Conformational Analysis for Small Molecules Using MacroModel and ConfGen

Tutorial Created with Software Release: 2025-3
Topics: Hit Discovery, Hit-to-Lead & Lead Optimization, Small Molecule Drug Discovery
Products Used: ConfGen, MacroModel

Tutorial files

21.9 MB
This tutorial is written for use with a 3-button mouse with a scroll wheel.
Words found in the Glossary of Terms are shown like this: Workspacethe 3D display area in the center of the main window, where molecular structures are displayed

 

Tip: You can hover over a glossary term to display its definition. You can click on an image to expand it in the page.
Abstract:

 

In this tutorial, you will investigate tools that are useful for exploring conformational space for small molecules. MacroModel will be used to set up and analyze simple torsions of a single compound to gain a better understanding of the energetic barriers of a small molecule. ConfGen will then be used to screen molecules with diverse linker atoms as it is a fast method geared towards retrieving low energy bioactive conformations.

 

Tutorial Content

  1. Creating Projects and Importing Structures

  1. MacroModel and ConfGen Prerequisites

  1. Scanning Torsions using MacroModel

  1. Screening for Active Conformations using ConfGen

  1. Conclusion and References

  1. Glossary of Terms

1. Creating Projects and Importing Structures

At the start of the session, change the file path to your chosen Working Directorythe location that files are saved in Maestro to make file navigation easier. Each session in Maestro begins with a default Scratch Projecta temporary project in which work is not saved, closing a scratch project removes all current work and begins a new scratch project, which is not saved. A Maestro project stores all your data and has a .prj extension. A project may contain numerous entries corresponding to imported structures, as well as the output of modeling-related tasks. Once a project is created, the project is automatically saved each time a change is made.

Structures can be imported from the PDB directly, or from your Working Directorythe location that files are saved using File > Import Structures, and are added to the Entriesa simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion and Project Tabledisplays the contents of a project and is also an interface for performing operations on selected entries, viewing properties, and organizing structures and data. The Entriesa simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion is located to the left of the Workspacethe 3D display area in the center of the main window, where molecular structures are displayed. The Project Tabledisplays the contents of a project and is also an interface for performing operations on selected entries, viewing properties, and organizing structures and data can be accessed by Ctrl+T (Cmd+T) or Window > Project Table if you would like to see an expanded view of your project data.

  1. Double click the Maestro icon to start Maestro.

Figure 2-1. Change Working Directory option.

  1. Go to File > Change Working Directory.
  2. Find your directory, and click Choose.
  3. Pre-generated input and results files are included for running jobs or examining output. Download the zip file here: https://www.schrodinger.com/sites/default/files/s3/release/current/Tutorials/zip/macromodel_confgen.zip
  4. After downloading the zip file, unzip the contents in your Working Directorythe location that files are saved for ease of access throughout the tutorial.

Figure 2-2. The Open Project panel.

  1. Go to File > Open Project.
  2. Select the file MM_ConfGen.prjzip.
  3. Click Open.
    • Structures are shown in the Entriesa simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion.
    • A structure is includedthe entry is represented in the Workspace, the circle in the In column is blue in the Workspacethe 3D display area in the center of the main window, where molecular structures are displayed.
  4. In the Save scratch project dialog box, click OK.

 

Note: Please see the Glossary of Terms for the distinction between includedthe entry is represented in the Workspace, the circle in the In column is blue and selected(1) the atoms are chosen in the Workspace. These atoms are referred to as "the selection" or "the atom selection". Workspace operations are performed on the selected atoms. (2) The entry is chosen in the Entries (and Project Table) and the row for the entry is highlighted. Project operations are performed on all selected entries .

Figure 2-3. Saving the project in the Save Project panel.

  1. Go to File > Save Project As.
  2. Change the File name to MM_Confgen_tutorial.
  3. Click Save.
    • The project is named MM_Confgen_tutorial.prj.  

 

2. Preparing to Explore Conformational Space

Structure files obtained from the PDB, vendors, and other sources often lack necessary information for performing modeling-related tasks. Typically, these files are missing hydrogens, partial charges, side chains, or whole loop regions. In order to make these structures suitable for modeling tasks, we use the Protein Preparation Workflow to resolve these issues. Similarly, ligand files can be sourced from numerous places, such as vendors or databases, often in the form of 1D or 2D structures with unstandardized chemistry. LigPrep can convert ligand files to 3D structures, with the chemistry properly standardized and extrapolated, ready for use in virtual screening.

In this tutorial, the proteins and ligands have already been prepared in order to save time. However, these preparation steps are a necessary part of conformational analysis and must be done before using MacroModel or ConfGen. Please see the Introduction to Structure Preparation and Visualization tutorial for instructions on using the Protein Preparation Workflow and LigPrep.

Conformer generation is useful in many aspects of both molecular modeling in general and drug discovery in particular. Moreover, the ability to generate a bioactive conformer is a vital prerequisite to any successful computer-aided drug design project. Efficient conformer sets have wide-ranging ramifications in downstream applications. For example, with fewer irrelevant conformations to process, virtual database screens and shape-based similarity searches run to completion in a fraction of the time without sacrificing accuracy.

There are three tools for exploring the conformational space of a ligand within the Schrodinger Small Molecule Drug Discovery suite known as MacroModel, ConfGen, and Prime. Macromodel provides a wealth of conformational search options including those for small molecules, proteins, and protein-ligand complexes. ConfGen is embedded into a number of applications as it is suited to explore large scale conformer generations and is tailored to predict active conformations with successful ligand binding to a receptor. The third tool available is Prime, a protein centric tool used for large structures such as macrocycles. This tutorial will address MacroModel and ConfGen tools to explore the conformational space of small molecules. It is important to choose the most appropriate application for your research project. See the MacroModel Product Overview, ConfGen Product Overview,and Prime Product Overview for more information. For information about generating conformations for Glide Docking, see this KB Article .

3. Scanning Torsions Using MacroModel

In this section, we will use the MacroModel Coordinate Scan to set up and analyze simple torsions of a single compound to gain a better understanding of the energetic barriers of a small molecule. We will superimpose the output conformations to a common core, for easier visualization. Next, we will use the potential energy surface to find low energy conformations of a small molecule. These steps are a prelude to a full conformational search, which can explore many torsions of a small molecule simultaneously or systematically. We will use the potential energy surface to find low energy conformations of a small molecule. Investigating conformational space is important for understanding structural-property dependence, and for constructing initial models for Molecular Dynamics simulations.

3.1 Set up a torsional scan

Figure 3-1. Including and selecting the Ddrive entry.

  1. Confirm the Ddrive entry is includedthe entry is represented in the Workspace, the circle in the In column is blue and selected(1) the atoms are chosen in the Workspace. These atoms are referred to as "the selection" or "the atom selection". Workspace operations are performed on the selected atoms. (2) The entry is chosen in the Entries (and Project Table) and the row for the entry is highlighted. Project operations are performed on all selected entries in the Entriesa simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion.
    • The structure is shown in the Workspacethe 3D display area in the center of the main window, where molecular structures are displayed.

Note: Atom number labels were added from the Style toolbox by clicking the  Apply Labels arrow and choosing Element + Atom Number.

Figure 3-2. The Coordinate Scan option in MacroModel.

  1. Go to Tasks > Browse > MacroModel > Coordinate Scan.
    • The Coordinate Scan panel opens.

Figure 3-3. The Scan tab of the Coordinate Scan panel.

  1. For Use structures from, choose Workspace (included entry).
  2. Go to the Scan tab.
  3. For Coordinate Type, choose Dihedral.
    • A banner appears prompting you to pick four atoms to add dihedral coordinate.

Figure 3-4. Selecting atoms to define Torsion 1.

  1. In the Workspacethe 3D display area in the center of the main window, where molecular structures are displayed, select(1) the atoms are chosen in the Workspace. These atoms are referred to as "the selection" or "the atom selection". Workspace operations are performed on the selected atoms. (2) The entry is chosen in the Entries (and Project Table) and the row for the entry is highlighted. Project operations are performed on all selected entries atom numbers 1, 14, 15, and 16.
    • Atoms are highlighted in cubes.
    • Torsion 1 is defined.

Figure 3-5. Selecting atoms to define Torsion 2.

  1. Select(1) the atoms are chosen in the Workspace. These atoms are referred to as "the selection" or "the atom selection". Workspace operations are performed on the selected atoms. (2) The entry is chosen in the Entries (and Project Table) and the row for the entry is highlighted. Project operations are performed on all selected entries atom numbers 1, 6, 25, and 26.
    • Atoms are highlighted in cubes.
    • Torsion 2 is defined.

Figure 3-6. The Potential tab of the coordinate Scan panel.

  1. In the Coordinate Scan panel, go to the Potential tab.
  2. For Solvent, choose None.
    • A gas phase minimization will be run.
  3. For Job name, type mmod_Ddrive.
  4. Click Run.
    • This job takes ~30 seconds.
    • A banner appears and a new group mmod_Ddrive-out is added to the Entriesa simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion once the job is completed.

Optional: Run this job in water and then chloroform solvents to compare intramolecular interactions in the conformations.

Note: MacroModel also has substantial options for controlling force fields, constraints, and settings associated with navigating a potential energy surface.

  1. Close the Coordinate Scan panel.

3.2 Analyze torsional scan results

Figure 3-7. Display properties in the Entry List.

  1. In the top right corner of Entriesa simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion, click the Change table settings (three vertical dots) and choose Show Property.
    • The Show Properties in Table dialog box opens.

Figure 3-8. Adding properties to the Entries table.

  1. In the dialog box, click Choose.
  2. Search and select Potential Energy-OPLS3 and Relative Energy-OPLS3 from the list.
  3. Click OK.
    • The Potential Energy and Relative Energy properties are added to the Entriesa simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion table.
    • Both properties are given in kJ/mol.
    • You may need to click and drag the edge of the Entriesa simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion table to see the added properties.

Note: OPLS4 calculations will still use this OPLS3 property category for the time being while we update the remainder of the panel. Notice that once imported, the Entriesa simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion property headings are more general.

The relative energies of small molecule conformations play a crucial role in determining the shape, function, and activity of a ligand.

Figure 3-9. The minimum energy structure.

Note: The last entry in the mmod_Ddrive-out

group is the lowest energy structure found from scanning the two dihedrals. The lowest energy structure gives us an indication of how adaptable the molecule is and how much strain is needed for it to adopt a particular conformation.

Figure 3-10. Renaming the Ddrive entry and moving it to the mmod_Ddrive-out group.

  1. Double-click the Ddrive entry title and rename it to Ddrive_Starting_Structure.
  2. Right-click the renamed entry and choose Move to > Other row.
    • The Move to Row dialog box opens.
  3. For the Row number, type 10.
  4. Click Move.
    • The Ddrive_Staring_Structure is moved to the mmod_Ddrive-out group as its top entry.
    • It is included and selected.

Figure 3-11. The Superposition option in the Structure Alignment.

  1. Select the mmod_Ddrive-out group by clicking on the group heading.
  2. Go to Tasks > Browse > Structure Alignment > Superposition.
    • The Superposition panel opens.

Figure 3-12. The Superposition panel.

  1. For Superimpose entries from, choose Project Table (selected).
  2. For Reference structure, choose             9: Ddrive_Starting_Structure.
  3. Check the box for Add property to Project Table option.
  4. For Choose method, choose Substructures.
  5. For Define structures for superposition using, choose SMARTS.
  6. Return to the Workspacethe 3D display area in the center of the main window, where molecular structures are displayed.

Figure 3-13. Selecting the atoms in the pyrimidine core.

  1. Type A on the keyboard.
    • Atom selection mode is activated.
  2. In the Workspacethe 3D display area in the center of the main window, where molecular structures are displayed, use shift-click to select(1) the atoms are chosen in the Workspace. These atoms are referred to as "the selection" or "the atom selection". Workspace operations are performed on the selected atoms. (2) The entry is chosen in the Entries (and Project Table) and the row for the entry is highlighted. Project operations are performed on all selected entries all atoms in the pyrimidine core.
  3. In the Superposition panel, click Get from Selection.
  4. Click Superimpose Structures.
    • The selected structures are aligned to the pyrimidine core.
    • RSMDs for the structures are shown in the Results table at the bottom of the panel.
  5. Close the Superposition panel.

Figure 3-14. Fixing the Ddrive_Starting_Structure in the Workspace and steeping through the conformations.

  1. In the Entriesa simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion, double-click the In circle next to Ddrive_Starting_Structure.
    • The structure is fixed in the Workspacethe 3D display area in the center of the main window, where molecular structures are displayed.
  2. Includethe entry is represented in the Workspace, the circle in the In column is blue the second entry.
  3. Use the left and right arrow keys to step through the conformations.

Figure 3-15. Including multiple entries in the Workspace.

Note: Use shift-click to include contiguous entries or ctrl-click (cmd-click) to include non-contiguous entries in the Workspacethe 3D display area in the center of the main window, where molecular structures are displayed. The 300 lowest energy conformations are shown in the adjacent figure.

3.3 View the potential energy surface

A coordinate scan produces a contour diagram describing the molecular mechanics potential energy of a structure, relative to the value of either one or two coordinates (distances, angles, or dihedrals), can be generated with MacroModel. These exercises demonstrate how to produce a contour diagram describing the variation in energy of a molecule with respect to rotation of two dihedral angles.

Figure 3-16. The Plot Coordinate Scan option in the MacroModel application.

  1. Go to Tasks > Browse > MacroModel > Plot Coordinate Scan.
    • The Plot Coordinate Scan Results panel opens.

Note: The potential energy surface of a compound can help with understanding key aspects of a molecule's behavior.

Figure 3-17. Opening the coordinate scan output.

  1. At the top of the panel, click Load Results.
    • Select a grid file dialog box opens.
  2. Double-click mmod_Ddrive folder and choose mmod_Ddrive-out.grd.
  3. Click Open.
    • The potential energy landscape is shown, colored rainbow.
    • Low energies are shown in blue, high energies are shown in red.

Figure 3-18. The Plot Coordinate Scan Results panel.

  1. Set the Energy scale to Absolute.

Note: The energy scale is absolute because we are only studying a single molecule, rather than comparing several molecules.

Note: This plot shows there are large patches of lower energy with relatively sparse contour spacing between them. This suggests a reasonable freedom of movement of the two torsions relative to each other.

  1. Close the Plot Coordinate Scan Results panel.

Figure 3-19. Applying CPK representation to the starting and lowest energy structures.

  1. Scroll to the bottom of the mmod_Ddrive-out group and includethe entry is represented in the Workspace, the circle in the In column is blue the Minimum E. structure during drive entry.
    • The Ddrive_Starting_Structure should still be fixed in the Workspacethe 3D display area in the center of the main window, where molecular structures are displayed.
  2. Go to the Style Toolbox and choose Apply CPK representation.

 

Figure 3-20. Tiled view of a low and high energy conformation, showing a CH2 steric clash in yellow.

  1. Tile the Workspacethe 3D display area in the center of the main window, where molecular structures are displayed by using the Workspace Layout Toggles (bottom right corner).
    • The Workspacethe 3D display area in the center of the main window, where molecular structures are displayed is tiled.
    • The steric clash between the CH2 group and phenyl ring can be visualized.

Note: Looking into the energetic components of the system can help explain a potential energy surface.

  1. Un-tile the Workspacethe 3D display area in the center of the main window, where molecular structures are displayed by deselecting Tile by.
  2. Go to Workspace and choose Clear Workspace.

Figure 3-21. Toggle properties on and off with the Property Tree.

  1. Type ctrl-T (cmd-T).
    • The Project Table displays the contents of a project and is also an interface for performing operations on selected entries, viewing properties, and organizing structures and dataopens.
  2. Click Tree to open the Property Tree.
    • Different calculated properties can be toggled on and off.
    • Click the arrow next to each application to view more properties.
  3. Double-click All.
    • All the properties are now hidden.
  4. Open the tree to  MacroModel > Secondary.
  5. Under Secondary, check Bend Energy-S-OPLS, RMS Derivative-S-OPLS and Van der Waal Energy- S-OPLS.
    • The Project Tabledisplays the contents of a project and is also an interface for performing operations on selected entries, viewing properties, and organizing structures and data is updated with the chosen properties.

There is a high VdW energy between the phenyl group and the nearby CH2 group of Torsion 1. This causes the pyrimidine core to distort and result in a high energy bend.

4. Screening for Active Conformations using ConfGen

As part of a medicinal chemistry exploration project, it is often helpful to change a single-atom linker in a molecule to evaluate the impact it has. We will change the linker atom in a series of molecules and visualize the variation of active conformations. These torsion differences often have implications for the shape of the ligand. We will be using ConfGen instead of MacroModel due to its speed and ability to generate bioactive conformations. You may choose to also perform the steps in this section using MacroModel to compare your results to Section 3 and to the ConfGen conformations generated here in Section 4. While it's impossible for a conformer search algorithm to determine a flexible ligand's bioactive conformer with absolute confidence, carefully considered search criteria do allow an algorithm to reject conformers likely to be high energy or inactive. Beyond merely expediting the conformer search process, this approach creates efficiently sized conformer sets that nevertheless contain a reasonable approximation of the bioactive geometry.

4.1 Set up the screening

Figure 4-1. Selecting and including all the entries of the Phenyl-linker-Pyridyl group.

  1. In the Entriesa simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion, expand and select(1) the atoms are chosen in the Workspace. These atoms are referred to as "the selection" or "the atom selection". Workspace operations are performed on the selected atoms. (2) The entry is chosen in the Entries (and Project Table) and the row for the entry is highlighted. Project operations are performed on all selected entries the Phenyl-linker-Pyridyl group by clicking on the group heading.
  2. Right-click the selection and choose Include.
    • All the entries in the group are included in the Workspacethe 3D display area in the center of the main window, where molecular structures are displayed.

Figure 4-2. The Bioactive Search option in the Structure Analysis.

  1. Go to Tasks > Browse > Structure Analysis > Bioactive Search.
    • The ConfGen panel opens.

Figure 4-3. The ConfGen panel.

  1. For Use structures from, choose Workspace (4 entries).
  2. Click Load.
  3. Set the Target number of conformations to 50.
  4. Change the Job name to Phenyl-linker-Pyridyl_ConfGen
  5. Click Run.
    • This job takes ~30 seconds.
    • A banner appears and a new group Phenyl-linker-Pyridyl_ConfGen-in-out is added to the Entriesa simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion.
  6. Close the confGen panel.

Figure 4-4. Comparing the Ph-S-Py and Ddrive_Starting_Structure in the Workspace.

  1. In the Entriesa simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion, Ctrl+Click (Cmd+Click) to includethe entry is represented in the Workspace, the circle in the In column is blue a generated conformation of Ph-S-Py group and Ddrive_Starting_Structure.
    • C-S has a greater bond length than the original C-S bond and the original Ph-S-Py compound.

Optional: Select Measure to measure and compare bond lengths in the structures.

4.2 Analyze the results of the linker series

Figure 4-5. Adding ConfGen energy properties to the Entries table.

  1. At the top right corner of the Entriesa simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion table, click Change table settings (three vertical dots) and choose Show Property.
    • The Show Properties in Table dialog box opens.
  2. In the dialog box, click Choose.
  3. Search and select energy and relative energy properties from the list.
  4. Click OK.
    • The Energy and Relative Energy properties are added to the Entriesa simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion table.
    • Both properties are given in kJ/mol.
    • You may need to click and drag the edge of the Entriesa simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion table to see the added properties.

Figure 4-6. Sorting the energy in ascending order.

  1. Right-click energy and choose Sort Selected (Ascending).

Figure 4-7. Group the ConfGen result groups.

  1. Go to Workspace and choose Clear Workspace.
  2. Select(1) the atoms are chosen in the Workspace. These atoms are referred to as "the selection" or "the atom selection". Workspace operations are performed on the selected atoms. (2) The entry is chosen in the Entries (and Project Table) and the row for the entry is highlighted. Project operations are performed on all selected entries the Phenyl-linker-Pyridyl_ConfGen group by clicking on the group heading.
  3. Right-click the selection and choose Include.
  4. Click Continue to the warning box that appears.
    • The entire group is included in the Workspacethe 3D display area in the center of the main window, where molecular structures are displayed.

Figure 4-8. Tiling the group entries.

  1. Click the Workspace Configuration Toggle (bottom right corner) and tile your Workspacethe 3D display area in the center of the main window, where molecular structures are displayed by group.
    • Four groups with overlaid structures are present in the Workspacethe 3D display area in the center of the main window, where molecular structures are displayed.

Figure 4-9. Showing all ConfGen results by group in Tile view.

  1. Rotate the molecules in the Workspacethe 3D display area in the center of the main window, where molecular structures are displayed
  2. Right-click and select Clear Workspace

Note: These structures are not aligned, but already you can see differences in the conformation due to changes in the linker atoms.

Optional: Align each group in turn to a common phenyl core to more easily see changes in one conformation to the next.

Figure 4-10. Tile view of only the four energy minimized conformations.

  1. Using cmd/ctrl-click, includethe entry is represented in the Workspace, the circle in the In column is blue the lowest energy conformer in Ph-NH2-Py, Ph-CH2-Py, and Ph-S-Py groups using the energy property.
  2. Double click the Presets button to apply Maestro presets to these compounds
    • Notice differences in these active conformations.
  3. Un-tile the Workspacethe 3D display area in the center of the main window, where molecular structures are displayed by expanding the Workspace Configuration (plus icon in the bottom right corner) toggle and deselecting Tile by.

Figure 4-11. Superimpose included entries by SMARTS.

  1. With the lowest energy conformations still included in the Workspacethe 3D display area in the center of the main window, where molecular structures are displayed, go to Tasks > Browse > Structure Alignment > Superimposition.
    • The Superposition panel opens.
  2. For Superimpose entries from, choose Workspace.
  3. For Reference Structure, choose Ph-NH2-Py.
  4. For Choose method, select Substructures.
  5. For Define structures for superposition using, choose SMARTS.
  6. In the Workspacethe 3D display area in the center of the main window, where molecular structures are displayed, use shift-click to select(1) the atoms are chosen in the Workspace. These atoms are referred to as "the selection" or "the atom selection". Workspace operations are performed on the selected atoms. (2) The entry is chosen in the Entries (and Project Table) and the row for the entry is highlighted. Project operations are performed on all selected entries all pyridine carbon atoms.
  7. In the Superposition panel, click Get from Selection.
  8. Choose Superimpose Structure.

Figure 4-12. The lowest energy active conformations of the linker series compounds superimposed.

Note: Changing the linker from an oxygen (in the structure with grey carbons) to a sulfur (in the structure with green carbons), alters the phenyl ring orientation with respect to the pyridyl nitrogen. The CH2 linker induces the least planar conformation, due to sterics, while the NH2 linker is most coplanar with the pyridyl ring.

Note: This was done via ConfGen so that only active conformations were chosen. Different results will be returned if the same comparison is done using MacroModel.

 

Figure 4-13. The Phenyl-O-Group in the Entries.

Optional: A Phenyl-O-Group has also been included in the Entriesa simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion. If you would like more practice with MacroModel or ConfGen please use these structures to investigate the CH3,CFH2,CF2H, and CF3 groups and how they affect torsion parameters and active conformations of these ligands.

5.    Conclusions and References

MacroModel is a powerful tool to explore the full range of conformations for small molecules, and can also be used to analyze protein-ligand complexes. You learned how specific settings can make a difference to the conformational output, so understanding the choices you make are important to the results. Through the exploration of small molecule active conformations using ConfGen, you observed how conformations can vary due to a single atom change and how this information can be used in lead optimization.

For further learning:

 

6. Glossary of Terms

Entries - a simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion

included - the entry is represented in the Workspace, the circle in the In column is blue

incorporated - once a job is finished, output files from the Working directory are added to the project and shown in the Entry List and Project Table

Project Table - displays the contents of a project and is also an interface for performing operations on selected entries, viewing properties, and organizing structures and data

Scratch Project - a temporary project in which work is not saved, closing a scratch project removes all current work and begins a new scratch project

selected - (1) the atoms are chosen in the Workspace. These atoms are referred to as "the selection" or "the atom selection". Workspace operations are performed on the selected atoms. (2) The entry is chosen in the Entries (and Project Table) and the row for the entry is highlighted. Project operations are performed on all selected entries

Working Directory - the location that files are saved

Workspace - the 3D display area in the center of the main window, where molecular structures are displayed