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Prime MM-GBSA Panel |
This panel can be used to calculate ligand binding energies and ligand strain energies for a set of ligands and a single receptor, using the MM-GBSA technology available with Prime.
To open the Prime MM-GBSA panel, you can:
Choose Tasks → Binding Energy Estimation → MM-GBSA in the main window.
Choose Applications → Prime → MM-GBSA in the main window.
The purpose of this panel is to facilitate calculations of ligand binding energies and ligand strain energies, using Prime technology. The ligands and the receptor must be properly prepared beforehand, for example, by using LigPrep and the Protein Preparation Wizard.
After preparing your structures, you can set up the calculation as follows:
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.
(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.
If you want to use the Prime implicit membrane model, select Use implicit membrane. The receptor you choose must have been already set up with the membrane, using the Prime Membrane Setup Panel.
(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.
(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.
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; or choose Write to write the input file and run the job from the command line.
When you set up the job in the Start 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.
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.
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.
Specify the source of the ligands and the receptor separately. For the ligands, select either Selected entries in Project Table or File. For the receptor, 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.
Choose a continuum solvation model for the refinement. The choices are:
If the ligand structure source has partial charges for the ligands, use these partial charges instead of those generated by the force field.
Use an implicit membrane model for the calculations. The membrane must be set up beforehand: you can do this from the options dialog box in any of the Prime Refinement panels.
This section allows you to define flexible residues in the protein and how they are treated. The distances are defined using all ligands processed.
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.
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:
Choose the method that is used to treat the flexible residues.
Place harmonic constraints of 1.0 kcal mol−1 Å−2 on the flexible residues, so that they do not deviate too much from their initial position. The non-flexible residues are frozen.
The Job toolbar is used to make settings for a job and to start it.
Enter a name for the job in this text box.
This button opens the Job Settings dialog box. The arrow to the right opens a menu, from which you can make settings or perform actions that are related to the job.
The menu items are described below.
This icon indicates when there are jobs running for the application that belong to the current project. It starts spinning when the first job starts, and stops when there are no more jobs running. If a job fails to start, it changes to an exclamation point.
Clicking the button shows a small job status window that lists the job name and status for all active jobs submitted from the current panel (for Jaguar and MacroModel this means all jobs from any of the application panels). You can double-click on a row to open the Monitor panel and monitor the job, or click the Monitor button to open the Monitor panel and close the job status window. The job status is updated while the window is open. If a job finishes while the window is open, the job remains displayed but with the new status. The rows are colored according to the status: yellow for submitted, green for launched, running, or finished, red for incorporated, died, or killed. Click anywhere outside the window to close it.
Run the job with the current job settings.
The status bar displays information about the current job settings for the panel. This includes the job name, task name and task settings (if any), number of subjobs (if any) and the host name and job incorporation setting. It also displays a message for a short time when you start a new job.
The status bar also contains the Help button, which opens the help topic for the panel.
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