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Ligand Docking — Constraints Tab |
The Constraints tab of the Ligand Docking panel lists all the Glide constraints that are defined for the receptor grid files you specified in the Settings tab, and provides the means to selectively apply these constraints in docking.
The constraints can be set in groups, up to a maximum of four groups. Each group of constraints is applied to the ligand (a Boolean AND is applied between groups). Within each group, you can require all constraints to be satisfied, or you can set a minimum number of constraints in the group that must be satisfied. In this way you can define required or optional constraints within each group. Overall, there must be 4 or fewer required constraints, across all groups.
For example, suppose the grid contains a hydrogen bond constraint hbond1 and two positional constraints pos1 and pos2. If you want to enforce the hydrogen bond constraint, and require only one of the two positional constraints, you would click the Use check box for hbond1 in Group 1 and select All under Must match; and click the Use check boxes for pos1 and pos2 in Group 2, select At least under Must match, and enter 1 in the text box.
The definition of a constraint includes the ligand feature to which it matches. These features are defined in terms of SMARTS patterns. To edit the ligand feature definitions, select the table row for the constraint and click Edit Feature. The Edit Feature dialog box opens, allowing you to select the feature type; import or export feature sets; and add, edit or delete patterns.
To use a different combination of the available constraints, run another docking job and select the desired constraints.
Glide constraints can be used only in flexible docking jobs. (Ensure that Dock flexibly is selected in the Settings Tab.) Glide constraints can be used in HTVS mode, but may result in poor pose recovery.
Note: If you include positional constraints, you must define the ligand feature that it should match. No default feature definition is provided, and the job cannot be run until the feature is defined. To define the ligand feature, select the appropriate row in the Available constraints table and click Edit Feature. The feature can then be defined in the Edit Feature dialog box.
The Constraints tab contains four subtabs for defining constraint groups. Each subtab has the same structure.
This option is selected by default. When the receptor is displayed, atoms for which H-bond/metal constraints are defined are marked with a red asterisk and padlock. Positional and NOE constraints are marked with gray translucent spheres. When a constraint is selected, the padlock and asterisk turns blue, and the cells or spheres are colored red. To undisplay the markers, deselect this option.
The constraints are presented in four tabs, labeled Group 1 through Group 4. The number in parentheses after the group name is the number of constraints that must be satisfied in this group, and reflects the minimum number of constraints used. This value depends on the selection made under Must match.
Each group has the full range of constraints available. You can select the same constraint in two groups.
This table lists the constraints that are available for use in the docking job, and provides the means to select constraints for use. You can select a single row in the table for various actions on the constraint. The table columns are described below.
Check box to select the constraint for use in docking. Click to select or deselect.
Constraint name. This is the name defined in the Constraints tab of the Receptor Grid Generation panel.
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).
Name of the feature type in the ligand that must match the constraint. The available feature types are: Acceptor, Charged Acceptor, Neutral Acceptor, Acceptor Including Halogens, Donor, Donor Including Aromatic H, Donor Including Halogens, Donor Including Aromatic H + Halogens, and Custom.
By default, the feature type that matches a receptor polar hydrogen or a metal is set to Acceptor; for a receptor H-bond type it is Donor, and for a positional constraint it is Custom. Custom is undefined by default, so you must edit this feature to define the patterns that match the desired ligand atoms. For donors and acceptors, the feature type is coordinated with the choice made for treatment of halogens and aromatic hydrogens in the Settings - Advanced Settings dialog box. A change made in either place affects the setting in the other.
This button opens the Edit Feature dialog box, in which you can select the feature type; import or export feature sets; and add, edit or delete patterns. You must use this dialog box to provide feature definitions for positional constraints.
These options allow you to set the number of constraints in the group that must be satisfied when docking ligands.
All constraints that are selected (Use column checked) must be satisfied.
The number of constraints given in the text box must be satisfied. This number must be less than the number selected (Use column checked).
The total number of constraints that are required to match must be no more than 4. This number is the sum of required constraints within each group. For example, suppose Group 1 had two constraints selected for use, and both constraints were required to match; Group 2 had three constraints selected for use, but only one was required to match; and Group 3 and 4 had no constraints selected for use. The total number of required constraints is three: two from Group 1 and one from Group 2.
The limit on the number of required constraints is enforced when you select constraints.
Select this option to test whether poses satisfy constraints only after the ligands have been docked. With this option, constraints are used as a post-docking filter, rather than having any influence on the docking or scoring. You can therefore compare results directly with an unconstrained docking run.
Note: This option applies only to the constraints specified in the Constraints tab (receptor constraints). It does not apply to core constraints or to torsional constraints, which are ligand constraints.
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