FEP+ Panel — Groups Tab

This tab is only present if the fmp file is from a small molecule absolute binding calculation.

This tab shows groups of protomers (protonation states), tautomers, or conformers of a given compound, for which binding free energies can be calculated taking account of the populations of these species in solution. The structures belonging to each compound are automatically detected.

Protonation and deprotonation events are fast and ubiquitous. What may be thought of as a single ligand may in fact be an ensemble of rapidly interconverting tautomers and protomers. The tautomers and protomers of ligands in FEP+ can be accounted for by adding every state as a separate node in the perturbation map. If the populations or pKa values of the protomers or tautomers in water are known, the complex populations or pKa values can be calculated by FEP+ using the method described by de Oliveira et al. [9].

Likewise, if there is uncertainty about which conformation of a ligand binds to a protein, or if a ligand can bind in multiple different poses, each conformation can be added as a separate node in the perturbation map. After the FEP+ calculation has finished, the effect of the conformations can be automatically accounted for on the assumption that the ligand cannot switch between the different conformations in the complex, but can and readily does so in the solvent.

  • Features
  • Additional Resources

Groups Tab Features

Use pH text box

Use the specified pH to calculate the populations of protomers in solution.

Auto-populate

Use Epik to calculate the pKa values for a given pH and populate the table.

Groups table

This table shows the groups that were identified and allows you to edit the data to specify the populations or pKa values for the compound represented by the group. Hover over the row and click the edit (pencil) icon, or double-click the row to open the Grouping Dialog Box for editing the data for a compound (group).

Titles This column lists the structures in the group (or compound) by title as a comma-separated list.
# This column shows the number of structures in the group.
Solvent Population This column shows the populations of each structure in solution, separated by slashes. The populations are specified either via the pKa (for protomer pairs) or directly (for tautomers). Conformer populations in solution are assumed to be equal.
Solvent pKa This column shows the pKa for the compound (as applicable).
Complex Population This column shows the populations of each structure in the complex, separated by slashes. The populations are derived from the values input for the compound in the solvent.
Complex pKa This column shows the pKa for the structure in the complex (as applicable).
Clear All link

Clear the population and pKa data from the table.

Show group information in options

  • Table only—Only show group corrections in the Groups table. This allows you to change the map after applying group corrections to the free energy.

  • Map and other data displays—Apply corrections based on the populations of the groups to the free energies. The group free energy value is applied to all structures in the group. You cannot change the map while the group free energies are in effect.

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