LigPrep Panel

The LigPrep panel is used to to set up and start ligand preparation calculations. The main objective of LigPrep is to take 2D or 3D structures and produce the corresponding low-energy 3D structures for use by programs such as Glide and QikProp. The input and output can be in SD or Maestro format. LigPrep can produce multiple output structures for each input structure by generating different protonation states, stereochemistry, tautomers, and ring conformations.

To open this panel: click the Tasks button and browse to Ligand Preparation and Library Design → LigPrep (3D Conversion).

  • Using
  • Features
  • Additional Resources

Using the LigPrep Panel

To run a LigPrep job, choose a structure source, make settings in the panel, then click Run to run the job with the current job settings.

If you want to read panel settings from an input file, click the arrow next to the Settings button and choose Read, then choose the input file in the file selector that opens. The settings from the file are applied to the panel.

If you want to change the job settings, click the Settings button arrow and choose Job Settings. In the Job Settings Dialog Box, you can choose a job name,the host, and the number of subjobs (for a large job), and click Run to run the job.

If you obtain the structures from a file, the file can be in Maestro, SD, or SMILES format. The SMILES file can be in one of two formats:

  • .smi file—Text file with one SMILES string and an optional title per line
  • .csv file—Comma-separated file with SMILES string as the first field, title as the second, followed by optional properties.

The number of structures produced can vary a great deal, depending on the ligands being processed. The factors affecting the number of structures produced are described below:

  • In the Stereoisomers section, only Generate all combinations should result in many more structures. For individual ligands the increase can be as large as 2n, where n is the number of chiral centers. For large data sets the increase is typically around 1.5, but is very dependent on the classes of molecules being processed. You can reduce the number of structures produced by entering a smaller value in Generate stereoisomers (maximum), however this does increase the risk of missing important stereoisomers.

  • The Generate tautomers option typically increases the number of structures by less than 20%.

The structures that are produced can be filtered on the basis of various predefined descriptors. These descriptors are counts of various kinds of structural components, including a range of functional groups. You can filter the structures generated by LigPrep using a file that defines conditions on these descriptors. The descriptors are:

Num rings   Num heteroaromatic rings
Num aromatic rings   Num aliphatic rings
Num rotatable bonds   Num atoms
Molecular weight   Num chiral centers
Num neutral amines   Num amide hydrogens
Num divalent oxygen atoms   Num neutral donor groups
Num charged donor groups   Num neutral acceptor groups
Num charged acceptor groups   Num reactive groups
Num acidic hydrogens   Num donor groups
Num acceptor groups    

This file can be created by clicking Create, and constructing the list of criteria in the Ligand Filtering Panel. An example input file is given below. Comment lines start with ##.

##Remove molecules that have a molecular weight of greater than 650
Molecular weight >650.0
## Remove molecules with too many H-bond acceptor and donor atoms
Num acceptor groups >3
Num donor groups >3
##Remove molecules with fewer than 10 atoms
Num atoms <10

For syntax information, see the ligfilter Command Help. See also Filtering Structures by Property: ligfilter.

Generating large numbers of output structures (>150,000) in a single run can be very time consuming. If you want to generate large numbers of structures, you can distribute the LigPrep job across multiple processors on a multiprocessor host, by selecting the host and entering the number of processors in the Job Settings Dialog Box.

If structures cannot be processed for some reason, the input structures are copied to a file named jobname-failed.ext, which is in the same format as the input file. The structure numbers from the input file are reported at the end of a log file, along with the stage in which the failure occurred.

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 ligprep Command Help.

LigPrep Panel Features

Use structures from option menu

Choose the structure source for the current task.

  • Project Table (n selected entries)—Use the entries that are currently selected in the Project Table or Entry List. The number of entries selected is shown on the menu item. An icon is displayed to the right which you can click to open the Project Table and select entries.
  • Workspace (n included entries)—Use the entries that are currently included in the Workspace, treated as separate structures. The number of entries in the Workspace is shown on the menu item. An icon is displayed to the right which you can click to open the Project Table and include or exclude entries.
  • File—Use the specified file. When this option is selected, the File name text box and Browse button are displayed. The allowed file types are: Maestro, SD, SMILES (.smi) and CSV (.csv).
Open Project Table button

Open the Project Table panel, so you can select or include the entries for the structure source.

File name text box and Browse button

Enter the file name in this text box, or click Browse and navigate to the file. The name of the file you selected is displayed in the text box.

Filter criteria file text box and buttons

Enter the name of a file that contains criteria on molecular descriptors for filtering, click Browse to select an existing filter criteria file, or click Create to create a new filter criteria file in the Ligand Filtering Panel.

Maximum ligand size text box

Specify the maximum number of atoms allowed in any ligand. Ligands with more atoms are skipped.

Force field option menu

Choose the force field for minimization of structures. The choices are OPLS_2005 and OPLS4. The default is OPLS4 if it is available, otherwise it is OPLS_2005, unless you set the default in the Force Field settings section of the Preferences Panel.

Use customized version option

Use your customized version of the OPLS4 force field, rather than the standard version in the distribution. Only available when you choose OPLS4 from the Force field option menu and you have the appropriate license. This option is set by default to the value of the Use custom parameters by default option in the Preferences panel, under Jobs - Force field, when the current panel is opened. The default directory for the customized version can also be specified as a preference, in the same location.

If the customized version is missing or invalid, the text of this option turns orange and an orange warning icon is displayed to the right, with a tooltip about the problem.

Parameter set button

Select the set of custom parameters for the OPLS4 force field. Opens the Set Custom Parameters Location Dialog Box. Only available when you choose OPLS4 from the Force field option menu and you have the appropriate license.

Desalt option

Structures from some databases can consist of multiple molecules, one of which is the ligand. In many cases, the extra molecules are counter ions or water molecules. Select this option to remove all but the molecule with the largest number of atoms. If the desired molecule is not the largest, you may have to edit the structure in Maestro before passing it to LigPrep.

Generate tautomers option

For some ligand molecules, a tautomer of the commonly-given structure binds to the active site. Select this option to generate tautomers with significant populations for each input structure, up to 8 tautomers per input structure. LigPrep performs keto-enol tautomerization and the analogous sulfur and nitrogen tautomerizations, and histidine and DNA base tautomerizations. This option is recommended for preparing ligands for both Glide and QikProp calculations.

Stereoisomers section

Select the treatment of stereochemical information in the input and the generation of stereoisomers in the output. There are three options under the Computation heading that control the source of stereoisomers:

  • Retain specified chiralities (vary other chiral centers)— Keep the information on chiralities from the input file, and fix these chiralities for the entire calculation. Chirality information includes parities and bond directions from SD files, and the chirality property from Maestro files. Maestro chiralities are only written by sdconvert and the stereoizer utility. If the configuration or chirality of a chiral center is not specified, the two possible chiralities are generated in the output.

  • Determine chiralities from 3D structure— Discard all chirality information in the input file, and determine the chirality from the 3D geometry. These chiralities are held fixed. For centers whose chirality is indeterminate, structures for the two possible chiralities for each center are generated. (Sets the -g option of the ligprep command.)

  • Generate all combinations— Discard all chirality information, both from input file properties and from the 3D geometry, and generate all possible configurations that result from the combination of chiralities on each chiral center. (Sets the -ac option of the ligprep command.)

You can limit the number of stereoisomers to generate in the Generate at most N per ligand text box.

SD files in V2000 format have a field, the “chiral flag”, that determines whether the input structure represents a pair of enantiomers (0) or a stereoisomer (1). Select For SD V2000 input, generate enantiomers if the chiral flag is 0, if you have SD input and want both enantiomers to be generated if the chiral flag in the SD file is set to zero. The default is to generate only the enantiomer represented by the specified chiralities. This setting is stored as a preference, so it is preserved across Maestro sessions.

When varying chiralities, chemically reasonable chiralities are initially assigned for steroids, fused ring systems, and peptides. When stereoisomers are generated for fused ring systems, the correlation between chiralities on chiral centers in the rings is taken into account, and invalid combinations are not generated.

For any of these settings, the internally generated stereoisomers are subjected to a filtering step to eliminate some structures that either violate geometric restrictions for fused ring systems or conflict with natural product chiralities (e.g. the pattern of chiralities in steroid frameworks). See Chirality Manipulations Using Maestro and LigPrep for more information.

Output format options

Specify the file format for the output file. If you want to incorporate the structures into the current project, you must select Maestro for the format. In Maestro format, the structures are written to the file jobname.maegz. In SDF format, the structures are written to the file jobname.sdf.

Job toolbar

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

The Job Settings button opens the LigPrep - 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.

Tutorials

Quick Reference Sheets

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