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 this panel: click the Tasks button and browse to Lead Optimization → MM-GBSA.
To open this panel from the entry group for the results of a Glide docking job, and load the results, use the Workflow Action Menu .

  • Using
  • Features
  • Additional Resources

Using the Prime MM-GBSA Panel

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 Workflow Panel, and an implicit membrane model added if needed. After preparing your structures, set up and run the job. See Prime MM-GBSA for instructions.

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. For information on command usage and options, see prime_mmgbsa Command Help and prime_mmgbsa—Calculate Ligand Binding Energies.

Prime MM-GBSA Panel Features

Structures section

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

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

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.

Options section

This section provides settings that control some details of the calculations performed.

Solvation model option menu

Choose a continuum solvation model for the refinement. The choices are:

  • VSGB—Use the variable-dielectric generalized Born model, which incorporates residue-dependent effects. The solvent is water.
  • Vacuum—Do not include solvation.
  • Chloroform—Use chloroform as the solvent, modeled with the Surface Generalized Born (SGB) method.
Force field option menu

Choose the force field for the current task. The choices are OPLS_2005 and OPLS4. The default is OPLS4 if it is available, otherwise it is OPLS_2005, unless you set the default in the Force Field settings section of the Preferences Panel.

Use customized version option

Use your customized version of the OPLS4 force field, rather than the standard version in the distribution. Only available when you choose OPLS4 from the Force field option menu and you have the appropriate license. This option is set by default to the value of the Use custom parameters by default option in the Preferences panel, under Jobs - Force field, when the current panel is opened. The default directory for the customized version can also be specified as a preference, in the same location.

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

Select the set of custom parameters for the OPLS4 force field. Opens the Set Custom Parameters Location Dialog Box. Only available when you choose OPLS4 from the Force field option menu and you have the appropriate license.

Use ligand input partial charges option

If the ligand structure source has partial charges for the ligands, such as those from QSite, use these partial charges instead of those generated by the force field.

Use implicit membrane option

Use an implicit membrane model for the calculations. The membrane must be set up beforehand: you can do this from any of the Prime Refinement panels, using the Prime Membrane Setup Panel.

Protein flexibility section

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

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. 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.

If you want to add or exclude residues, choose also add (logical OR), exclude (logical AND NOT), or intersect with (logical AND) and specify the residues with the picking tools below this option.

Picking tools for adjusting flexible region

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

Choose the method that is used to treat the flexible residues.

  • Minimize—Minimize all atoms in each residue.
  • Minimize side chains only—Minimize only the side chains in each residue, leaving the backbone fixed.
  • Minimize polar hydrogens only—Minimize only the hydrogens attached to electronegative atoms, leaving all other atoms in each residue fixed.
  • Hierarchical Sampling—Systematically sample ligand positions, orientations, and conformations along with receptor residues.
Use constraints on flexible residues option

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.

Job toolbar

Manage job submission and settings. See Job Toolbar for a description of this toolbar.

The Job Settings button opens the Prime MM-GBSA - Job Settings Dialog Box, where you can make settings for running the job.

Status bar

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. You can also reset the panel from the Job toolbar.

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.

Tutorials

Related Topics