Create Phase Database Panel

Create Phase Database Panel Features

• Input tab
  • Task section
    • Choose task options
    • Job will run on localhost option
    • Database path text box and Browse button
    • Database path text box and Browse button
  • Ligands section
    • Use ligands from option menu
    • Input structure file text box and Browse button
    • Identify and re-title unique ligands by option menu
    • Skip duplicate ligands option
  • Conformation generation section
    • Generate ligand conformers option
    • Target number of conformers text box
• Ligand Preparation tab
• Prepare ligand structures option and section
  • Generate possible states at target pH text boxes
  • Using options
  • Add Epik metal-binding states option
  • Steroisomers options
  • Retain at most N low-energy stereoisomers per ligand text box
  • Generate up to N low-energy 5- and 6-membered ring conformations text box
  • Enhance sampling of large rings using MacroModel option
  • Remove high-energy ionization/tautomer states
• Ligand Filtering tab
• Filter input ligands section
  • Only import ligands with Title values in subset file option
  • Subset file option menu and Browse button
• Filter prepared ligands section
  • Generate QikProp properties option
  • Prefilter by Lipinski's rule option
  • Skip ligands with reactive functional groups option
  • Generate LigFilter properties option
  • Retain only ligands matching criteria option and controls

Job toolbar

Status bar

Input tab

In this tab you specify the database, the files that contains the structures to be added to the database, how to identify ligands, whether to skip duplicate structures, and options for generating conformers.

Task section

In this section you specify the task and the database.

Choose task options

Select an option for the task: Create new database or Append to existing database.

Job will run on localhost option

Select this option if you plan to run the job on your local machine. This option determines which set of controls for specifying the location of the database is displayed. If this option is selected, the Specify the database location as an absolute path text box and Browse button is displayed; if not, the Specify the database location on the job host as an absolute path text box is displayed.

If you select this option, you must make sure that you choose localhost as the host in the Job Settings Dialog Box.

Specify the database location as an absolute path text box and Browse button

Specify the path to the database, either by entering it in the text box or by clicking Browse, navigating to the location and naming or selecting the database. The database path must exist on the file systems accessible to the local host, and should be an absolute path.

Specify the database location on the job host as an absolute path text box

Specify the path to the database on the job host, by entering it in the text box. The database path must exist on the file systems accessible to the host on which you plan to run the job, and should be an absolute path.

Ligands section

In this section you specify the source and handling of the ligands to be added to the database.

Use ligands from option menu

Choose the source of the ligands.

• Project Table (selected entries)—Use the entries that are currently selected in the Project Table.
• File—Use the structures from the specified file. When this option is selected, the Input structure file text box and Browse button are displayed.

Input structure file text box and Browse button

Specify the input structures. Enter a file name in the text box, or click Browse to navigate to the file.

If you want to specify multiple structure files with related names, you can use the wild card characters * and ? in the file name. These characters have their usual Unix file-matching meanings: ? matches a single character, and * matches zero or more characters.

To specify multiple structure files with unrelated names, you can create a text file that contains a list of structure file names, and specify this text file in the Input structure file text box, or navigate to it.

Identify and re-title unique ligands by option menu

Select the property to be used for the structure titles from this option menu. The title is used to associate structures that originate from the same compound (conformers, tautomers, ionization states). The property names are taken from the first structure in each file, and only those properties that exist in each file are presented. You should ensure that the property you choose exists for each structure in the file, not just the first.

Skip duplicate ligands option

When adding structures, check whether they are already in the database; if they are, skip them. The check is done by generating a unique SMILES string for the structures.

Conformation generation section

In this section, you select options for the generation of ligand conformers.

Generate ligand conformers option

Select this option to generate ligand conformers with ConfGen. If you deselect this option, it is assumed that the input structure file contains conformers, grouped together in the file. It is also assumed that the ligands are already prepared, so the controls in the Ligand Preparation tab are disabled.

Target number of conformers text box

Enter the target number of conformers to generate per structure in this text box. The default is 100.

Ligand Preparation tab

This tab contains controls for structure preparation, which is done with LigPrep. If your structures are already 3D structures in the appropriate ionization and tautomeric state, you can deselect the Prepare ligand structures option. If you deselected Generate ligand conformers in the Input tab, the controls are disabled, as it is assumed that the ligands are already prepared.

Prepare ligand structures option and section

Select this option if you want to prepare the ligand structures with LigPrep. The remaining controls in the section are activated when you select the option (which is selected by default).

Generate possible states at target pH text boxes

Generate ionization and tautomeric states that have significant probability in the given pH range. You must generate states in all ionization and tautomeric states that you want to use for searches, as the pharmacophore feature assignment does not automatically assign features for both neutral and ionized states, or for different tautomeric states, if only one of them is present. Enter the target pH and the range in the Generate states at target pH text boxes.

Using options

Choose whether to use Ionizer or Epik to generate ionization and tautomeric states. Epik is recommended (and the default), as it does a more thorough job.

Add Epik metal-binding states option

Add states suitable for binding to metals. These states are not usually present at around neutral pH.

Steroisomers options

Specify how to determine the stereochemistry of the structures:

• 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 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 structures— 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.

Retain at most N low-energy stereoisomers per ligand text box

Enter the maximum number of stereoisomers to be retained by LigPrep in this text box. LigPrep generates up to 32 stereoisomers, which are then filtered to retain those with the lowest energies. Note that LigPrep selects starting chiralities based on the chemistry of naturally occurring steroids, fused rings and peptides.

Generate up to N low-energy 5- and 6-membered ring conformations text box

Enter the maximum number of ring conformations for 5- and 6-membered rings to be generated by LigPrep in this text box.

Enhance sampling of large rings using MacroModel option

Sample conformations of 7-membered and larger rings with MacroModel after structure preparation. These ring conformations are not sampled by LigPrep.

Remove high-energy ionization/tautomer states

Select this option to remove ionization and tautomeric states that have high energies. These are states that are likely to have low populations at the prevailing conditions.

Ligand Filtering tab

In this tab you can filter out structures that do not meet specified criteria.

Filter input ligands section

Filter the input structures so that only those containing specified values of the Title property are added to the database. The values are specified in a file, one value per line.

Only import ligands with Title values in subset file option

Select this option to restrict the import of ligands to those with values of the Title that are specified in a file.

Subset file option menu and Browse button

Enter the file name in the text box, or click Browse and navigate to the file.

Filter prepared ligands section

Filter the ligands after preparation by one or more of the criteria given in this section.

Generate QikProp properties option

Select this option to run QikProp after the structure preparation is done. You must run QikProp if you want to prefilter the structures using the Lipinski Rule, or use QikProp properties for custom filtering. If your structure files already have QikProp properties, you do not need to run QikProp again.

Prefilter by Lipinski's rule option

Prefilter the structures using Lipinski's Rule of 5 before addition to the database. Structures that do not satisfy this rule are not added. This option requires QikProp properties. If the input structure files do not have QikProp properties, select Run QikProp in this tab.

Skip ligands with reactive functional groups option

Prefilter the ligands by removing those that have reactive groups. The filtering is done by ligfilter with a predefined set of reactive groups, which are:

Acyl halides Sulfonyl halides Sulfinyl halides Sulfenyl halides Alkyl halides without fluorine Anhydrides Perhalomethylketones Aldehydes Formates Peroxides

R-S-O-R Isothiocyanates Isocyanates Phosphinyl halides Phosphonyl halides Alkali metals Alkaline-earth metals Lanthanide series metals Actinide series metals Transition metals

Other metals Toxic nonmetals Noble gases Carbodiimides Silyl enol ethers Nitroalkanes Phosphines Alkyl sulfonates Epoxides Azides

Diazonium compounds Isonitriles Halopyrimidines 1,2-Dicarbonyls Michael acceptors Beta-heterosubstituted carbonyls Diazo compounds R-N-S-R Disulfides

Generate LigFilter properties option and controls

Retain only ligands matching criteria option

Prefilter the ligands using ligfilter, retaining only those that match the criteria specified in a given filter file. To set up a new filter file, click Create. This button opens the Ligand Filtering dialog box.

To read an existing filter, click Browse and navigate to the file.

Select Before preparation or After preparation to determine at what point the criteria are applied.

Job toolbar

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

The Job Settings button opens the Create Phase Database - 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.