FEP+ Panel — Overview Tab

This tab gives an overview of the ligands or protein mutants, and the results of the FEP+ calculations when they are done.

  • Features
  • Additional Resources

Overview Tab Features

The Overview tab contains a table with information for each ligand or protein mutation for affinity FEP, or compound for solubility FEP. The columns are described below. Columns can be shown or hidden by right-clicking in the column heading row.

You can resize all the rows by dragging the border of any row in the gray column to the far left. A resize arrow appears when you pause the pointer over the border. When the row height is below a threshold, the structure changes to a SMARTS string. Reducing the row size also changes the Estimated property display to fit, removing the scale markers and leaving only the markers for the experimental and predicted values when the row height is below a threshold.

The binding affinity can be reported as an affinity (ΔG), a Ki value or a pKi value. You can change between these three by clicking the Units button on the toolbar and choosing the desired quantity to report. The Ki and pKi values are only available if the map has experimental data; if there is no experimental data, the predictions are displayed as affinities and can't be changed to Ki or pKi.

# Ligand number: index of the ligand in the order in which it was imported.
Ligand or Protein or Compound Title of the ligand, compound, or the protein for protein mutation FEP.
Quality

Symbol indicating the quality of the ligand structure and conformation, and the force fields used for the ligand. A warning symbol is shown if a ligand has steric clashes with the protein or crystal waters, is not docked into the receptor, has missing atoms (in a covalent complex), or does not have explicit torsional parameters in the force field. It is expected that the force-field builder is used to generate these torsional parameters, to ensure the quality of the FEP+ results.
If there is a steric clash, you may need to adjust the ligand conformation, or remove a clashing water if it is buried. Although the minimization step will help alleviate clashes, it's better to ensure that severe clashes with the protein or buried water are resolved prior to the calculation. If the ligand is not docked, you will need to run a docking job first (or otherwise position the ligand correctly in the binding pocket).
For fragment linking, an error is shown if both ligands are charged, as the hydration free energy cannot be reliably calculated. You should ensure that there is at most one charged ligand.
Not present for protein mutation FEP.
Predicted Binding Plot

Graphical representation of the estimated affinity for the ligand, or the dissolution free energy for solubility, shown as a range based on the predicted error. The range is indicated by two vertical lines joined by a horizontal line, in black. If an experimental value is available, it is shown as a blue vertical line. If an experimental error is also available, the range is indicated by two vertical lines joined by a horizontal line, all blue. If the experimental value is an inequality, the range is indicated by a blue horizontal line extending from the vertical line for the value to the appropriate side of the plot. If experimental values are not available, the column shows N/A rather than a plot. The heading changes when you click the Units button and choose a different quantity to display. You can resize the column by dragging the right border of the heading.
Pred. property

Predicted affinity value or dissolution free energy. Depending on the quantity represented, this column also shows the predicted error in pKi or ΔG, or the predicted error factor for the Ki value. Multiplying and dividing the Ki value by this factor gives the error bounds. If the predicted value is N/A, clicking on the adjacent information icon gives an explanation of why the value is missing.

Clicking the carat next to the column name opens a menu for sorting by value or error. The heading changes when you click the Units button and choose a different quantity to display. You can double-click in the cell to edit the value and error on both sides of the "±" indicator (as long as the values are valid numbers).

See FEP+ Methodology and linked topics for a full description of the prediction methods, and particularly Conversion of ΔΔG Values to ΔG Values.See Bennett Acceptance Ratio Method and Error Estimates, FEP Cycle Closure Method and Error Estimates, and Conversion of ΔΔG Values to ΔG Values for information on the error estimation.
Exp. property

Experimental property free energy value, which can be affinity or solubility depending on the simulation. Any ligand whose binding affinity or solubility free energy you enter is favored in the construction of the graph, by adding a further bias to the similarity. The property is also used in the analysis of the FEP results. To add experimental data, click the Affinity button menu and select Experimental Data. Once you have added experimental data, you can edit individual cells to set or change the values. For binding affinity, the value is preceded by a > or a < sign if the ligand has been designated as Top of assay or Bottom of assay (values outside the assay range). To clear all experimental data, right-click on the column heading and choose Clear All.

Depending on the quantity represented, this column shows the predicted error in pKi or ΔG, or the predicted error factor for the Ki value. Multiplying and dividing the Ki value by this factor gives the error bounds. You can double-click in the cell to edit the value (except if the units are Ki) and error on both sides of the "±" indicator (as long as the values are valid numbers). To clear all experimental error data, right-click on the column heading and choose Clear All. Additionally, right-clicking on the column displays the option to sort by either value or error.

The heading changes when you click the Units button and choose a different quantity to display.
Structure 2D structure of the ligand. This column can be sorted by the SMILES string for the structure, by clicking on the heading. Sorting is useful for identifying non-unique (duplicate) ligands. You can resize the column by dragging the right border of the heading. Not present for protein mutation FEP.
# of Edges Number of edges that connect ligand to other ligands. This column is not shown by default. Not present for absolute binding and solubility FEP.
Submap # The index of the submap to which the ligand belongs. Sorting by this column is useful to identify submaps and disconnected nodes in large maps. This column is not shown by default. Not present for absolute binding and solubility FEP, or for protein FEP calculations run with FEP+ residue scanning.

The table also has a shortcut menu, with which you can perform the following actions:

  • Export Structures—Export the structures in the selected rows in Maestro or (3D) SD format. To export in 2D format, use the 2D Viewer Panel.
  • Select All—Select all the table rows.
  • Select Inverse—Invert the selection of table rows. The selected rows are deselected, and the unselected rows are selected.
  • Set as Reference—Use the selected rows as the set of reference ligands.
  • Set as Top of Assay—Mark the selected ligands as ones whose experimental affinity is above the upper limit of the assay, and therefore a reliable error cannot be assigned. These ligands are excluded from cycle closure calculations and from the statistical analysis in the correlation plots. A > sign is inserted before the affinity value to show its relation to the assay limit.
  • Set as Bottom of Assay—Mark the selected ligands as ones whose experimental affinity is below the lower limit of the assay and therefore a reliable error cannot be assigned. These ligands are excluded from cycle closure calculations and from the statistical analysis in the correlation plots. A < sign is inserted before the affinity value to show its relation to the assay limit.
  • Clear Top/Bottom of Assay—Clear the designation of the ligand as outside the assay range.
  • Show Representative Structures—Add an entry group in the Project Table containing the representative structures of the selected ligands for each connection in the map to these ligands, and show them in the Workspace in a tiled view, replacing the Workspace. The group is named Node representatives, and contains a subgroup for the representatives of each selected ligand, if there is more than one ligand selected. The entries in the group are replaced if you show a different set of representative structures.
  • Clear Affinity Data—Clear the experimental affinity and error data from the selected rows.
  • Delete—Delete the ligand from the map. You can also use the Delete key.

Related Topics