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Receptor Grid Generation — Constraints Tab |
The Constraints tab of the Receptor Grid Generation panel is used to define Glide constraints for the receptor grids to be generated. Glide constraints are receptor-ligand interactions that you believe to be important to the binding mode. Up to ten constraints can be defined in a grid generation job. When you run Glide docking jobs, you can select as required interactions a subset of the constraints defined in the receptor grids, up to a limit of four. By setting such requirements, you can often significantly enrich the final results and speed up docking, as Glide is able to discard ligands, conformations, or poses that do not meet these criteria early on in their evaluation for docking suitability.
There are five types of constraints available: positional constraints, NOE constraints, H-bond constraints, metal constraints, metal coordination constraints.
The H atoms in flexible receptor groups cannot be used for constraints.
The total number of constraints that have been defined so far is displayed at the top of the tab:
N constraints have been defined (limit is 10 total)
The number N is the sum of the numbers of positional or NOE, H-bond/metal, and metal coordination constraints. These numbers are displayed in parentheses in the tabs of each subtab.
This subtab provides tools for defining positional and NOE (nuclear Overhauser effect) constraints. Positional constraints are defined as spheres that specified atoms of the ligands must occupy. NOE constraints are similarly defined as spherical shells (the region between two spheres) that specified atoms of the ligands must occupy.
This table displays the positional constraints you have chosen, giving the name and coordinates of the sphere center. For positional constraints a maximum distance is shown, which is the radius of the constraint sphere; for NOE constraints a minimum and a maximum distance are shown. The coordinates and the radius are given in angstroms. You can select a single constraint in the table, and edit the coordinates and radii of the spheres by clicking in the table cell and changing the value, or delete the constraint by clicking the Delete button.
This option is selected by default. The selected constraint is marked by a yellow sphere. The other positional constraints are marked by red spheres. Deselect this option to remove the markers.
This option is selected by default. If Show markers is selected, this option displays the name of the constraint in the Workspace. The labels are colored the same as the constraints. Deselect this option to remove the labels.
To add a positional constraint or an NOE constraint, click the New button. This button opens the New position/NOE dialog box, in which you can pick atoms with the standard picking controls to define the centroid of the constraint; name the constraint; select the constraint type (Position or NOE); specify the radius for a positional constraint, or the minimum and maximum distance for an NOE constraint. The position is the centroid of the selected atoms, and must be inside the enclosing box. While picking is in progress, the constraint is marked with a gray sphere. For NOE constraints, both spheres are displayed. When you click OK, the constraint is added to the table if it is inside the enclosing box; otherwise a warning is displayed.
To delete a single positional constraint, select it in the table and click Delete. To delete all the listed constraints, click Delete All.
The H-bond/Metal subtab contains controls for setting up hydrogen-bonding or metal constraints:
As you select atoms in the receptor, they appear in this table. Each constraint is identified by a name and an atom specification. A default constraint name is supplied. You can change the name by editing the table cell. The atom specification is given in the following format:
atom_number:chain: residue_name residue_number : atom_name : symmetry_set
where
For example:
341:C:ASN 239 : OD1: OD1
If the picked atom is part of a symmetry-equivalent set, its identification is followed by square brackets enclosing the number and name of each atom in the set, separated by commas:
2203:C:GLU 192 : OE2:[2203: OE2,2202: OE1]
Symmetry can be turned on or off by selecting or clearing the check box in the Use Symmetry column. If you clear the check box, only the atom that you pick is used for the constraint, and the symmetry information is removed from the Atom column. Symmetry is on by default.
When this option is selected, you can define H-bond/metal constraints by picking appropriate atoms in the receptor, which must be displayed in the Workspace. To define hydrogen bonds, pick any polar H, N, or O atom in the receptor. (The atom is identified in the status bar when the pointer is over the atom, as described in the Status Bar topic.) Glide automatically identifies symmetry-equivalent atoms as well, for example the other oxygen in a carboxylate group. The symmetry can be turned on or off in the Use Symmetry column. If it is on, any one of the symmetry-equivalent atoms will satisfy the constraint. If it is off, the atom that you picked is used for the constraint. To define metal sites, pick the metal atom.
This option is selected by default. A cross and padlock appear next to each atom picked, colored light blue for the selected constraint (the last one picked), and red for unselected constraints. If the picked atom is one of a set of symmetry-equivalent atoms, all the atoms in the set are marked. Deselect this option to remove the markers.
This option is selected by default. If Show markers is selected, this option displays the name of the constraint in the Workspace. The labels are colored the same as the constraints. Deselect this option to remove the labels.
To delete a single H-bond or metal constraint, select it in the table and click the Delete button. To delete all the listed constraints, click the Delete All button.
This subtab provides tools for defining constraints to possible coordination sites of a metal. For each metal, the available coordination sites are identified, based on the coordination of the metal to the receptor. A constraint sphere is placed at the ideal location of a ligand donor atom at the available site. This differs from the metal constraint feature, in which a constraint sphere is placed on the metal. The metal coordination constraint has directionality with respect to the metal, whereas the metal constraint has none. You can choose to use any or none of the sites found for a given metal.
This table displays the metal coordination constraints you have chosen, giving a name for the set of coordination sites associated with the metal, the coordinates of the ideal coordination sites, and the maximum distance of a constrained ligand atom from that site. You can edit the constraint name, the coordinates and the radii of the spheres by clicking in the appropriate table cell and changing the value.
When you select a row in the table, the rows for all the other sites associated with the metal atom are also selected, and the spheres are highlighted in the Workspace. Each table row has a column of check boxes that you can select or deselect to use or ignore each site. When you clear one of the check boxes, to ignore the site, the sphere in the Workspace is colored gray and made more transparent.
To delete the set of sites for a given metal, select a table row for the metal and click Delete.
Pick receptor metal atoms in the Workspace to define metal coordination constraints. (The atom is identified in the status bar when the pointer is over the atom, as described in the Status Bar topic.) When a metal is picked, the possible coordination sites are identified and rows are added to the Receptor metal atoms table with the coordinates of the sphere and the maximum distance. All of them are selected for use by default.
Rotate the set of coordination sites around the metal center. This may be necessary to adjust the orientations of the sites from their initial locations, so that the constraint spheres cover the desired regions of space. As coordination orientations can vary considerably in a complex structure such as a protein, it may be necessary to make some adjustments.
This option is selected by default. The selected set of coordination sites are marked with red spheres, and the other sets are marked with yellow spheres. Deselect this option to remove the markers.
This option is selected by default. If Show markers is selected, this option displays the name of the corresponding coordination site set in the Workspace on each sphere. Deselect this option to remove the labels.
To delete a single set of coordination sites, select one of the sites in the table and click the Delete button. To delete all the listed constraints, click the Delete All button.
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