire time of the simulation).
Overlap		Fractional overlap of water site with ligand. A value of 1 means that the water molecule would be displaced by the ligand.
ΔH		Average interaction enthalpy between the water molecule that occupies the site and the rest of the system relative to bulk water. Sites with positive ΔH values correspond to waters that are enthalpically less stable in the protein binding site than in bulk water while negative values correspond to waters that are enthalpically more stable in the protein binding site than in bulk water.
-TΔS		Excess entropy of the water molecules associated with the water site compared to that of bulk water molecules. Water molecules in the the binding site of the protein generally have lower entropies than in bulk water and thus have postive -TΔS values. Larger values correspond to water molecules that have more significant entropic penalties and thus tend to be less stable in the binding site.
ΔG		Average interaction free energy between the water molecule that occupies the site and the rest of the system relative to bulk water.
#HB(WW)		Average number of hydrogen bonds formed between the water molecule that occupies the site and other water molecules.
#HB(PW)		Average number of hydrogen bonds formed between the water molecule that occupies the site and the protein.
#HB(LW)		Average number of hydrogen bonds formed between the water molecule that occupies the site and the ligand.

Pick to select sites option

Select this option to pick sites in the Workspace. Click selects a single site and deselects all others, shift-click adds sites to the selection, and control-click selects or deselects an individual site without affecting the selection of other sites.

Show only water sites with section

In this section you can limit the sites listed in the table to those that meet specified conditions on one or more selected properties. The properties you can select are: Enthalpy (ΔH), Entropy (-TΔS), Free Energy (ΔG), and Overlap factor. When you select or deselect an option, the table is updated.

Each of these options has a slider and text boxes, to define the range of the property that is used to select the sites shown in the table. Sites with the property within the range are displayed, sites with the property outside the range are not displayed. You can invert this range so that sites outside the range are displayed and sites inside are not displayed, by selecting Invert range.It is often useful to invert the range to exclude sites that have a free energy close to zero. This eliminates sites from the display whose displacement has little effect on binding, leaving the more interesting sites that are more stable or more unstable.

You can also display hydration sites within a specified distance of an atom selection, by selecting Distance, and providing an ASL expression in the text box, or clicking Select and using the Atom Selection Dialog Box to select the atoms.

Score Ligands button

With this button you can calculate relative thermodynamic properties (enthalpy, entropy, and free energy) for the selected ligands in the Project Table. You must also have the WaterMap results included in the Workspace. The calculated difference in the binding free energy between two ligands is the difference in the WM ligand deltaG property for the two ligands.

It is important that the ligands be properly positioned in the binding site and that energetic comparisons be restricted to similar ligands. Since WaterMap is designed to identify differences in binding free energies resulting solely from displacement of water molecules, it is also important that the differences in the ligand structures do not result in different interaction energies with the protein. One highly recommended approach is to compare ligands that are built from a common pre-positioned scaffold. For example, if one ligand has a fluorine in place of a hydrogen in the other ligand, it is recommended that you duplicate one of the ligands in the Project Table to create a copy of the ligand and then use the Build toolbox to either replace the F with an H or the H with an F, depending on which ligand was duplicated. The two ligands are then identical for the purpose of scoring, but have different poses.

Create properties for selected sites option

If you select this option, energy contributions from the selected water sites are added to the selected ligand entries in the Project Table when you click Score Ligands.

Score only selected sites option

When scoring ligands, calculate the score using only the selected sites, rather than all sites.

Perform WM/MM Scoring button

Open the WM/MM Scoring Panel, to run a calculation to evaluate binding energy terms, using Prime MM-GBSA. In this panel you can select the WaterMap structures from the Workspace or from a file, and the ligand structures from the selected entries in the Project Table or a file. You can also specify the region of the protein that is treated flexibly, and then run the job.

Import Trajectory button

Import the trajectory for the WaterMap run into the Project Table. You can then view the trajectory by clicking the T button in the Title column of the Entry List or Project Table.

Import Water Frames button

Import the trajectory frames for the water molecules into the project. The frames can be displayed from the Project Table to view the location of the water molecules, and played through with the ePlayer.

Archive button

Archive the WaterMap results for the entry that is currently displayed in the panel, in a _wm.zip file.

Export to LiveDesign button

Export the selected water sites to LiveDesign. You should set up the water sites as you want them to appear when you use them from LiveDesign, including any coloring settings, etc. Only the selected sites are exported. If you are not connected to LiveDesign, a dialog box requesting your credentials is opened, then the Export Watermap Model to LiveDesign dialog box opens, in which you can specify the model name, folder, and description for the water sites. The currently connected LiveDesign host information will appear in the status bar at the bottom of the panel. If there is no connection, the status will state: "Disconnected from LiveDesign."

Open Ligand Interaction Diagram button

Open the Ligand Interaction Diagram Panel to display a 2D rendering of the interaction of the Workspace ligand with the receptor, waters, and cofactors.

Reset Panel button

Clears the Water sites table. To redisplay the sites, you must click Analyze Workspace.

Related Topics

• WaterMap - Perform Calculation Panel
• Project Table Panel
• The ePlayer
• Ligand Designer Panel