Ligand Docking

Note: Jobs run with the Ligand Docking panel will use the optimized Glide.

The Glide Ligand Docking panel is used to set up and run docking jobs using previously calculated receptor grids. To generate receptor grids, see the Receptor Grid Generation Panel topic.

To open this panel: click the Tasks button and browse to Receptor-Based Virtual Screening → Ligand Docking.

  • Using
  • Features
  • Additional Resources

Using the Ligand Docking Panel

Glide ligand docking jobs require a set of previously calculated receptor grids and one or more ligand structures. Preparation of the ligands before docking is strongly recommended. LigPrep or MacroModel can be used to prepare ligands. If a correct Lewis structure cannot be generated for a ligand, it will be skipped by the docking job.

If you want to dock a set of ligands using a progression of precision, you can use the Virtual Screening Workflow to set up and run the docking jobs. See Virtual Screening Workflow for details.

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 glide Command Help. See also Running Glide from the Command Line.

Ligand Docking Panel Features

Active Learning button

When this button is blue, the Active Learning mode is activated, and the available options for this panel are different from those when Active Learning is deactivated (in both the Docking Setup and Biases and Constraints tabs). Click the blue button to deactivate Active Learning, turning the button gray. Click the gray button again to reactivate Active Learning mode. The available options for each mode are described in the tabs below with the "with Active Learning" name.

Configure settings for menu

This option is disabled by default, and appears when Active Learning mode is deactivated. From the menu, you may configure settings for Small molecules, Peptides, Macrocycles, and Fragments.

Note: Changing this option modifies some default settings to optimize the calculations for your structure. Select the option that corresponds most closely to your structures. If the Fragments option is selected, the changes will include some hidden (command-line only) settings.

  • Docking Setup (with Active Learning)
  • Docking Setup
  • Biases and Constraints (with Active Learning)
  • Biases and Constraints

Docking Setup (with Active Learning) Features

Inputs

Training options

Docking options

Outputs

Inputs

Receptor grid button

Load the receptor grid for docking of the training set. The button is labeled Load File. Opens a file chooser to locate and load the grid. For more information on the Glide grid, see Receptor Grid Generation Panel. The status of the grid is reported to the right of the button.

Ligand button

Click this button, labeled Add Files, to add files that contain the ligand structures, in SMILES format. A file selector opens, in which you can select multiple files of type .csv or .smi (but not both types).

You can specify multiple files to screen either by selecting them in the file selector, or clicking the button multiple times. All .csv files must have the same columns for the SMILES string and the title. To remove files from the list, click the change link. A small pane opens with a list of files, which you can select and remove.

The.smi file must contain only two columns, with the SMILES in the first and the title in the second. For .csv files with two columns, the file is imported directly if the two columns have the headings smiles and title (case-insensitive). Otherwise the Import SMILES Dialog Box opens, so you can choose which columns contain the SMILES string and the title.

The number of files is displayed to the right of the button. To clear the file selection, click the X displayed to the right of the button.

Preparation Options link

Specify options for preparation of the ligands for docking. Opens the Ligand Preparation Options Dialog Box.

Training options

Sample size per round text box

Use the text box to enter a value for the sample size per round, in concert with the menu to select units of thousand ligands or hundred ligands corresponding to the entered value. Note that increasing this value increases the memory required for training.

Diverse menu

Choose the criterion by which ligands are selected. The current choice is displayed as the link text.

  • Random—choose the ligands at random.
  • Diverse—choose a diverse set of ligands (the default).
  • Most uncertain—choose the ligands with the highest uncertainty in the predicted docking score.
Training time menu

Choose the amount of training time to use per round, from the following. The training of the models stops after the amount of time has been used, and the best model found to that point is used. Using more time than the standard could improve the models if they are not already well fit.

  • Standard (4 hours)
  • Extended (8 hours)
  • Maximum (12 hours)
Number of rounds text box

Specify the number of rounds of training to use for the model.

Run pilot only option

Run a pilot job to assess the effectiveness of active learning on the input library before submitting a full run. Sets Number of rounds to 1 and disables it; the number of rounds is restored when you clear this option. The pilot job samples a pilot library of 50k ligands from the input ligand file and runs a modified active-learning workflow optimized for a short run time, with a training set size of 5k ligands. Separately, the entire pilot library is docked with Glide. A summary report is generated, capturing the effectiveness of active learning on this library.

Docking options

Active biases link

Clicking the link will open the Biases and Constraints (with Active Learning) tab.

Advanced Settings link

This button opens the Ligand Docking (Beta) Advanced Settings (Active Learning), in which you can set options including Aromatic H and Halogen H-bonds, Pose Filtering, and Energy Adjustments.

Outputs

Dock and import best ligands text box

In the text box, enter a percentage value and use the arrow keys to adjust. The total estimation will appear to the right of the text box, and will update automatically when the values are changed.

Estimated time to completion change link
The text displays the estimated time to completion based on panel settings, license availability, and the estimated ligand count. Clicking the link opens a pane with options to adjust Estimated resources (CPUs for AutoQSAR and Glide licenses) and Inputs (approximate number of ligands).

Docking Setup Features

Inputs

Docking options

Outputs

Inputs

Receptor grid menu

Choose a source for the receptor grid. The menu has two options: Browse file and Create New. Click Browse file to select a grid to dock to. The grid file must be accessible to the host on which you are running Maestro. Clicking Create New opens the Receptor Grid Generation Panel).

If you plan to use SP-Peptide docking (Configure settings for: Peptides selected), you must select a grid that was generated for this docking mode (with Generate grid suitable for peptide docking selected in the Receptor tab of the Receptor Grid Generation Panel). If you plan to use any of the other three configurations, you must not select a grid generated for SP-Peptide docking.

Note: If you want to use grids from earlier releases in which the grid was not compressed, you can also choose the .grd file for the grid to use that grid

The Display link is enabled when a grid is loaded, click an option from the menu to display Receptor and/or Grid Boxes.

Ligand source menu

Choose the source of the ligands from this option menu, from the following options:

  • Workspace (included entries) — Dock the structures in the Workspace. If you select this option, the entries in the Workspace must all be valid ligands, as described above. You must ensure that the structures in the Workspace satisfy the requirements.

  • Project Table (selected entries) — Dock ligands that are selected entries in the Project Table. For more information about the Project Table and entry selection, see the Project Table Panel topic.

  • File — Dock ligands from one or more files. Enter the file names in the File name text box, or click the Browse button to navigate to and select the ligand files.

    The files can be in any of the supported formats (Maestro, SD, MOL2, PDB, SMILES), but you can only have files of one format in a single job. By default, all structures in each file are docked. LigPrep is run automatically on the generated 3D structures from the SMILES input. You can specify LigPrep options by clicking the Preparation Options link and making the settings in the Ligand Preparation Options Dialog Box.

    If you select a single file, you can specify a particular range of ligands to dock, using the Range controls:

    • To start at a ligand other than the first, edit the value in the first text box.
    • To end at a value other than the last, deselect End and edit the value in the second text box.

    If a Glide job run with a single ligand file terminates abnormally, you can set the initial ligand number to pick up after the point in the input ligand file at which the problem occurred.

  • Phase Database — Extract the ligands from a Phase database. Specify the path to the database or click Browse and navigate to the database in the file selector that opens. Phase databases have the extension .phdb. Older databases (ending in _phasedb) must be converted first, with phase_database.

    You can restrict the ligand set to the subset of the database specified in the Subset text box. Enter the path to the subset or click Browse and navigate to the database subset in the file selector that opens. The subset has the extension _phase.inp.

Options link
Clicking the link opens a separate pane with the following options.
Limit ligands to be docked and scored by: section

  • Number of atoms - maximum text: enter a value in the text box and use the arrow buttons to adjust. The default value is 500.

  • Number of rotatable bonds - maximum: enter a value in the text box and use the arrow buttons to adjust. The default value is 100.

  • Range in files allow: select an option for either All (1 to End) or Subset.

Use partial charges from input files: select this option to enable, it is disabled by default.

Scaling of van der Waals radii (nonpolar atoms): section

  • Scaling factor: enter a value in the text box and use the arrow buttons to adjust. The default value is 0.80.

  • Partial charges cutoff: enter a value in the text box and use the arrow buttons to adjust. The default value is 0.15.

Note: To soften the potential for nonpolar parts of the ligand, scale the vDW radii of ligand atoms with partial atomic charge (absolute value) less than the specified cutoff. No other atoms in the ligand will be scaled.

Docking options

Ligand sampling option menu and options

The Ligand sampling option menu allows you to choose whether ligands are docked flexibly, rigidly, or none (with options to refine only, or to score in place). Extra options are available for flexible docking.

Flexible

This is the default choice and directs Glide to generate conformations internally during the docking process; this procedure is known as "flexible docking". Conformation generation is limited to variation around acyclic torsion bonds, sampling of low-energy ring conformations, and generation of pyramidalizations at certain trigonal nitrogen centers, e.g. in sulfonamides. For a set of predefined functional groups, such as amides and esters, you can bias sampling of the torsion around the bond that normally adopts a particular conformation so that it adopts the desired conformation.

There are several options for conformation generation with this choice:

Sample nitrogen inversions option

Sample inversions at pyramidal nitrogen atoms (not amides). This option is selected by default.

Sample ring conformations option

Sample the conformations of rings, using the same technology as in LigPrep—see Ring Conformations: ring_conf for details. These conformations are not sampled in the main conformation generation, which focuses on sampling of rotatable bonds, leaving the core fixed. Deselect this option if you want rings to remain in their input conformations throughout docking.

This option is selected by default. The two following options are made available if this option is selected.

Sample macrocycles using Prime option

Sample the conformations of macrocycles using the Prime macrocycle sampling code (see Prime Macrocycle Sampling Panel), with special options for Glide docking. These conformations are not sampled in the main conformation generation, which focuses on sampling of rotatable bonds, leaving the core fixed. This option changes settings for the number of poses in various stages of the docking process.

Sampling of macrocycles can take from a few minutes to an hour per ligand. The job is split into subjobs for each individual ligand., which can be distributed over multiple processors. Docking results are only generated for macrocyclic ligands: non-macrocycles are skipped.

If you want to split your input file into macrocycles and non-macrocycles before docking, you can use the following command in a terminal window (Linux or Mac, prepended with $SCHRODINGER/) or a Schrodinger shell (Windows):

run -FROM glide split_macrocycles.py

Run the command with the -h option for the full syntax, including description of input and output files.

This option is deselected by default, and is only available if Sample ring conformations is selected. This option requires a Prime license and a Macrocycle license in addition to a Glide license.

Include input ring conformation option

Select this option if you want to include the input conformations of rings in addition to other conformations. The conformational sampling uses the input conformation as a seed, and does not necessarily include it in the set of conformations returned.

This option is deselected by default, and is only available if Sample ring conformations is selected.

Bias sampling of torsions for options

Choose an option for sampling of torsions that should normally be restricted to a particular conformation. The biasing can include retention of the input conformation, setting the torsion to a particular value, applying a penalty for deviating from the desired conformations, or allowing only a particular conformation to within a small angle range. The options cover different selections of functional groups:

Predefined functional groups

Bias the sampling of torsions for a set of functional groups that is defined in a resource file (default). The choice of biasing method, as outlined above, is set in the resource file. The resource file can be customized—see Customizing Torsional Controls for Docking Planar and Other Groups.

Amides bonds only

This option applies constraints or penalties to rotation around amide C–N bonds. The option menu provides a choice of the constraint type:

  • Penalize non-planar conformation—penalize amide bonds that are not cis or trans (default)
  • Retain original conformation— freeze amide bonds in their input conformation throughout docking
  • Allow trans conformation only—enforce trans conformation within a small angle range (20°). Ligands that do not dock in this range are rejected.
None

Do not penalize or constrain rotations about certain bond types, but allow them to adopt a conformation according to the force field.

Use alternate sampling option
This option is enabled primarily for use in fragment docking. When enabled, this option bypasses the elimination of poses during rough scoring stage, leading to many more poses being passes along to the later stages.
Rigid

Rigid docking allows the existing ligand structure to be translated and rigidly rotated relative to the receptor, but skips the conformation generation step. Note: The Settings link is disabled when this option is selected.

None, with toggle
Selecting the None option with cause a link to appear. Clicking the link opens a menu to select Refine only, or Score in place only. The link text will update with the selection made. The details for these options are explained below: 
    None (refine only)

    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. The goal of this docking method is to find the best-scoring pose that is geometrically similar to the input pose. 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 accurate initial poses.

    None (score in place only)

    When this option is selected, Glide does no docking, but rather uses the input ligand coordinates to position the ligands for scoring. It therefore requires accurate initial placement of the ligand with respect to the receptor.

    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. It can also be used to check whether the scores of the known binders in their native proteins are similar enough to their scores when cross-docked to the chosen receptor protein. If this is the case, it is reasonable to expect that similar structures would also score well.

    This option should not be used with Glide XP, as full XP sampling is normally needed to avoid strong XP penalties for ligands that should be able to dock correctly.

    Note: you cannot use score in place for the ligand that is defined as the reference ligand for calculation of the RMSD in conformational comparisons.

Precision option menu

Choose a docking precision option:

HTVS (high throughput virtual screening)

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.

SP (standard precision)

Standard-precision (SP) docking is appropriate for screening ligands of unknown quality in large numbers.

SP-Peptide

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.

Perform post-docking minimization option and settings

This option allows you to perform a minimization of the poses following the final docking, and can be used for both flexible and rigid docking. The minimization optimizes bond lengths and angles as well as torsional angles, and rescores the poses using the scaled Coulomb-van der Waals term and the GlideScore. The full force-field minimization performed by post-docking minimization penalizes highly strained ligand geometries and eliminates poses with eclipsing interactions, many intraligand close contacts, and so on. If the binding pocket is small, or the ligands are fairly rigid, the post-docking minimization will not improve the results for poses that do not fit or are already poorly aligned to the receptor.

The docking process relies on rapid generation of ligand conformers and use of a grid to represent the receptor. The ligand poses generated during docking are rarely exactly at a local minimum, and post-minimization can improve the geometry of the poses. The Grid Minimization step of the Glide funnel does not perform a full force-field minimization and excludes interactions beyond 1,5 interactions. Thus, post-docking minimization can improve the poses.

The time taken for post-docking minimization is less than 1% of the total docking time for SP and XP docking, and can be around 10% for HTVS.

Active biases link

Clicking the link will open the Biases and Constraints tab.

Options link
Click the link to open a separate pane with the following options:
Docking section

  • Add Epik state penalties to docking score — 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.

  • Apply excluded volumes penalties option and menu — 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 value of the penalty ramps up from zero at the boundary of the volume to the maximum penalty at 90% of the sphere radius. The penalty is applied in both the rough scoring stage and the final docking

  • Show excluded volumes when the receptor is shown — Display in the Workspace the excluded volume spheres that are associated with the grid. Only available if the grid has excluded volumes and Apply excluded volumes penalties option is selected.

Minimization section

Include strain correction in post-docking score: — Apply strain correction terms when doing the final scoring. These terms are evaluated by optimizing each ligand pose as a free ligand, first with constraints on all torsions, then without these constraints. The difference is used to compute a penalty term for unreasonably high strain: the strain correction is only added if it is above a threshold, and the excess strain above this threshold is scaled before adding it to the GlideScore. The strain corrections are stored as Maestro properties for each pose, corresponding to the strain values reported in the log file. Another more flexible approach is available in the Strain Energy Calculation and Rescoring Panel.

Advanced Settings link

This button opens the Ligand Docking (Beta) Advanced Settings, in which you can set options to screen out poses that either have too high an energy or are too similar to other poses, and change the parameters associated with strain correction.

Outputs

File format option menu

From the menu, choose either Pose Viewer file (includes receptor), or Ligand Poses (no receptor).

Maximum # of poses to save per ligand text box

Enter a value to set the maximum number of poses to save per ligand. The default value is 1.

Also limit total number of poses saved - best option and text box

Enable this option and enter a value to limit the total number of the predicted best-binding poses written to the sorted pose file. By default, all poses that pass the filters are reported. If you are docking a large number of ligands and want multiple poses per ligand, the pose file may take up a large amount of disk space.

More Options link
Click the link to open a separate pane with the following options:
Write per-residue interaction scores option and settings

Write out per-residue interaction scores for a specified set of residues. The Coulomb, van der Waals, and hydrogen bonding scores, the sum of these three (Eint), and the minimum distances are calculated between the ligand and the specified residues. These values are written as structure-level properties for each ligand to the pose file, as well as to the log file. The residues can be specified by selecting one of the options described below.

Per-residue interactions can be visualized in the Workspace when viewing poses. See Viewing Poses for more information.

For residues within N Å of grid center option and text box

Write scores for complete residues that have any atom within the specified distance of the grid center.

Pick residues to include option and Specify Residue button

Pick the residues for which the scores are written. The residues are specified by clicking Specify Residue and using the picking controls in the Residues for Per-Residue Interaction Scores Dialog Box DEPRECATED.

Compute RMSD to input ligand geometries option

Compute the RMSD between the docked poses and the corresponding input ligand geometries. The RMSD calculation is done in place with heavy atoms only. The value is recorded as a Maestro property, named Glide rmsd to input (internal name r_i_glide_rmsd_to_input).

Advanced Settings link

This button opens the Ligand Docking (Beta) Advanced Settings, in which you can set options to screen out poses that either have too high an energy or are too similar to other poses, and change the parameters associated with strain correction.

Biases and Constraints (with Active Learning) Tab Features

The Biases and Constraints (with Active Learning) tab is divided into subtabs, for different kinds of constraints.

  • Receptor
  • Torsional

Receptor Tab Features

The Receptor tab contains four subtabs for defining constraint groups. Each subtab has the same structure.

Show markers option

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.

Group tabs

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.

Available constraints table

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 number of constraints you selected is displayed next to the table title. The table columns are described below. Any given constraint can only be used in one constraint group. If selected in one group, a given constraint will be disabled in other groups.

Use

Check box to select the constraint for use in docking. Click to select or deselect.

Name

Constraint name. This is the name defined in the Constraints tab of the Receptor Grid Generation Panel.

Receptor Constraint 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).

Ligand Feature

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 DEPRECATED. A change made in either place affects the setting in the other.

Edit Feature button

This button opens the Edit Feature Dialog Box DEPRECATED, 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.

Must match options

These options allow you to set the number of constraints in the group that must be satisfied when docking ligands.

All option

All constraints that are selected (Use column checked) must be satisfied.

At least option and text box

The number of constraints given in the text box must be satisfied. This number must be less than the number selected (Use column checked). For example, if you chose three hydrogen-bond acceptors, and you want any two out of the three to be satisfied, you would enter 2 in the text box.

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.

Test Constraint Satisfaction Only After Docking Option

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.

Torsional Tab Features

In this tab you can set up torsional constraints for all ligands. This is done by defining SMARTS patterns that are matched in the ligands, and sets of torsions that are constrained relative to those SMARTS patterns.

This tab is only available when either Dock flexibly or Refine is selected in the Settings tab. All constraints defined in this tab are applied during docking.

Patterns table

This table lists the SMARTS patterns used to define the torsional constraints. The SMARTS pattern cannot be edited. If you want to modify a pattern, you will have to create a new one, and delete the old one.

SMARTS pattern SMARTS pattern that is to be used for a constraint.
Atoms Number of atoms in the SMARTS pattern
Torsions Number of torsions that are defined (and constrained) for the SMARTS pattern. Set to All if all torsions are constrained using the Constrain options below.
Pattern action buttons

These buttons perform actions on the rows of the Patterns table.

New button

Create a new SMARTS pattern in the table. Opens the New Torsion Pattern dialog box, in which you can type in a SMARTS pattern or get the SMARTS pattern from the current Workspace atom selection.

Delete button

Delete the rows that are selected in the table.

Delete All button

Delete all rows in the table.

Constrain options

These options allow you to choose which torsions to constrain.

  • All torsions—Constrain all torsions for the pattern that is selected in the table, subject to the conditions for a torsion to be valid for use as a constraint.
  • Selected torsions—Constrain the torsions that are listed in the torsions table, below. When you select this option, the torsions table and related tools become available.
Torsions table

This table lists the torsions that have been selected for use as constraints for the pattern that is selected in the Patterns table.

Atoms List of atom indices in the SMARTS pattern that define the torsion (noneditable).
Set Angle Check boxes for setting the corresponding angles to the value specified in the Angle column for each ligand.
Angle Angle to which the torsion should be constrained in all ligands. By default, the torsion is constrained for each ligand to the value it had when it was read by Glide. You can edit this table cell to change the angle.
Pick atoms to add a torsion option

Select this option to pick torsions in the Workspace. Four atoms must be picked to define the torsion. The atom indices (as defined by the SMARTS pattern) are listed in the Atoms column of the torsions table when the fourth atom is picked, and the angle in the Workspace structure is shown in the Angle column. The atoms must form a contiguous set of three bonds when you have finished picking, and must not define a ring torsion. They must also be atoms in the SMARTS pattern for which you are defining torsions. No checking is done for the validity of the torsion prior to docking, so you must make sure that it meets the criteria given above. The torsion cannot be edited once you have defined it, so if it is in error, you must delete it.

Delete and Delete All buttons

Delete the rows that are selected in the table, or delete all rows in the table.

Biases and Constraints Tab Features

The Biases and Constraints tab is divided into subtabs, for different kinds of constraints.

  • Receptor
  • Core
  • Shape
  • Torsional

Receptor Tab Features

The Receptor tab contains four subtabs for defining constraint groups. Each subtab has the same structure.

Show markers option

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.

Group tabs

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.

Available constraints table

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 number of constraints you selected is displayed next to the table title. The table columns are described below. Any given constraint can only be used in one constraint group. If selected in one group, a given constraint will be disabled in other groups.

Use

Check box to select the constraint for use in docking. Click to select or deselect.

Name

Constraint name. This is the name defined in the Constraints tab of the Receptor Grid Generation Panel.

Receptor Constraint 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).

Ligand Feature

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 DEPRECATED. A change made in either place affects the setting in the other.

Edit Feature button

This button opens the Edit Feature Dialog Box DEPRECATED, 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.

Must match options

These options allow you to set the number of constraints in the group that must be satisfied when docking ligands.

All option

All constraints that are selected (Use column checked) must be satisfied.

At least option and text box

The number of constraints given in the text box must be satisfied. This number must be less than the number selected (Use column checked). For example, if you chose three hydrogen-bond acceptors, and you want any two out of the three to be satisfied, you would enter 2 in the text box.

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.

Test Constraint Satisfaction Only After Docking Option

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.

Core Tab Features

In this tab you can specify the core of a reference ligand, and use it to perform core RMSD measurements of docked ligand poses or to restrict docked poses to those that lie within some RMSD tolerance of the reference core.

The constraint that you apply here is a ligand-based constraint, which means that the ligands that are subject to the constraint are those that have the same core moiety as the reference ligand. Ligands that do not match the core can be screened out in the first docking stage. In later stages, ligands that match the core pattern but do not meet the rms tolerance for the position of the core can be screened out.

Core Pattern Comparison controls

The Core pattern comparison controls allow you to choose which task to use the core definition for.

Use core pattern comparison option

Select this option to use a core definition for comparison or constraint. This option is off by default. When you select this option, the rest of the options in the tab are enabled.

Use for RMSD calculations only option

Use the core definition for computing the RMSD from the reference ligand, but not for docking.

Restrict docking 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 or pattern, it can be skipped.

Tolerance text box

Enter a tolerance for the RMSD in angstroms for restricting the docking to the reference position in this text box.

Retry with less tight core constraints (1.0 Å) if poses are rejected option

If the poses are rejected with tight core constraints and the core-snapping algorithm, try again with the filtering algorithm and a core constraint tolerance of 1.0 Å. This option is turned off and not available if the tolerance is set to more than 0.75 Å, as the filtering algorithm becomes the default at that tolerance.

Define core section

In this section you can define the core of the reference ligand, that is, the atoms that are used for comparison or constraint.

Pick core-containing molecule option

This option allows you to pick the molecule to use for the core. The molecule is marked in purple in the Workspace if Show markers is selected. It is automatically selected when the controls in this section become available. You must pick a core-containing molecule before you can proceed to define the core atoms. If you also define shape constraints, you must pick the same ligand for both types of constraint.

This option is automatically deselected if you choose SMARTS pattern for the Core atoms option, as the core is not defined by a molecule.

Show markers option

This option displays markers for the core-containing molecule and for the SMARTS pattern and RMSD subset atoms, as appropriate. It is selected by default, as there is no other indication of the picked atoms or molecules.

Core atoms options

These options are used to define the core atoms in the core-containing molecule:

  • Maximum common substructure—the core atoms are determined for each ligand independently from the maximum common substructure of the ligand and the core-containing molecule.

  • All heavy atoms—the core atoms are all non-hydrogen atoms in the picked core-containing molecule.

  • All atoms—the core atoms are all atoms in the picked core-containing molecule.

  • SMARTS pattern—the core atoms are defined in terms of a SMARTS pattern, not a molecule. 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. Note that it is advisable to not have the receptor displayed when you click Get From Selection, because it can slow the generation of the SMARTS pattern.

    The atoms in the Workspace structure that match the pattern are marked with green markers, if Show markers is selected. You can also define a subset of these atoms with which to evaluate the RMSD by selecting Pick RMSD subset atoms, then picking the atoms. A lock symbol appears next to the atoms you pick. Each pick adds to the set; picking an atom again removes it from the set.The RMSD atoms are used both when calculating only the RMSD and when restraining the core: it is the RMSD of these atoms that must fall below the prescribed tolerance in the latter case.

    This option disables the Pick core-containing molecule option.

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 (i.e. it is discarded in the first stage of the funnel). 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.

Shape Tab Features

Specify constraints to the shape of the reference ligand (or part of it).

Apply shape constraints option

Apply the constraints on the ligand shape that are set in this tab. When selected, the other options are activated.

Define reference shape section

Define a reference ligand to which the docked ligands are constrained by shape. If you also define core constraints, you must use the same reference ligand.

Workspace ligand option and text box.

Select this option to define the shape to match as that of a ligand in the Workspace, or part of it. This text box shows the ASL expression for the picked ligand. If you also define core constraints, you must pick the same ligand for both types of constraint.

Pick option

Select this option to pick the ligand in the Workspace. The ASL expression is filled in when you pick.

Show markers option

Show markers on the picked ligand, so you can identify it if there are multiple ligands in the Workspace.

File name text box and Browse button

Enter the reference ligand file name in this text box, or click Browse and navigate to the reference ligand file. The name of the reference ligand file you selected is displayed in the text box. The allowed file types are: Maestro. The ligand in this file is used as is to define the shape to match.

Use selected atoms only option and text box

Use only the atoms that are selected in the Workspace to define the shape. The noneditable text box shows the selected atoms, and is populated when you click Load Workspace Selection.

Load Workspace Selection button

Select the atoms you want to use for the shape in the Workspace, and click this button to use these atoms. The atom numbers are displayed in the text box.

Torsional Tab Features

In this tab you can set up torsional constraints for all ligands. This is done by defining SMARTS patterns that are matched in the ligands, and sets of torsions that are constrained relative to those SMARTS patterns.

This tab is only available when either Dock flexibly or Refine is selected in the Settings tab. All constraints defined in this tab are applied during docking.

Patterns table

This table lists the SMARTS patterns used to define the torsional constraints. The SMARTS pattern cannot be edited. If you want to modify a pattern, you will have to create a new one, and delete the old one.

SMARTS pattern SMARTS pattern that is to be used for a constraint.
Atoms Number of atoms in the SMARTS pattern
Torsions Number of torsions that are defined (and constrained) for the SMARTS pattern. Set to All if all torsions are constrained using the Constrain options below.
Pattern action buttons

These buttons perform actions on the rows of the Patterns table.

New button

Create a new SMARTS pattern in the table. Opens the New Torsion Pattern dialog box, in which you can type in a SMARTS pattern or get the SMARTS pattern from the current Workspace atom selection.

Delete button

Delete the rows that are selected in the table.

Delete All button

Delete all rows in the table.

Constrain options

These options allow you to choose which torsions to constrain.

  • All torsions—Constrain all torsions for the pattern that is selected in the table, subject to the conditions for a torsion to be valid for use as a constraint.
  • Selected torsions—Constrain the torsions that are listed in the torsions table, below. When you select this option, the torsions table and related tools become available.
Torsions table

This table lists the torsions that have been selected for use as constraints for the pattern that is selected in the Patterns table.

Atoms List of atom indices in the SMARTS pattern that define the torsion (noneditable).
Set Angle Check boxes for setting the corresponding angles to the value specified in the Angle column for each ligand.
Angle Angle to which the torsion should be constrained in all ligands. By default, the torsion is constrained for each ligand to the value it had when it was read by Glide. You can edit this table cell to change the angle.
Pick atoms to add a torsion option

Select this option to pick torsions in the Workspace. Four atoms must be picked to define the torsion. The atom indices (as defined by the SMARTS pattern) are listed in the Atoms column of the torsions table when the fourth atom is picked, and the angle in the Workspace structure is shown in the Angle column. The atoms must form a contiguous set of three bonds when you have finished picking, and must not define a ring torsion. They must also be atoms in the SMARTS pattern for which you are defining torsions. No checking is done for the validity of the torsion prior to docking, so you must make sure that it meets the criteria given above. The torsion cannot be edited once you have defined it, so if it is in error, you must delete it.

Delete and Delete All buttons

Delete the rows that are selected in the table, or delete all rows in the table.

Job toolbar

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

The Job Settings button opens the Ligand Docking - 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.