Ligand Alignment - Advanced Options Dialog Box

Ligand Alignment - Advanced Options Dialog Box Features

The options present depend on choices made in the Ligand Alignment Panel: whether the reference structure is chosen from the list or selected automatically, whether a common scaffold is defined for constraint. For each option that is conditionally available, the option choices from the parent panel are listed.

• Sampling method options
• Maximum number of conformers text box
• Run energy minimization on each conformer option
• Refine with additional conformers option
• Volume scoring options
• Customize atom weights option and section
  • Default atom weight option menu and Apply button
  • Get from Selection button
  • Custom weight option menu and Apply button
  • Weights table
• Nonbonded close contact distance text box
• Reset button

Sampling method options

Choose an option for the conformational sampling. Rapid is faster but generates conformers of lower quality; Thorough is slower but generates conformers of higher quality (for example, for complex saturated fused ring systems).

Maximum number of conformers text box

Enter the maximum number of conformers per input molecule to be generated in this text box. The default is 100 for alignments with a reference of unknown conformation (flex_align Command Help). For other alignment types the default is 1000.

Run energy minimization on each conformer option

Run a force-field minimization of the energy of each conformer. This option dominates the time taken for conformer generation, if it is used.

This option is available when the reference is chosen automatically, or when the Largest common Bemis-Murkco scaffold or the SMARTS option is used to constrain the common substructure (Constrain common substructure) with a user-specified reference.

Refine with additional conformers option

Refine alignments by generating additional conformers with core atoms held fixed, and identifying conformers that increase the average in-place shape similarity between all pairs of ligands.

This option is available when the reference conformation is sampled (Sample reference ligand) for a user-specified reference.

Volume scoring options

Choose the method for typing atoms when calculating the volume score for shape similarity. The default is Typed atoms.

• 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 Element atom typing scheme is used—atoms of each element are considered to be the same type.
• 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.

These options are only available when the reference conformation is sampled (Sample reference ligand) or when the MCS option is used to constrain the common substructure (Constrain common substructure) with a user-specified reference. The Typed pharmacophore option is not available with the MCS option for a user-specified reference.

Customize atom weights option and section

Customize the weights used for contributions from individual atoms when evaluating the volume score for typed or untyped atoms. This is useful for emphasizing or de-emphasizing chosen parts of the reference structure in the score. These options are only available if the reference conformation is sampled, and the scoring is done on typed or untyped atoms.

Default atom weight option menu and Apply button

Choose the default value for the weights from the option menu. The values are between 0.0 and 2.0; the default is 1.0. Click Apply to set the default weights to the chosen default weight).

Get Workspace Selection button

Select the rows in the table for the atoms that are selected in the Workspace (reference) structure.

Custom weight option menu and Apply button

Set the weights for the atoms in the selected rows of the weights table to the chosen value, when Apply is clicked. The default is 1.0.

Weights table

This table lists the atoms in the Workspace structure by atom number and element (and PDB name if it exists), and the weight to use for each atom. You can select multiple rows to set the weight value, using the tools above the table. The atoms in the selected rows are highlighted in the Workspace. The weights are applied in the alignment, but are not stored.

Nonbonded close contact distance text box

When using core snapping for alignment, reject a snapped structure if the snapping places two nonbonded atoms closer than this distance (a "close contact"). If every mapping of the core results in the creation of a close contact, use flexible least-squares alignment instead of core snapping. A value of 0 disables close contact detection.

This option is not available when the reference conformation is sampled (Sample reference ligand) for a user-defined reference.

Reset button

Reset the dialog box to its default settings, clearing all data.