Excluded Volumes from Inactives and Actives Dialog Box

Create excluded volumes for a Phase hypothesis in regions occupied by atoms in a set of inactives that do not overlap with atoms in a set of actives. The actives and inactives must be prealigned to the hypothesis for which the excluded volumes are created.

To open this dialog box, click Inactives and Actives in the Manage Excluded Volumes panel.

  • Using
  • Features
  • Additional Resources

Using the Excluded Volumes from Inactives and Actives Dialog Box

The basis of this procedure for generating excluded volumes is that any region of space in which inactives have atoms but actives do not corresponds to a region that is not favored for activity. These are considered to be "clashes". The reason might be that the region has a receptor side chain that has to be moved out of the way, or that there are solvent molecules in this region that incur a penalty for replacement, or that there are unfavorable interactions with the receptor in this region. There are, of course, other reasons why molecules are inactive (or poor binders): for example, they might be missing a critical pharmacophore feature. When choosing the inactives, therefore, it is a good idea to choose those inactives that match all features in the hypothesis. The choice of actives should be as structurally diverse as possible, to avoid placing excluded volumes in regions that have no effect on activity (such as non-critical solvent regions).

You must ensure that the actives and inactives are aligned to the pharmacophore hypothesis. You can use the Phase Ligand Screening Panel with the actives and the inactives, and use the hit file for the aligned ligands, or use the phase_find_matches utility.

If you are adding excluded volumes from the Develop Common Pharmacophore Hypotheses panel, you must export the actives and the inactives from the Alignments table. You can right-click and choose Export Alignments to Project Table. You can then select the desired actives in the Project Table, and export them, and likewise with the desired inactives. You should consider actives and inactives that are not part of the pharm set, in the light of the discussion above.

Excluded Volumes from Inactives and Actives Dialog Box Features

Actives file text box and Browse button

Enter the name of the file that contains the active compounds in the text box, or click Browse and navigate to the file. All structures in this file are used as actives.

Inactives file text box and Browse button

Enter the name of the file that contains the inactive compounds in the text box, or click Browse and navigate to the file. All structures in this file are used as inactives.

Minimum number of inactives that must experience a clash text box

Specify the minimum number of inactives that must have atoms in a non-active region for an excluded volume to be placed in that region.

Minimum distance between active surface and excluded volumes text box

Specify the minimum distance between the van der Waals surface of any active ligand and the surface of an excluded volume sphere, in angstroms. This buffer distance can be considered to simulate receptor flexibility.

Excluded volume sphere radii text box

Specify the radius that is to be used for the excluded volume spheres. Using a larger radius produces less spheres, but results in a less well-defined shape for the excluded region.

Create Excluded Volumes button

Click this button to run the application that creates the excluded volumes and close the dialog box. When the application finishes, the excluded volumes are added to the table in the Exlcuded Volumes dialog box.

Related Topics