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Ligand Docking — Settings Tab |
The Settings tab defines the basic options for docking ligands using previously calculated grids. Use this tab to select the type and precision of docking job you want to run and make settings for ligand sampling.
Glide has the following precision options on this option menu:
High-throughput virtual screening (HTVS) docking is intended for the rapid screening of very large numbers of ligands. HTVS has much more restricted conformational sampling than SP docking, and cannot be used with score-in-place. Advanced settings are not available for HTVS, but are fixed at predetermined values.
Standard-precision (SP) docking is appropriate for screening ligands of unknown quality in large numbers.
Extra-precision (XP) docking and scoring is a more powerful and discriminating procedure, which takes longer to run than SP. XP is designed to be used on ligand poses that have been determined to be high-scoring using SP docking. We recommend that you run your database through SP docking first, then take the top 10% to 30% of your final poses and dock them using XP, so that you perform the more expensive docking simulation on worthwhile poses.
Note: Extra precision mode can be used when the active site of the complex contains a metal and often works well but has not been optimized for such applications.
Standard-precision docking for peptide ligands uses the same general settings as for regular standard precision but changes some of the settings to enhance the retention of poses. Specifically, it keeps 100000 poses in the initial docking stage, and uses 1000 poses per ligand for energy minimization, and sets the number of poses for post-docking minimization to 100. Although this option was designed for peptides, it is not restricted to peptides: you can dock any kind of ligand.
If you select this option, the grid must be one that was generated for this mode, i.e. with Generate grid suitable for peptide docking selected in the Receptor tab of the Receptor Grid Generation panel.
The Ligand sampling option menu allows you to choose whether ligands are docked flexibly, rigidly, or not at all (score in place). Extra options are available for flexible docking.
Sample inversions at pyramidal nitrogen atoms (not amides).
Sample the conformations of rings. These conformations are not sampled in the main conformation generation, which focuses on sampling of rotatable bonds, leaving the core fixed. This option is selected by default. Deselect this option if you want rings to remain in their input conformations throughout docking.
Select this option if you want to include the input conformations of rings in addition to other conformations. This option is deselected by default, and is only available if Sample ring conformations is selected.
Bias the sampling of torsions for groups that are expected to adopt a particular conformation towards that conformation, by freezing angles, or applying filters or penalties.
Apply torsion controls to direct a set of predefined functional
group torsions to adopt certain conformations. These functional groups and the
type of biasing are defined in a resource file (torcontrol.txt, in
impact-vversion/data).
This option applies constraints or penalties to rotation around amide C–N bonds. The option menu provides a choice of the constraint type:
Do not penalize or constrain rotations about certain bond types, but allow them to adopt a conformation according to the force field.
Rigid docking allows the existing ligand structure to be translated and rigidly rotated relative to the receptor, but skips the conformation generation step.
With this option, the input ligand structure does not pass through the Glide docking procedure, but the input coordinates are used to perform an optimization of the ligand structure in the field of the receptor, and then the ligand is scored. For HTVS and SP, a minimization is performed; for XP, the ligand is regrown in place. With XP mode, this option is not a substitute for a full XP docking calculation. XP mode requires good initial poses.
When this option is selected, Glide does no docking, but rather uses the input ligand coordinates to position the ligands for scoring. This option is useful to score the reference ligand in its cocrystallized or modeled position, or as a post-processing step on Glide-generated poses to obtain individual components of the GlideScore prediction of the binding affinity.
Note: you cannot score in place a ligand that is currently defined in Maestro as the reference ligand.
Write information on XP scoring terms to a file that can be read by the Glide XP Visualizer. This option is available if XP is selected under Precision. This option is not available with SD format for the output pose file.
Note: To generate XP descriptor information, you must have a license for this feature.
If the ligands have been prepared using Epik for ionization and tautomerization, the Epik penalties for adopting higher-energy states (including those where metals are present) are added to the docking score when this option is selected. Ligands that do not have this information are not penalized and will therefore have better scores, so you should ensure that the ligand set is consistent.
If the ligand interacts with a metal (distance less than 3.0 Å), the metal penalties that are computed when Epik is run with the metal binding option are used. If multiple ligand atom-metal interactions are found, the smallest value of the metal-specific penalty is used.
Add a reward for each intramolecular hydrogen bond to the GlideScore. A contribution is also added to Emodel for each intramolecular H-bond. Intramolecular ligand hydrogen bonds can be important for binding.
Increase the torsional potential around bonds between atoms whose geometry should be planar (i.e. sp2 atoms). This option should make aromatic rings, amides, esters, and so on, less likely to adopt a nonplanar geometry.
If the grid has excluded volumes associated with it, select this option to apply all the excluded volumes, and choose the penalty level from the option menu. The penalty is applied if any ligand has atoms within the excluded volume. The penalty ramps up from the boundary of the volume over a short distance to the maximum penalty.
Display in the Workspace the excluded volume spheres that are associated with the grid.
Click this button to open the Settings - Advanced Settings dialog box. This dialog box provides options for ligand conformer generation, selection of initial poses, energy minimization, and inclusion of aromatic H-bonds and halogen bonds.
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