WM/MM Scoring Panel
The WM/MM Scoring panel allows you to set up and run a job for estimation of the free energy of binding, using Prime MM-GBSA for the terms involving the internal energies, Coulomb and van der Waals interactions, ligand desolvation, and internal strain, and the WaterMap score for the water displacement terms.
To open this panel, click the Perform WM/MM Scoring button in the WaterMap - Examine Results Panel.
- Using
- Features
- Additional Resources
Using the WM/MM Scoring Panel
The panel can be used for scoring a congeneric series of ligands, in which the ligands do not induce any changes in the protein (side-chain flips, for example), there are no water-mediated hydrogen bonds, and there are no significant contributions from protein or ligand strain or conformational entropies to the relative binding free energy.
To prepare the system, you should use the full protein preparation work flow in the Protein Preparation Wizard, including the restrained minimization with the crystal lead in the active site. For the ligands, members of the congeneric series should be built by making peripheral additions to the core of this lead. The series should not change the charge on the ligand.
The job performs the Prime MM-GBSA calculation with the options set in the panel, and constructs the WM/MM score from the MM-GBSA results and the WaterMap results. You can distribute this job over multiple processors.
After preparing your structures, you can set up the calculation as follows:
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Specify the source of the structures.
You can take structures from a Pose Viewer file (Glide output), or from separated ligand and protein structures. If you choose the latter option, you must ensure that the ligands and the protein are properly prepared and aligned. The protein structures must be WaterMap structures, which you can take from a file or from the Workspace entry.
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(optional) Choose calculation settings.
If you want to use ligand partial charges evaluated by some other program, such as QSite, select Use ligand input partial charges. The input partial charges on the ligand will then be used instead of those assigned using the default force field.
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(optional) Specify a region within a certain distance of the ligand for which the protein structure will be relaxed in the calculation.
By default, all protein atoms are frozen, and only the ligand structure is relaxed. The larger the flexible region, the longer the calculation will take.
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(optional) Choose a sampling method for the flexible protein residues. The default is to minimize them. You can instead choose to minimize just the side chains, to allow them to move in response to the ligand; or to minimize just the polar hydrogens, to optimize them for hydrogen bonding. In addition, you can constrain the residues so that they do not move very much from their input position.
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Choose Job Settings from the Settings button menu,
set the job parameters in the Job Settings dialog box, then click Run in the dialog box to run the job; or choose Write to write the input file and run the job from the command line.
When you make settings in the Job Settings dialog box, you can set the number of CPUs and number of subjobs if you are running the job on a multiprocessor host or submitting it to a queuing system. The ligand set is divided between the specified number of subjobs.
If you want to start over, click Reset.
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.
If you want to run this job from the command line with the prime_mmgbsa command directly, you should use the -watermap option to specify the location of the WaterMap results (structure file).
WM/MM Scoring Panel Features
Specify the source of the ligands and the receptor. The ligands must be pre-positioned with respect to the receptor, and the receptor must be prepared as for a Prime refinement calculation. You should remove explicit waters and ions. If you read structures from a file, you can use uncompressed (.mae) or compressed (.maegz, .mae.gz) files.
- Take complexes from a Maestro Pose Viewer file option and controls
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If you want to use a pose viewer file for both the receptor and the ligands, select this option. To specify the file, enter the file name and path in the text box, or click Browse and navigate to the file.
- Take complexes from separated ligand and protein structures option and controls
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Specify the source of the ligands and the receptor separately. For the ligands, select either Selected entries in Project Table or File. For the WaterMap structures, select either Workspace entry or File. If you select File for either source, you can enter the file name and path in the text box, or click Browse and navigate to a file.
This section provides settings that control some details of the calculations performed.
This section allows you to define flexible residues in the protein and how they are treated. The distances are defined using all ligands processed.
- Distance from ligand (Å) text box and option menu
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Specify the distance from the first ligand within which protein residues are treated as flexible. Any protein residue with an atom that lies inside this distance is considered flexible.
If you want to add or exclude residues, choose also add (OR), exclude (AND NOT), or intersect (AND) with and specify the residues with the picking tools below this option.
- Picking tools for adjusting flexible region
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Use these picking tools to define the residues that are to be added or excluced, or that are used to limit the region around the ligand. Enter an ASL expression in the ASL text box, select Pick and pick atoms in the Workspace, or use one of the buttons to select the residues:
- All—include all residues
- Selection—use the Workspace selection. This requires the protein to be in the Workspace.
- Previous—Use the previous selection from the Atom Selection dialog box.
- Select—Open the Atom Selection dialog box to specify the residues.
- Sampling method option menu
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Choose the method that is used to treat the flexible residues. You can minimize the entire residue, minimize only the side chains, or minimize only the polar hydrogens.
- Use constraints on flexible residues option
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Place harmonic constraints on the flexible residues, so that they do not deviate too much from their initial position. The non-flexible residues are frozen.
Manage job submission and settings. See Job Toolbar for a description of this toolbar.
The Job Settings button opens the WM/MM Scoring - 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.