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Ligand/Solvent Placement Panel |
This panel allows you to place a ligand or solvent molecules in a region that contains an appropriate amount of density, and run a job to optimize the placement.
To open the Ligand/Solvent Placement panel, you can:
Click Ligand/Solvent Placement in the PrimeX panel.
Ligand and solvent molecule placement works by docking the molecules to a region of electron density, to optimize the placement. These regions are identified by analyzing a difference density map, which must be generated and displayed before you start. The density blobs (multiple connected density peaks) are listed in a table. You can then select the density blob you want to fit and the molecules or ligands, and run the job. You can only place multiple molecules in a single job. Each docked molecule with the protein included is returned as a separate entry.
To place a ligand or solvent molecule:
Generate a difference density map, and display it in the Workspace.
Open the Ligand/Solvent Placement panel.
If you do not have a difference density map displayed when you open the panel, you must generate one, then reopen the panel with the map displayed.
Select the source of the ligand or solvent molecule, under Use ligands from, and ensure that you have the desired file, Project Table selection, or solvent molecule selection.
You can place multiple molecules in a single run; the results for each will be returned as separate entries.
Select the density blobs you want to fit the selected molecule to.
You can select the blobs in the Density blobs table or by clicking on the blobs in the Workspace.
Set options as desired.
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 finishes, it is useful to perform a rigid-body refinement on the molecule to fine-tune the placement. You can do this in the Reciprocal-space Refinement panel.
After placing one set of molecules in a density blob, you can use the results to generate new difference maps and place other molecules in other blobs.
These three options allow you to choose different sources for the ligands to be placed. You can specify multiple ligands under each option, which allows you to determine which of several possibilites fits best at the given location. The options are:
Use ligands from a specified file. When you choose this option, the File name text box and Browse button become available. You can then enter the file name in the text box, or click Browse to navigate to the file in a file chooser.
Use the entries that are selected in the Project Table.
Use the solvent molecules that are selected in the table below. The table columns display the name, PDB ID, and number of atoms in the molecule. You can select multiple rows with shift-click and control-click.
Select this option to generate crystal mates near the active site. This option is useful if there are symmetry-related atoms that are part of another protein monomer that are close to the active site, and could influence the ligand placement. These symmetry-related atoms are then included in the grid generation for the Glide docking job.
Select this option to run LigPrep on the ligand before placing it. The LigPrep job is run as the first part of the ligand placement job. You must have a LigPrep license to use this option. For more information on LigPrep, see the LigPrep Panel topic or the LigPrep User Manual.
Select this option to run a post-docking minimization of the ligand in the field of the receptor. This option improves the geometry of the docked ligand.
Enter the weights to be given to the energy and scoring terms in the ligand placement job. The two weights are:
Energy—Weight of density terms used to mix into the Coulomb/van der Waals energy. Default:120.
Score—Weight of density terms used in the rough scoring function. Default: 50.
The allowed values for both weights range from 1 to 9999.
This button opens the Calculation Settings dialog box, in which you can set the resolution limit, overall B-factor scaling, choose a bulk solvent correction, set limits for rejecting reflections, and choose whether to include hydrogen atoms in the output.
Table of density blobs computed from the peaks in the current difference map. The blobs are listed in order of volume, which is displayed in the table. You can select only one blob at a time. The selected blob is used for placement of the ligand or solvent molecule. When you select a blob in the table, the Workspace view centers on the blob, and the sphere that marks the blob is colored red.
Recompute the density blobs from the map and update the table. This button is useful if you generate a difference density map after opening the panel, for example, or make changes in the Workspace.
Select the next blob in the table or the previous blob.
The value in this text box sets the cutoff for the volume of the blobs that are displayed in the Density blobs table. Blobs with volumes smaller than the value set are not displayed.
Select this option to pick density blobs in the Workspace. When a blob is picked, it is colored red, and is also selected in the Density blobs table.
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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