VSW - Receptor Constraints Dialog Box

In this dialog box you can select receptor-based constraints, and specify a ligand core constraint, for Virtual Screening Workflow jobs.

To open this dialog box, click Constraints in the VSW - Receptor dialog box.

  • Using
  • Features
  • Additional Resources

Using the Receptor Constraints Dialog Box

To set up an H-bond or metal constraint for a new grid:

  1. Select Pick atom to add H-bond or metal constraint.

  2. Pick the receptor atom for the constraint in the Workspace.

The constraint is added to the table and marked in the Workspace. The type of constraint is determined from the type of the atom that you picked.

To set up a positional or NOE constraint for a new grid:

  1. Click New Positional/NOE.

  2. Use the picking controls in the New Position dialog box to pick the receptor atoms that define the constraint center.

     

  3. Change the name from the default, if desired.

  4. Enter a maximum radius for the constraint.

  5. If defining an NOE constraint, enter a minimum radius.

  6. Click OK.

The constraint is added to the table, with the appropriate type. You must also define a ligand feature for the constraint. See Receptor Grid Generation Panel for more information.

To define a ligand feature that must match a positional or NOE constraint:

  1. Select the constraint in the table.

  2. Click Feature to open the Edit Feature dialog box.

  3. Click New to open the Edit Feature Pattern dialog box.

  4. Enter a SMARTS pattern in the SMARTS pattern text box, or click Get from Selection to create a SMARTS pattern from the selected atoms in the Workspace.

  5. Enter the atom numbers of the atoms in the SMARTS pattern that you want to match the constraint, and click OK.

  6. If you want to add more patterns, click New in the Edit Feature dialog box again, and repeat the above two steps to define the pattern. Patterns are matched in the order given in the pattern list.

  7. If you want to exclude a particular pattern from matching the constraint, select the check box in the Exclude column. Excluded patterns are processed before other patterns.

  8. Click OK.

The feature is added to the constraints table. You can edit the feature to add, edit, or delete patterns by selecting the constraint and clicking Feature. Features can be defined for both new and existing grids. See Ligand Docking Panel DEPRECATED for more information (but note also that there are differences between VSW and Glide).

To delete a constraint for a new grid:

  1. Select the constraint in the table.

  2. Click Remove.

To request use of constraints in docking:

  1. Select the desired constraints in the Use column of the table.

  2. Select a Must match option.

  3. If you selected At least, enter the number of constraints that must be met in the text box.

To restrict the ligand core to a reference position:

  1. Select Restrict ligand core to reference position.

  2. Enter a tolerance for the RMSD of the ligand from the reference position in the Tolerance text box.

  3. Select Pick core-containing molecule, and pick a ligand atom.

    You must have the receptor and ligand displayed to pick the ligand atom.

  4. Choose an option to define the core atoms in the ligand.

    The choices are All (all atoms in the ligand), All heavy (all nonhydrogen atoms in the ligand), and SMARTS.

    If you chose SMARTS, enter the SMARTS pattern in the text box, or select the desired core atoms in the Workspace, and click Get from selection.

  5. If you want only the ligands that match the core pattern to be docked, select Skip ligands that do not match core pattern.

Receptor Constraints Dialog Box Features

 

Constraints table

This table lists the constraints that are available for use in the docking job. If you are using a pregenerated grid, the constraints defined with the grid are listed in the table. If you are generating a grid, the table is initially empty and you can pick atoms to define H-bond or metal constraints. The table columns are described below.

Use Check box to select the constraint for use in docking. Click to select or deselect.
Constraint Name Name of the constraint. For pregenerated grids, this is the name used when the grid was generated. For new grids, the name is assigned and cannot be changed.
Type Type of receptor constraint. Hydrogen bond constraints are classified into H-bond for hydrogen-bond acceptors and Polar Hydrogen for hydrogen-bond donors (i.e. hydrogen atoms). Note that the minimum donor and acceptor angles (90 and 60 degrees) are smaller than those used by Maestro (120 and 90 degrees).
Atom Index of atom in the receptor that was used to define the constraint.
New Positional/NOE button

Define a new positional or NOE constraint. Opens the VSW - New Position dialog box, in which you can select atoms for the positional or NOE constraint, specify a name and a radius, and for NOE constraints specify a minimum radius.

Remove button

Select a row in the constraints table and click this button to remove the constraint. This button is only available if you are generating a grid.

Feature button

Edit the feature definition for the positional or NOE constraint that is selected in the constraints table. Opens the VSW - Edit Feature dialog box. In this dialog box you can construct a feature as a combination of SMARTS patterns, by adding patterns with the New button. For each pattern, you can define the atoms in the pattern that must match (the SMARTS indices). Patterns can be excluded, so that the feature does not include matches to these patterns.

Pick atom option

Select this option to pick an atom in the Workspace to define a hydrogen-bond or metal constraint. This option is only available if you are generating a grid.

Must match options

Select an option to specify how many of the constraints must be satisfied during docking. If you select All, then all constraints that are selected in the Use column must be satisfied. If you select At least, the number of constraints given in the text box must be satisfied. This number must be less than the number selected in the Use column.

Restrict ligand core to reference position option

Restrict the docking of ligands so that the ligand "core" lies within a given RMSD of the core in the reference ligand. The core is defined in terms of a set of atoms or a SMARTS pattern; if the ligand does not contain these atoms, it can be skipped.

Tolerance text box

Enter the tolerance for the RMSD in angstroms that is used to restrict the docking to the reference position.

Pick core-containing molecule option

This option allows you to pick the molecule that is used to define the reference position for the core constraint.

Core atoms options

There are several options for defining the core atoms:

  • Maximum common substructure—Use the maximum common substructure of the ligand and the core-containing molecule to define the core atoms.
  • All heavy atoms—Use all non-hydrogen atoms in the reference ligand as the core atoms.
  • All atoms—Use all atoms in the reference ligand as the core atoms.
  • SMARTS pattern—Define the core atoms in terms of a SMARTS pattern. You can pick atoms in the Workspace and click Get From Selection to define the SMARTS pattern, or you can type a SMARTS pattern into the text box. The atoms in the core-containing molecule that match the pattern are marked in the Workspace with green markers.
Skip ligands that do not match core pattern option

When this option is selected, if a ligand does not match the core pattern it will not be docked. This option is selected by default. If it is deselected, ligands that do not match are docked, but the RMSD with the core is not calculated.

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