Shape Screening Panel

In this panel you can set up and run a search for molecules that have similar shape to a shape query, which is either a template molecule or a set of spheres of defined radius and coordinates.

To open this panel, do one of the following:

  • Click the Tasks button and browse to Ligand-Based Virtual Screening → Shape Screening
  • Click the Tasks button and browse to Shape Screening → Shape Screening
  • Overview
  • Using
  • Features
  • Additional Resources

Overview of Shape Screening

The Shape Screening program can be used to screen one or more files or a Phase database against a shape query. Each conformer from a given molecule is aligned to the query in various ways, and a similarity is computed based on overlapping hard-sphere volumes. The conformer and alignment yielding the highest similarity for each molecule is written to a Maestro file, along with the similarity property r_phase_Shape_Sim, which appears in the Project Table as Shape Sim.

The shape query can be a single template molecule, a Phase pharmacophore hypothesis, or a set of three or more spheres. The last of these forms provides a high degree of flexibility in designing the shape. For each molecule searched, Shape Screening returns an aligned structure that provides the best overlap with the shape query. If you are searching a set of homologous structures and the shape query is a member of the same series, then Shape Screening should return the most sensible alignment among all those available. If you are searching against structures that are not necessarily related to the shape query, Shape Screening should return something that looks most like the query in an overall sense.

The shape search can treat all atoms as equivalent, or it can incorporate information on atom types as part of the search. Searching on atom types favors alignments that superimpose atoms of the same type. There are three possibilities for atom typing in a shape search: use of MacroModel types, typing by element, and use of Phase QSAR types. MacroModel atom types will impose the most stringent conditions on the matching, and Phase QSAR types will impose the most general conditions.

As an alternative, the shape search can treat each structure as a collection of pharmacophore sites, whose locations are assigned by applying Phase pharmacophore feature definitions. Overlapping volumes are computed only between sites of the same type.

Volume scoring as part of a search for matches to a hypothesis also uses molecular shape, but there are some important differences between volume scoring in a search for matches and shape-based queries. In the search for matches, the molecules are aligned to the hypothesis, and the volume overlap is then computed on the basis of that alignment. The molecular shape alignment might not be optimal in this case. Shape queries investigate a much greater variety of alignments than a typical search for matches to a hypothesis, and compute volume overlaps that are closer to optimal. A second difference is in the algorithm used to evaluate the volume scores in the search for matches on the one hand, and the shape similarities on the other. However, the shape similarities are a form of volume scoring, and this term is used below for the shape similarities.

Using the Shape Screening Panel

To set up a search by shape:

  1. Choose the source of the shape from the Use shape query from option menu.

    If you chose File, enter the file name in the Shape query file text box or click Browse to browse to the file.

  2. Choose the processor type for the screen, from CPU or GPU.

  3. Choose the source of the structures to be screened from the Screen structures in option menu.

    For CPU screening, if you chose File or Phase database (local), enter the file name or Phase database name in the text box, or click Browse to browse to the file or database; if you chose Phase database (remote), enter the full path to the remote Phase database in the text box.

    For GPU screening, if you chose Shape data file (local), enter the data file names in the text box, or click Browse to browse to the data files; if you chose Shape data file (remote), enter the full path to the remote data files in the text box.

  4. For CPU screening, if the structures to be searched do not include conformer sets, you can choose to generate conformers, by clicking Screening Settings and selecting Generate conformers in the Shape Screening Settings Dialog Box.

    If you want to limit the number of conformers generated per input structure, enter a value in the Target number of conformers text box.

  5. For CPU screening, choose an atom type for use in volume scoring. Volume overlaps are only calculated for atoms of the same type.

  6. Click the Job Settings button,

    set the job parameters in the Job Settings Dialog Box, and click Run to run the job. You can distribute CPU searches over multiple processors if you are searching a database or generating conformers.

If you want control over other aspects of the screening run, click Screening Settings and make the settings in the Shape Screening Settings Dialog Box.

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 shape_screen Command Help or shape_screen_gpu Command Help.

Shape Screening Panel Features

Shape query controls

These controls allow you to choose the shape query.

Use shape query from option menu

Choose the structure source for the shape query.

  • Workspace (included entries)—Use the entries that are currently included in the Workspace, treated as separate structures.
  • 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, Phase hypotheses (.phypo), and Phase included volumes (.ivol).

If you selected Workspace and there are multiple entries included in the Workspace, a query is constructed for each entry. However, if you have a Phase hypothesis in the Workspace, it is used and other molecules are ignored; it must also be the only hypothesis in the Workspace.

Open Project Table button

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

Shape query file 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. The allowed file types are: Maestro.

Run screen on options

Choose the hardware type to run the screen on. The choice affects the options that are available for screening, and the choice of hosts on which you can run the job, which you select in the Job Settings Dialog Box. For more information on CPU and GPU usage in shape screening, see The shape_screen and shape_screen_gpu Commands

  • GPU—run the screen on a graphics processor. You must have a host with graphics cards for running jobs available for this choice. Screening on a GPU requires creation of a shape data file from a set of ligands prior to screening, using the Create Shape Data File Panel. The shape data file may take some time to load onto the GPU; after that, the screening is run on the GPU with high efficiency.

  • CPU—run the screen on a regular processor.

Structures for screening controls

These controls allow you to choose the set of molecules to be screened.

Screen structures in option menu

Choose the structure source for screening. For CPU screening, the following options are available:

  • File—Use the specified file. When this option is selected, the File name text box and Browse button are displayed. Click Browse and navigate to the file you want to use. The file name is displayed in the text box when you click Open in the file selector. You can also enter the file name in the text box. The allowed file types are: Maestro, SD, and SMILES.

  • Phase Database (local)—Use the structures in the specified locally installed Phase database. When this option is selected, the Local database text box and Browse button are displayed. Click Browse and navigate to the database (.phdb) you want to use. The database name is displayed in the text box when you click Open in the file selector. You can also enter the database name in the text box.

  • Phase Database (remote)—Use the structures in the specified remotely installed Phase database, i.e. a database that is accessible to the host on which you run the job, but not necessarily to the local host. When this option is selected, the Local database text box is displayed. You must enter the full path to the database (.phdb) on the execution host in the text box.

  • Project Table (selected entries)—Use the entries that are currently selected in the Project Table.

For GPU screening, the following options are available:

  • Shape data file (local)—Use the structures in the specified local shape data files. When this option is selected, the Local shape data files text box and Browse button are displayed. Click Browse and navigate to the shape data files (.bin) you want to use. The shape data file names are displayed in the text box when you click Open in the file selector. You can also enter the shape data file names in the text box. To create a shape data file, use the Create Shape Data File Panel.

  • Shape data file (remote)—Use the structures in the specified remotely installed shape data files, i.e. shape data files that are accessible to the host on which you run the job, but not necessarily to the local host. When this option is selected, the Remote shape data files text box is displayed. You must enter the full paths to the shape data files (.bin) on the execution host in the text box. To create a shape data file, use the Create Shape Data File Panel.

File name, Local database or Local shape data file text box and Browse button

If you chose Phase database (local), Shape data file (local), or File from the Screen structures in option menu, enter the database or file name in this text box, or click Browse and navigate to the database or file. The name of the database or file you selected is displayed in the text box.

Remote database text box

If you chose Phase database (remote) from the Screen structures in option menu, enter the full path to the database on the intended execution host in this text box.

Volume scoring options

Choose the type of object that is used for volume scoring. These options are not available for GPU screening. When the query is a Phase hypothesis, the Typed pharmacophore option is selected and the others are disabled.

  • Typed pharmacophore—Treat each structure as a collection of pharmacophore sites, whose locations are assigned by applying Phase pharmacophore feature definitions. Overlapping volumes are computed only between sites of the same feature type. Each site is represented by a sphere of radius 2 Å.
  • Typed atoms—Treat each structure as a collection of atoms, whose volumes are defined by their van der Waals radii. Overlapping volumes are computed only between atoms of the same type. The MacroModel atom typing scheme is used—see MacroModel Atom Types for information.
  • Untyped atoms—Treat each structure as a collection of atoms, whose volumes are defined by their van der Waals radii. Overlapping volumes are not restricted by atom type.
Screening Settings button

Open the Shape Screening Settings Dialog Box, in which you can make other settings for the screening process.

Job toolbar

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

The Job Settings button opens the Shape Screening - 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

Related Topics