Ligand Docking - Advanced Settings Dialog Box

Ligand Docking - Advanced Settings Dialog Box Features

• Conformer Generation section
  • Energy window for ring sampling text box
  • Clean up input conformation option
  • Generate additional variations for sampling option
    • Enhance sampling by a factor of text box
• Aromatic H and Halogen H-bonds section
  • Include aromatic H as donors option
    • Partial charge must exceed text box
  • Include halogens as option and settings
• Pose Filtering section
  • Coulomb + vdW energies (combined) cannot exceed text box
  • Discard duplicate poses settings
    • Do not discard if hydroxyl/thiol torsion angles differ by at least option
  • Preserve archive of sub-job poses option
• Energy Adjustments section
  • Reward intramolecular hydrogen bonds option
  • Enhance planarity of conjugated pi groups option
  • Post-docking strain corrections
    • Strain threshold text box
    • Scaling factor text box

Conformer Generation section

This section contains settings related to the generation of conformers of each ligand. This section is hidden when Ligand sampling is set to None, and is disabled for HTVS precision.

Energy window for ring sampling text box

The threshold for keeping or discarding ring conformations. Ring conformations are discarded if their energies are higher than that of the lowest conformation by more than the amount specified. The default is 2.5 kcal/mol.

Clean up input conformation option

Ensure that the same starting conformation is always used for a given ligand, regardless of the input conformation or orientation, so that the output poses do not depend on details of the input structure. This is done by generating a new set of coordinates for the ligand based only on the connectivity and stereochemistry.

Generate additional variations for sampling option

Enhance the sampling of conformational space by adding variations on the input structure to the conformational search.

Enhance sampling by a factor of text box

Enhance the conformational sampling by the factor specified in the text box. This is done by generating variations on the input structure, and using these as seed structures along with the input structure for conformational sampling. The default factor is 2. This text box is only available when Generate additional variations for sampling is selected.

Aromatic H and Halogen H-bonds section

These settings control whether aromatic hydrogens are considered to form hydrogen bonds, and whether halogens can form hydrogen bonds as acceptors or weak bonds with electronegative atoms (like oxygen) as donors. These bonds are treated like other hydrogen bonds: they are included in the rough scoring, in the final scoring function, and are considered for hydrogen-bond constraints. This section is disabled for HTVS precision.

Include aromatic H as donors option

Select this option to include aromatic ligand hydrogen atoms as donors during docking.

Partial charge must exceed text box

To be considered as a donor, the partial charge on an aromatic hydrogen must be greater than the value given in this text box. Only available when Include aromatic H as donors is selected.

Include halogens as option and settings

Select this option to include nonbonded interactions with ligand halogens. You can choose one of two possibilities for halogen interactions:

• Acceptors (default) — Treat halogens as acceptors of hydrogen bonds.
• Donors — Treat halogens as donors of nonbonded interactions with electronegative atoms, such as oxygen. This effect originates in the positive potential on the halogen in line with the bond axis (sigma hole).

Pose Filtering section

Coulomb + vdW energies (combined) cannot exceed text box

Reject poses with Coulomb-van der Waals energy scores greater than the specified cutoff (in kcal/mol).

Discard duplicate poses settings

A pose is considered a duplicate if both of the following conditions are true:

• RMSD of heavy atoms is less than the specified value (default 0.5 Å)
• Maximum deviation is less than the specified value (default 1.3 Å)

This section is hidden when Ligand sampling is set to None.

Do not discard if hydroxyl/thiol torsion angles differ by at least option and text box

Select this option and specify the minimum torsion angle difference (in degrees) between hydroxyl/thiol groups to prevent discarding poses that differ only in these torsion angles. The default is 40 degrees. This option is selected by default.

Preserve archive of sub-job poses option

Select this option to keep an archive of the poses generated by individual sub-jobs, in addition to the merged output. This option is selected by default.

Energy Adjustments section

Reward intramolecular hydrogen bonds option

Select this option to reward intramolecular hydrogen bonds in the ligand during docking.

Enhance planarity of conjugated pi groups option

Select this option to apply a penalty for nonplanarity in conjugated pi groups, such as biphenyl.

Post-docking strain corrections

Strain correction values over a threshold are scaled and added to the GlideScore. These controls are enabled when Include strain correction in post-docking score is selected in the Docking options popup.

Strain threshold text box

Set the strain energy threshold in kcal/mol. Strain corrections are only applied if the computed strain exceeds this threshold. The default is 4.0 kcal/mol.

Scaling factor text box

Set the factor by which the excess strain energy above the threshold is scaled before adding it to the GlideScore. The default is 0.25.