FEP+ Hot Atoms Dialog Box

Set options for hot atoms in FEP calculations, for existing edges with no predicted ΔG and for any subsequently added edges.

To open this dialog box, click Hot Atoms in the Map Tab of the FEP+ panel.

  • Using
  • Features
  • Additional Resources

Using the FEP+ Hot Atoms Dialog Box

The default hot atom selection for ligands is done in steps, as follows:

  1. The perturbed atoms are grouped into sets in which the atoms are contiguously connected. These can be considered as "fragments". The hot atom set is at this stage considered to be empty.
  2. Each fragment is considered in turn, from the one with the fewest atoms to the one with the most.
  3. The bonds from the rest of the ligand to the fragment are examined:
    1. If a bond is rotatable, the atom that is not in the fragment is added to it, with its immediate terminal attachments (e.g. –H, –F, =O). Atoms from the fragment that are not already in the hot atom set are added to it.
    2. If the bond attaches the set to a ring, the ring is added to the fragment and a search is made for rotatable bonds attached to the ring (which may be a fused ring system). The atoms in the enlarged fragment are added to the hot atom set if they are not already in it.
    3. If the bond is not rotatable, the atoms are added to the fragment but not to the hot atom set . This would happen for a hydrogen or a methyl group, for example.
  4. The process is repeated (in the same order of fragments as before, not by the new size) to find rotatable bonds for the enlarged fragments.
  5. The process stops when the next addition would exceed the maximum number of heavy atoms, which is 24 if the hot region does not contain a ring, or 30 if the hot region contains a ring.

This may mean that some atoms that are part of the perturbation do not end up in the hot region, but these are likely in groups that would contribute little to conformational sampling via the REST method.

If your choice of the number of atoms exceeds the limits, you should consider either reducing the number of atoms, or increasing the number of lambda windows, to ensure effective sampling. Increasing the number of lambda windows can be done from the FEP+ Advanced Options Dialog Box or the command line (see fep_plus Command Help). For background on the hot region, see FEP/REST Enhanced Sampling Method.

FEP+ Hot Atoms Dialog Box Features

Ligand (solvent leg) option menu

Choose the hot region for the ligand in the solvent. The default for the hot region is in the Using section. If your choice exceeds the limit, a warning is posted. However, the job still runs with these hot regions but might not produce good results.

  • Default—use the default ligand atoms for the hot region in the solvent.

  • All—use all ligand atoms for the hot region in the solvent. If Default is selected in the Ligand (complex leg) option menu, this option provides more conformational sampling of the entire ligand when it is in the solvent. If All is selected in the Ligand (complex leg) option menu, this option provides conformational sampling of the entire ligand rather than just in the vicinity of the perturbation.

  • None—Do not use any ligand atoms for the hot region in the solvent.

Ligand (complex leg) option menu

Choose the hot region for the ligand in the complex. The default for the hot region is in the Using section. If your choice exceeds the limit, a warning is posted. However, the job still runs with these hot regions but might not produce good results.

  • Default—use the default ligand atoms for the hot region in the complex.

  • All—use all ligand atoms for the hot region in the complex.

  • None—Do not use any ligand atoms for the hot region in the solvent.

Receptor hot atom ASL text box

ASL expression for the receptor atoms to include in the hot region. You can enter an ASL expression directly, or you can pick residues or atoms in the Workspace. If you start typing in the text box, the Pick option is turned off. If you pick atoms or residues in the Workspace, the ASL expression is replaced. To clear the expression, click the X button at the end of the text box.

The maximum number of heavy atoms you can pick for the hot region is 40.

Water molecules are excluded from any ASL expression entered, as these destabilize the simulation.

Pick option and menu

Pick receptor residues or atoms in the Workspace that you want to include in the hot region. The menu offers the choice of Atoms or Residues for picking. When you pick atoms, picking an unselected atom selects it, and picking a selected atom deselects it. You can drag over atoms to add them to the selection. The ASL expression in the Receptor hot atom ASL text box is replaced by the expression for what you pick, adding to it until you stop picking. After picking, you can manually edit the ASL expression. The number of receptor atoms is displayed below.

Only side chains option

Only include the side chains of the picked residues in the receptor hot atom ASL. When unchecked, the entire residues are included in the ASL.

Reset button

Reset the settings in the dialog box to their default values.

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