[ Make a Hitlist | Reload | Displaying Docking Results | SDF to Hitlist | Scan Hits | View Stack Conformations | Post-Screen Analysis ]

• Docking/Browse/Scan Hits - If you have docked a multi-ligand file (eg SDF) or if you want to go back and see a single docked structure you can scan the structures using this option.
• Docking/Browse/Stack Conformation - View other possible conformations for the docked ligand ranked by energy.
• Docking/Make Hit List - Create a table of docked compounds and their available energies or scores.

The results of the docking are saved in the following files

PROJECTNAME_LIGANDNAME.ob #icm-object file with best solutions for each ligand
PROJECTNAME_*.cnf         #icm conformational stack files with multiple docked conf.

The results of the docking job using ICM-VLS (separate license required) are saved in the following files:

PROJECTNAME_answers*.ob  #icm-object file with best solutions for each ligand
PROJECTNAME_*.cnf        # icm conformational stack files with multiple docked conf.
PROJECTNAME_*.ou         # output file where various messages are stored eg.SCORE

[ Hitlist Column Guide | Hitlist Columns | Analyzing the Hitlist | Hitlist Export ]

To create a Hitlist:

• Select Docking/Make Hit List.
• Enter the docking Project Name.
• Use the browse button to locate the docking results file, typically named PROJECTNAME_answers.ob. Use the wildcard * to combine multiple answer files, for example PROJECTNAME_answers*.ob. Parallel jobs may generate separate answer files; select a pattern that matches the files produced by your run.
• Select 2D/3D to include chemical depictions and 3D coordinates. For a large hitlist, importing scores only can reduce loading time and memory use.
• Select Select Top Hits and enter a value in the corresponding box to create a Hitlist containing only the top N ranked compounds.
• Select Unique if the same compound has been included in multiple docking runs. In this case, only the result with the best docking score will be retained.
• Select Import Original Columns to include columns from the original SDF file used for docking, such as compound ID, catalog number, or other associated properties.
• Click OK to generate the Hitlist.

The resulting Hitlist is displayed as a sortable table containing the docked compounds and their associated docking properties.

A single click on a Hitlist row loads the selected ligand together with the receptor. Once a row is selected, the {up and down cursor keys} can be used to quickly browse through the docked compounds.

A double click opens the conformational stack for that ligand, allowing alternative docked poses to be inspected.

The display toggle can be used to quickly show or hide the currently selected ligand pose.

The columns displayed in the Hitlist depend on the ICM license and the type of docking calculation performed.

Hitlist Columns with ICM-VLS

• IX — Index of the compound in the original docked database.
• Score — The ICM docking score used to rank the compounds. More negative values indicate a more favorable predicted interaction. Scores of approximately -32 or lower are often considered favorable, although the absolute value is receptor-dependent. For example, exposed binding sites or sites containing metal ions may produce different score ranges.
• Natom — Number of atoms in the docked ligand.
• Nflex — Number of flexible or rotatable torsions in the ligand.
• Hbond — Hydrogen-bond interaction energy. Lower values indicate more favorable hydrogen-bonding interactions.
• Hphob — Hydrophobic contribution associated with exposure of non-polar surface to water. Lower values are more favorable.
• VwInt — Explicit van der Waals interaction energy between the ligand and receptor. Lower values indicate more favorable van der Waals interactions.
• Eintl — Internal conformational strain energy of the ligand. This describes the energetic cost of adopting the docked conformation relative to a low-energy unbound conformation. Lower values are preferred.

The unbound reference is determined by generating an ensemble of low-energy ligand conformations using the MMFF94s force field. The energy of the docked conformation is then compared with the lowest-energy reference conformer using the same force field.

As a general guideline, an Eintl cutoff of approximately 5–10 can be useful when filtering docking results. The appropriate cutoff depends on how restrictive the analysis should be. Some flexibility is advisable because strain-energy estimates contain uncertainty, the receptor is not fully relaxed during docking, and larger ligands may naturally accumulate greater conformational strain.

Eintl also contributes to the physics-based ICM Score, with a default weighting factor of 0.6.

• Dsolv — Desolvation penalty associated primarily with exposed hydrogen-bond donors and acceptors. Lower values are preferred.
• SolEl — Change in electrostatic solvation energy upon ligand binding. Lower values are more favorable.
• dTSc — Estimated entropy penalty associated with changes in flexible receptor side chains.
• mfScore — Potential of mean force scoring term.
• RTCNN Score — Neural-network-based score used to evaluate the predicted protein-ligand complex. More negative values indicate a more favorable predicted interaction.
• RecConf — Receptor conformation used for the docking pose. This column is present when docking has been performed against multiple receptor conformations, for example using Docking/Flexible Receptor/Setup 4D Grid**.

Hitlist Columns with ICM-Pro without an ICM-VLS License

For standard ICM-Pro docking, the Hitlist reports the grid-based docking energy and its principal components.

• Edoc — Overall grid docking energy. Lower values are more favorable. Edoc combines the receptor-ligand interaction terms listed below together with the ligand internal energy or conformational strain. The values are reported in kcal/mol and are intended primarily for ranking docked poses.
• Egb — Hydrogen-bond grid energy.
• Ege — Electrostatic grid potential.
• Egs — Hydrophobic grid potential.
• Egv — Grid-based van der Waals interaction energy, combining the attractive and repulsive van der Waals grid terms.

See the Hitlist Column Guide for the available docking energies, scores, and molecular properties.

Sorting the Results

To sort the Hitlist:

• Click the column header (for example, Score) to display the sorting arrows and toggle the sort order.
• Choose the required sorting direction.

For virtual screening results, the table is commonly sorted by Score, with the most negative docking scores at the top.

Browsing Docked Compounds

Single-click a row in the Hitlist to load the selected ligand together with its receptor.

Once a row has been selected, use the up and down cursor keys to move through the Hitlist. The ligand displayed in the 3D window will update as you move from one row to another, providing a convenient way to rapidly inspect the docking results.

Saving a Docked Complex

Once the ligand and receptor are contained in the same object, the complete complex can be saved as a PDB file:

• Right-click on the complex in the ICM Workspace.
• Select Save As.
• Choose PDB (.pdb, .ent) as the file type.
• Enter a filename and save the structure.

Viewing Alternative Docked Poses

Each ligand may have multiple docked conformations stored in its conformational stack.

• Double-click a ligand in the Hitlist to open its stack of alternative docked conformations.
• Single-click a row in the stack table, or use the up and down cursor keys, to browse the alternative poses.
• Double-click a stack entry to load that ligand-receptor complex into the ICM Workspace.

Additional Hitlist Analysis

Additional post-docking analysis and visualization tools are available from the Tools panel on the right side of the Hitlist.

These tools can be used to further inspect, filter, visualize, and prioritize compounds after docking.

How to sort the hitlist. Right click on a column header and select "Sort". For example you may want to sort by docking score.

Single click. A single click on a row in the hitlist will load the ligand and receptor complex in one object.

Save a complex as a PDB file. If the ligand and receptor are in the same object you can save them both as a PDB file. Right click on the name of the complex in the ICM Workspace. Select "Save as" and then a Windows dialog window will be displayed. Use the drop down button to select Type PDB (.pdb .ent).

A docking hitlist can be made into a standalone docking project file to share with others and open in locations away from the docking directory. This can be done by:

• Make the docking hitlist Docking/Make Hitlist.
• Right click on the hitlist header tab (see image below).
• Select Convert To Standalone Hitlist
• File/ Save Project and save the project as an .icb file that others can view using ICM or the free ICM-Browser.

Select Docking/Open Project and open the required docking project. You can then review its results or use its receptor maps for another docking calculation.

In ICM version 3.7-2 and earlier, use Docking/Set Project and enter the case-sensitive project name.

Use the extra panel in the hitlist to control the display of ligand-receptor complexes:

• Single click on one row of your hitlist to load the ligand (usually labeled m) into the receptor object (_rec object). You can then use the up and down cursor keys on your keyboard to browse through the chemical table, or single-click individual rows to display specific ligands.
• Click on the Extra panel button on the hitlist.
• Select the Tools tab.
• Go to the Visualizations section and use the drop down button to choose "Pretty View".
• Click on the Visualizations option and the complex will be displayed in "Pretty View".
• When browsing the hitlist you can also mark chemicals as interesting using Mark Row options.

The same panel can be used to display:

• Pocket Surface a mesh representation of the ligand binding pocket colored by properties of the ligand (opposite of pocket skin below). White=aromatic lipophilic, Green=non-aromatic other (mostly aliphatic) lipophilic surface, Red=hydrogen bonding acceptor potential, Blue=hydrogen bond donor potential.
• Pocket Skin - a surface colored by the binding properties of the pocket. White=aromatic lipophilic, Green=non-aromatic other (mostly aliphatic) lipophilic surface, Red=hydrogen bonding acceptor potential, Blue=hydrogen bond donor potential.
• Atom Energies - contribution of each atom to the Docking Score.
• Clash Volumes - highlights any clashes between ligand and receptor.

Creating a Hitlist from Pre-Docked 3D Ligands

This example describes how to import pre-docked 3D ligands from an SDF file, associate them with an ICM docking project, convert the table into an ICM Hitlist, and use the Hitlist analysis tools to examine protein-ligand interactions.

A video demonstrating this workflow is available here:

How to make a Docking hitlist from a SDF file containing 3D ligands

Step 1: Import and Convert the Receptor PDB File

• Select File/Open and open the receptor PDB file. [00:00:33]
• Convert the PDB structure into an ICM object. [00:00:47]
• Choose whether you want to keep any water molecules present in the structure.
• Select Replace the Original to replace the original PDB object with the converted ICM object.

Step 2: Load the Pre-Docked 3D Ligands

• Select File/Open and open the SD/SDF file containing the pre-docked 3D ligands. [00:01:03]
• To inspect the ligand poses in 3D, right-click on the mol column header and select Set 3D Browse Mode. [00:01:18]
• Check or uncheck individual ligand rows to toggle their 3D display in the graphics window. [00:01:24]

Step 3: Set Up the Docking Project

A docking project is required so that ICM can associate the imported ligand poses with the appropriate receptor and binding site.

• Select one of the docked ligands in the table to define the approximate location of the binding site. [00:01:40]
• Select Docking/New Project. [00:01:51]
• Enter a name for the docking project, for example outsideDock. [00:01:57]
• Select the receptor from the Receptor Object menu, select Define Site Around Selected Ligand, and click OK. [00:02:07]
• Inspect the resulting docking box and probe placement. If necessary, increase the dimensions of the docking box to ensure that it encompasses the imported ligand poses, particularly when working with larger ligands. [00:02:21]

Step 4: Convert the SDF Table into an ICM Hitlist

The imported SDF table can be converted into an ICM docking Hitlist using the following macro.

• Open the ICM Terminal Window. [00:02:38]
• Enter the following command: [00:02:56]

scanConvertTable2Hitlist [mySDFFileName] [Docking_Project_Name]

The macro dialog will open.

• For Table Name, enter the table name containing the imported 3D ligand poses, for example Screen_Hitlist_3D. [00:03:17]
• For Project Name, enter the docking project name , for example outsideDock. [00:03:22]
• Click OK to convert the table into an ICM docking hitlist. [00:03:34]

The resulting Hitlist associates each imported ligand pose with the receptor and docking project, allowing the standard Hitlist visualization and analysis tools to be used.

Step 5: Analyze the Docking Hitlist

Select Windows/Table and open the newly created Hitlist. [00:03:47]

Click the Tools icon on the Hitlist panel to access the available analysis options. [00:03:58]

Interaction Fingerprints and Clustering

Interaction fingerprints provide a compact description of the interactions formed between each ligand pose and the receptor.

• Select the interaction fingerprint property and click Calculate Property to calculate the interaction fingerprints. [00:04:21]
• Select Clustering to group the ligand poses according to the similarity of their protein-ligand interactions. [00:04:30]
• Representative compounds or cluster centers can then be selected and compared using the docking score or other Hitlist properties.

Buried Surface Area and Volume

The Hitlist tools can calculate changes in molecular surface area and volume associated with ligand binding. [00:04:57]

These properties can help identify ligand poses that are well buried within the binding site and provide additional information for comparing alternative poses.

Hydrogen Bond Analysis

Hydrogen-bond properties can be calculated to identify ligands forming interactions with particular receptor atoms or residues. [00:05:06]

• Select the receptor atom or atoms of interest.
• Calculate the appropriate hydrogen-bond property from the Hitlist tools panel.
• The resulting column can be used to identify and rank ligands forming the desired interaction.

APF Pose Similarity

Atomic Property Field (APF) similarity can be used to compare ligand poses with a reference ligand or pocket template. [00:05:25]

This provides an additional method for identifying compounds that reproduce the spatial and physicochemical features of a known or desired binding mode.

Hydrogen-Bond Donors and Acceptors

Properties describing hydrogen-bond donors and acceptors can also be calculated for the ligand and receptor. [00:05:33]

These values can be used together with the other Hitlist properties to help characterize and prioritize the imported docking poses.

Use Docking/Browse/Scan Hits to browse saved docking solutions. For table-based review and ranking, see Make a Docking Hitlist.

Use Docking/Browse/Stack Conformation to inspect stored conformations, or open a ligand's stack from the hitlist. Alternative poses are available only if they were saved during docking.

[ Sort Hitlist | Plot | Complex & H-bond Display | Calculate Properties | APF Cluster | Interaction Fingerprints | Interaction Lists | Visualization ]

Use the hitlist Tools panel to compare molecular properties, inspect receptor contacts, and cluster poses. Combine these analyses with visual inspection and the scoring guidance; a favorable score alone does not establish binding.

For subsequent trajectory analysis, see MD of a Virtual Ligand Screening Hitlist.

Compounds can be sorted according to their SCORE and other properties in the hitlist. To sort the table single click on the column header - see the tables section of this manual for more information about manipulating tables.

The hitlist generated from docking or screening typically contains many columns with numerical data, such as Score, RTCNN score, MolWt, LogP, Number of H-bond donors/acceptors, and others. Visualizing relationships between these columns can be a powerful way to explore trends and prioritize compounds. For example you may want to plot Score (Physics-Based Score) vs RTCNN Score and select those with low values for each. See the data plotting section of the manual here.

When you make the hitlist you will see a panel next to the chemical table called Tools. The options here can be used to:

• Check the option display Hbonds if you would like to display hydrogen bonds when you browse the hitlist.
• Check the option make complex structure if you would like the ligand-receptor complex to be displayed when you browse the hitlist.

The hitlist tools allow you to calculate a range of property expressions that provide deeper insight into how all the ligands in your hitlist interact with the receptor. By pressing the 'gear' button in the top-right corner of the hitlist table, you can open the Tools panel and access these calculations through the Property Expression menu.

Options include measuring ligand charge, buried surface area, conformational volume change, hydrogen bond interactions, pharmacophore RMSD, cis/trans amide angle, and spatial relationships to receptor selections. Additional functions include pose similarity, interaction fingerprint clustering, and automatic listing of residue-level interactions. These properties help compare docked geometry and interactions when selecting compounds for experimental testing.

The options include:

• Calculate charge of the ligands in the hitlist.

  Computes the net molecular charge of each ligand. Charge influences solubility, membrane permeability, and electrostatic interactions with the binding site.

• Calculate Buried Surface Area (BSA) of the ligands in the hitlist.

  Measures how much ligand surface becomes inaccessible to solvent upon binding. Use this descriptor to compare burial alongside pose quality and other scores.

• Calculate volume change of the ligands in the hitlist.

  Reports the volume-change property for the selected ligand-receptor geometry. Interpret it alongside the other geometric descriptors; it is not a direct measure of strain or binding affinity.

• Calculate whether the ligand makes a hydrogen bond with a selection.

  Select a receptor residue or atom first. The scoring function ranges from -2 to 0; more negative values indicate stronger hydrogen bonds. The score uses donor-acceptor distance and angle to approximate typical hydrogen bond energetics. A value near 0 means no significant interaction; values approaching -2 reflect optimal geometry.

• Calculate pharmacophore RMSD.

  Measures the root-mean-square deviation between a ligand’s pharmacophoric features and a reference model. Requires an object named pharma with the pharmacophore loaded in the workspace. Useful for assessing alignment to a pharmacophore hypothesis.

• Calculate cis/trans amide angle of the ligands in the hitlist.

  Checks amide bond geometry. Most amides are trans; cis can be less stable or less favorable for binding. Helps flag unusual or strained conformations.

• Calculate distance to selection.

  Select a receptor atom or residue first. Computes the distance between the selection and each ligand, useful for measuring proximity to key residues or functional groups.

• Calculate non-overlap with selection.

  Select a receptor residue first. Evaluates how much of the ligand avoids steric overlap with the selection to help detect potential clashes.

• APF pose similarity to a selected ligand.

  Uses Atomic Property Fields (APF) to compare ligand poses against a chosen reference ligand, incorporating shape and pharmacophoric properties to identify pose mimicry.

• Calculate and cluster the interaction fingerprints.

  Encodes ligand-receptor interactions into a binary fingerprint (e.g., hydrogen bond donor/acceptor, apolar). The resulting column can be clustered to group ligands with similar interaction patterns.

• Calculate a list of the interactions.

  Generates columns per pocket residue with 1/0 values indicating whether the ligand forms donor, acceptor, or apolar interactions. Produces a residue-level interaction map for the hitlist.

Each of these properties will be placed in the hitlist table as a new column. You can choose a column name before calculating using the Column name dialog box. Click on the Calculate property button to run the calculation.

• Make the hitlist (Docking/Make Hitlist)
• Press the Cluster by APF button on the Tools panel (right hand side of hitlist table).
• A tree will be displayed clustering the pose similarity of the compounds by APF fit.
• The distance matrix is added to the hitlist.

Interaction fingerprints encode receptor contacts, including hydrogen bonds, as bit strings. Use them to select compounds with shared contacts or to retain a diverse set of interaction patterns. Alternatively, cluster poses by APF similarity.

Step 1: Calculate Interaction Fingerprints Setup and run the docking and then make a hitlist. Optional: Make an orange selection of the ligand binding pocket. If no selection is made ICM will use the binding pocket as defined in the docking project. Open the extra panel in the hitlist table. Choose the option Interaction FPs in the Descriptor Calculator section of the panel. Enter a name for the column. Click calculate property.

Step 2: Once the calculation has finished a column will be added to the hitlist table.

Step 3: Cluster the Fingerprints Select the fingerprint column. Click on the cluster button. Choose the options shown in the dialog window above.

Step 4: Select representative centers or conserved binding interactions. Drag the distance bar to change the tree. Click on the branches of the tree to select (use CTRL for non-contiguous selections). Right click in "white space" and choose representative centers.

In these lists, residues are labeled (1 or 0) according to their interaction type or property, helping you interpret their role in ligand binding:

• apo - Apolar. The residue interacts with the ligand through hydrophobic (non-polar) contacts, such as van der Waals interactions. These are important for stabilizing ligand binding through shape complementarity and desolvation.
• hba - Hydrogen bond acceptor. This residue accepts a hydrogen bond from a donor group on the ligand.
• hbd - Hydrogen bond donor. This residue donates a hydrogen bond to an acceptor group on the ligand.

Once you have made a hitlist of the screening results you can use the panel on the right hand side of the hitlist to change visualization options. The available options are:

• pocketSurface = The surface of the ligand binding pocket. White=aromatic lipophilic, Green=non-aromatic other (mostly aliphatic) lipophilic surface, Red=hydrogen bonding acceptor potential, Blue=hydrogen bond donor potential
• pocketSkin = A skin representation of the neighboring residues.
• Pretty = A default representation for ligand and receptor (see image below).
• atomEnergies = An energy value for each atom in the ligand is displayed.Green and low numbers indicate a favorable contribution to the score.
• clashVolumes = Highlights any clashes between ligand and receptor.