Settings - Advanced Settings Dialog Box DEPRECATED

Settings - Advanced Settings Dialog Box Features

• Conformer generation section
• Selection of initial poses section
  • Keep n initial poses per ligand for the initial phase of docking text box
  • Scoring window for keeping initial poses text box
  • Keep best m poses per ligand for energy minimization text box
  • Use expanded sampling option
• Energy minimization section
  • Distance-dependent dielectric constant text box
  • Maximum number of minimization steps text box
• Count aromatic H and halogen H-bonds section
  • Include aromatic H as donors option
  • Partial charge cutoff text box
  • Include halogens as options

Conformer generation section

This section contains settings related to the generation of conformers of each ligand.

Energy window for ring sampling text box

The threshold for keeping or discarding ring conformations can be set in this text box. Ring conformations are discarded if their energies are higher than that of the lowest conformation by more than the amount specified.

Canonicalize 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.

The poses obtained in docking can depend on details of the input structure. Sometimes this is useful, to obtain a wider range of poses, but it can also prevent comparisons between docking runs that should not depend on the detailed structure of the input ligands.

Use enhanced sampling option

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

Enhance conformational sampling by N times 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.

Selection of initial poses section

The options in this section control the way poses pass through the filters for the initial geometric and complementarity fit between the ligand and receptor molecules. The grids for this stage contain values of a scoring function representing how favorable or unfavorable it would be to place ligand atoms of given general types in given elementary cubes of the grid. These grids have a constant spacing of 1 Å. The rough score for a given pose (position and orientation) of the ligand relative to the receptor is simply the sum of the appropriate grid scores for each of its atoms. By analogy with energy, favorable scores are negative, and the lower (more negative) the better.

The initial rough scoring is done on a coarse grid, on which the possible positions for placing the ligand center are separated by 2 Å, twice the elementary cube spacing, in X, Y, and Z. The refinement step rescores the successful rough-score poses after the particular rigid translational repositioning of -1, 0, or +1 Å in X, Y, and Z, which gives the best possible score. This procedure effectively doubles the resolution of the scoring screen.

Keepninitial poses per ligand for the initial phase of docking

This text box sets the maximum number of poses per ligand to pass to the grid refinement calculation. The default setting depends on the type of docking specified and whether Glide constraints have been applied:

• 5000 poses for flexible docking jobs in general.
• 500 poses for flexible docking jobs to which Glide constraints are applied.
• 1000 poses for rigid docking jobs (Glide constraints do not change this value.)
• 100000 poses for peptide docking jobs

You can change the default by entering any integer greater than zero.

Scoring window for keeping initial poses

This text box sets the rough-score cutoff for keeping initial poses, relative to the best rough score found so far. The value must be positive. The default window is 100.0 kcal/mol, meaning that to survive, the rough score of a pose must be within 100.0 kcal/mol of the best pose. Using the default window, for example, if the best pose found so far has a score of -60.0 kcal/mol, poses with a score more positive than 40.0 kcal/mol are rejected. You can change this value from the default to any number greater than zero.

Keep bestm poses per ligand for energy minimization text box

This value allows at most the number of poses specified per ligand to be energy-minimized on the receptor grid. The default setting depends on the type of docking specified:

• 400 poses for flexible SP docking jobs, 800 poses for flexible XP docking jobs.
• 40 poses for flexible docking jobs to which Glide constraints are applied.
• 100 poses for rigid docking jobs (Glide Constraints do not change this value.)
• 1000 poses for peptide docking jobs.

The range for this value for SP docking is 1 to n, where n is the value in the Keepninitial poses per ligand for the initial phase of docking text box, except that for XP docking, the allowed range is 800 to 1000.

Use expanded sampling option

Expand the sampling in the rough scoring stage by bypassing the elimination of initial poses based on the rough score. This option passes many more poses to the later stages, which is especially useful for fragment docking to ensure that good poses are found.

Energy minimization section

This stage of the docking algorithm evaluates and minimizes poses that are passed through the Selection of initial poses scoring phase.

Distance-dependent dielectric constant

Glide uses a distance-dependent dielectric model in which the effective dielectric "constant" is the supplied constant multiplied by the distance between the interacting pair of atoms. The default setting is 2.0, and Glide's sampling algorithms are optimized for this value. Although this text box allows you to set the dielectric constant to any real value greater than or equal to 1.0, changing this setting is not recommended. This relatively strong dielectric is sometimes needed to “hold” a hydrogen bond in the energy-grid optimization phase of the algorithm.

Maximum number of minimization steps

Set the maximum number of minimization steps that are used by the conjugate gradient minimization algorithm. The default number of steps is 100 but you are allowed to choose any value greater than or equal to 0. A "minimization" of 0 steps does a single-point energy calculation on each pose that survives rough-score screening, or on the single initial pose if no screening was done.

Count aromatic H and halogen H-bonds section

These settings control whether aromatic hydrogens are considered to form hydrogen bonds, whether halogens can form hydrogen bonds as an acceptor or weak bonds with electronegative atoms (like oxygen) as a donor. 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.

Include aromatic H as donors option

Select this option to include aromatic ligand hydrogen atoms as donors during docking. You can set a cutoff for the partial charge, to filter out hydrogens that have small partial charges, in the Partial charge cutoff text box.

Partial charge cutoff 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.

Include halogens as options

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

• acceptors—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).