WaterMap - Perform Calculation Panel
In this panel you can set up and run a WaterMap simulation, which uses Desmond to run a molecular dynamics simulation of water molecules in the ligand binding site of a receptor.To improve sampling, a standard GCMC code forms part of the default algorithm which attempts to take care of the exchange of water molecules in deeply buried pockets. The receptor is restrained during the simulation. The excess enthalpy and entropy, and thus the free energy, of the water sites is estimated. These quantities can be used as a guide to which water molecules could be advantageously displaced on ligand binding.
WaterMap simulations can include metal atoms that are bonded to the protein via one or more zero-order bonds. Water molecules that have zero-order bonds to the metal are retained as chelated solvent during the simulation.
To open this panel, click the Tasks button and browse to Lead Optimization → Perform Calculation.
- Using
- Features
- Additional Resources
Using the WaterMap - Perform Calculation Panel
To set up a WaterMap simulation:
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Import the receptor or the receptor-ligand complex into Maestro.
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Open the WaterMap - Perform Calculation panel.
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Select Ligand or Residues for the definition of the binding site.
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If you selected Ligand, select Pick and pick a ligand atom in the Workspace. If you want to include the ligand in the simulation, select Retain ligand.
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If you selected Residues, click Select and select the residues that define the binding site.
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(Optional) Enter a distance for the analysis of waters. The distance is calculated from the ligand or from the selected receptor residues, depending on the option selected for defining the binding site.
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If you want to truncate the protein beyond the analyzed waters, select Truncate protein.
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If you have existing waters, choose an option for treating them from the Treatment of existing waters option menu.
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Enter the simulation time in the Simulation time text box.
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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.As WaterMap runs Desmond, the job must be run on a GPU host. A typical WaterMap job takes about 1.5 hours on a GPU.
When the job finishes, the results are incorporated into the project.
You can also run the WaterMap calculation from the command line. Once you have set the up the simulation parameters, click Write to write out the input files needed to run a WaterMap job from the command line. This button opens a panel that requests a job name. After entering the job name, click Write. The following files are written out:
jobname.msj — the multisim input file.
jobname.csb — the system builder input file.
jobname-solute.mae — the truncated protein.
jobname-ligand.mae — the ligand.
jobname-protein.mae — the whole protein.
A typical command for running WaterMap might look like:
$SCHRODINGER/watermap -JOBNAME protein7c -HOST my_gpu_host \ -i protein7c-solute.mae -m protein7c.msj
This command runs a WaterMap job "protein7c" on a host "my_gpu_host". See watermap Command Help for more information on the command-line options.
WaterMap - Perform Calculation Panel Features
In this section, you define the binding site, either by specifying the ligand or the receptor residues. The receptor and ligand must be displayed in the Workspace. There are two options for defining the site, and an option for waters to consider.
- Ligand option
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Select this option to define the binding site in terms of the ligand. You can then select Pick and pick a ligand atom in the Workspace to identify the ligand. The selected ligand molecule is highlighted with yellow markers. If you pick the wrong molecule, you can pick again to select the correct molecule. If you want to include multiple ligands, you can use shift-click to add a ligand to the selection.
If you want to include the ligand in the simulation as well as the protein, select Retain ligand. This is useful if you want to compare the water map for the holo protein with that from the apo protein.
- Residues option
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Select this option to define the binding site by selecting residues. Click Select to open the Atom Selection dialog box and select the residues. When you click OK, the ASL expression for the residues is entered in the text box.
- Analyze waters within N Å of selected atoms text box
- Specify the distance from the binding site residues for which waters will be analyzed. The default of 10 Å roughly equates to 3 hydration shells, where a typical H-bond is between 2.5 and 3.5 Å. It is rare to see effects spanning further than three levels of hydration and so the distance would be very unlikely to need extending.
In this section you set up the simulation parameters.
- Truncate protein option
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Truncate the protein at a distance that includes the region 10 Å beyond the waters that you included in the analysis. The effect is to truncate the protein at a distance of 10+N Å from the residues used to define the binding site, where N is the number entered above for analyzing the waters. All residues with at least one heavy atom within the truncation distance from any heavy atom in the ligand are retained. Broken bonds are reformed and capped with hydrogen atoms. This option is selected by default.
Truncating the protein often has little effect on the results yet speeds up the calculation. However, it is recommended to only consider truncation if working with a very large system and time is a concern, and allostery is not thought to play a significant role in the ligand binding.
- Force field option menu
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Choose the force field for the simulation.
For WaterMap, only OPLS4 is available.
- Use customized version option
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Use your customized version of the OPLS4 force field, rather than the standard version in the distribution.
If the customized version is missing or invalid, the text of this option turns orange and an orange warning icon is displayed to the right, with a tooltip about the problem.
- Parameter set button
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Select the set of custom parameters for the OPLS4 force field. Opens the Set Custom Parameters Location Dialog Box.
- Treatment of existing waters option menu
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From this option menu you can decide how to treat water molecules that are included with the protein structure. Water molecules that have a zero-order bond to a metal are considered to be part of the receptor, and are retained. The options are:
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as solvent—Treat the water molecules as part of the explicit solvent. These water molecules will be included in the analysis.
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as solute—Treat the water molecules as part of the solute. These water molecules will not be included in the analysis.
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delete—Delete the existing water molecules before starting the simulation.
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- Simulation time text box
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Enter the desired length of the simulation in ns in this text box. The simulation time is 2.0 ns by default, and should not be set less than 1.5 ns.
- Do not return trajectory upon job completion option
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If this option is selected, the trajectory will not be copied back to the working directory when the job finishes, but is discarded. The default is to copy the trajectory.
Manage job submission and settings. See Job Toolbar for a description of this toolbar.
The Job Settings button opens the WaterMap - Perform Calculation - 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.