Crystal Structure Prediction: Part 2

Tutorial Created with Software Release: 2026-3
Topics: Pharmaceutical Formulations
Products Used: Crystal Structure Prediction, MS Maestro

Tutorial files

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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

 

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Abstract:

In this tutorial, we will learn how to run the crystal structure prediction workflows for salts.

Tutorial Content

  1. Introduction to Crystal Structure Prediction: Part 2

  1. Creating Projects and Importing Structures

  1. Running the Crystal Structure Prediction Workflow for Salts

  1. Analyzing the Crystal Structure Prediction Workflow for Salts

  1. Conclusion and References

  1. Glossary of Terms

1. Introduction to Crystal Structure Prediction: Part 2

The Crystal Structure Prediction (CSP) method in the Schrödinger Suite utilizes a specialized search algorithm and machine learning to predict and rank the energetic stability of a material's polymorphs. This approach is vital in industries like pharmaceuticals to identify potential crystal structures that traditional, costly experiments might miss.

In the Crystal Structure Prediction tutorial, CSP workflows for acetaminophen (Z′=1 and Z′=2) and nitrofurantoin (Z′=1 and monohydrate) are explored. In this tutorial, we will perform a CSP workflow for a sertraline salt. The sertraline salt will first be sketched using the 2D Sketcher. Then the CSP workflow will be performed using the Crystal Structure Prediction and the Crystal Structure Prediction Viewer panels.

2. Creating Projects and Importing Structures

At the start of the session, change the file path to your chosen Working Directorythe location where files are saved in MS Maestro to make file navigation easier. Each session in MS 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 MS 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 saved, the project is automatically saved each time a change is made.

Structures can be built in MS Maestro or can be imported using File > Import Structures (or drag-and-dropped), and are added to the Entry Lista 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 Entry Lista 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 Materials Science icon

Figure 2-1. Change Working Directory option.

  1. Go to File > Change Working Directory
  2. Find your directory, and click Choose
  3. Pre-generated files are included for running jobs or examining output. Download the zip file here: schrodinger.com/sites/default/files/s3/release/current/Tutorials/zip/csp_part2.zip
  4. After downloading the zip file, unzip the contents in your Working Directorythe location where files are saved for ease of access throughout the tutorial

Figure 2-2. Save Project panel.

  1. Go to File > Save Project As
  2. Change the File name to csp_part2_tutorial, click Save
    • The project is now named csp_part2_tutorial.prj

Figure 2-3. Drawing a sertraline salt.

We will proceed to draw the systems that we will use in the subsequent sections using the 2D Sketcher.

  1. Go to Edit > 2D Sketcher
  2. Draw the sertraline salt
    • Sertraline salt is shown in the figure
  3. Click Save as New
  4. Name the entry sertraline_salt
  5. Click OK

3. Running the Crystal Structure Prediction Workflow

In this section, a CSP workflow will be performed on the sertraline salt using the Crystal Structure Prediction panel.

Figure 3-1. Opening the Crystal Structure Prediction panel.

  1. With the sertraline salt entry 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 Entry List (and Project Table) and the row for the entry is highlighted. Project operations are performed on all selected entries and includedthe entry is represented in the Workspace, the circle in the In column is blue, go to Tasks > Materials > Polymorph Prediction > Crystal Structure Prediction

Figure 3-2. Running the Crystal Structure Prediction panel to generate conformers.

  1. Change the Task to Generate conformers
    • Running a conformers job first is best practices to ensure the conformers are what you’d expect before moving to the much longer packing and ranking calculation
  2. Change the Output to Salt crystals with monoatomic ion
  3. Click Load to load the molecule
    • The sertraline salt will now be loaded into the panel
  4. Change the Job name to csp_sertraline_salt_conformers
  5. Adjust the job settings () as needed
    • This job requires a CPU host and should complete in a couple of minutes on 8 CPUs
    • Job Server is required for submission of Crystal Structure Prediction calculations
  6. Click Run or import the CAVVUQ_output_confgen.maegz file from the provided tutorial files
    • The count of generated conformers may not match the number found in the supplied file
  7. Close the Crystal Structure Prediction panel

Figure 3-3. Running the Crystal Structure Prediction panel on the conformers.

  1. When the job is finished, a new entry titled output_confgen is automatically  included in the entry list
  2. With the output_confgen group 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 Entry List (and Project Table) and the row for the entry is highlighted. Project operations are performed on all selected entries, use the Workflow Action Menu (WAM) button () or go to Tasks > Materials > Polymorph Prediction > Crystal Structure Prediction
  3. Change the Task to Perform packing search & ranking
  4. Change the Output to Salt crystals with monoatomic ion
  5. Click Load to load the conformers
    • 52 conformers will now be loaded into the panel
  6. Set Crystalllize with to Cl-
  7. Change the Job name to csp_sertraline_salt
  8. Adjust the job settings () as needed
    • This job requires a CPU and GPU host. This calculation runs thousands of subjobs. Specifying 10,000 CPUs is ideal but will use many resources at once. A balance needs to be achieved between wall time and the use of resources.
    • Job Server is required for submission of Crystal Structure Prediction calculations.
  9. If you would like to run the job, click Run, otherwise, we will proceed with pre-generated results in the next section
  10. Close the Crystal Structure Prediction panel

The calculation will pack the conformers into unit cells by using various space groups and then relaxing the structures and filtering out the highest-energy structures. The relaxation part does a series of relaxations, each of which is followed by a filter. The first uses molecular mechanics (MM) (cheapest), then machine learning force field (MLFF) (medium), then density functional theory (DFT) (most expensive).Checking the "include DFT ranking" box will return the DFT ranking results. Fewer crystals require a DFT run compared to those needing MM.

4. Analyzing the Crystal Structure Prediction Workflow

In this section, CSP workflow results will be viewed using the Crystal Structure Prediction Viewer panel.

Figure 4-1. Opening the Crystal Structure Prediction Viewer panel.

  1. Open the CSP Viewer from Tasks > Materials > Polymorph Prediction > Crystal Structure Prediction Analysis
  2. Click Load Structures and navigate to where you downloaded the tutorial files and choose Section_04 > CAVVUQ_output_dft_relaxation.maegz file
    • The results will populate into the viewer panel

Figure 4-2. Clicking and viewing the data points.

  1. Click the data points to view information about the structure

Each dot corresponds to one crystal structure and appears as a new entry in the entry list and the packing arrangement is shown in the workspace

Figure 4-3. Viewing the results in data table form.

  1. Go to the Data Table tab
  2. Click Relative Energy to sort the table by relative energy

Scroll across the data table to view information about each crystal structure. There are two known experimental crystal structures and both are found here, highlighted in blue: one has a density of 1.392 and spacegroup P212121 (corresponding to the first row), while the other has a density of 1.338 and spacegroup P212121 (corresponding to the fifth row).

  1. Close the Crystal Structure Prediction Viewer panel

5. Conclusion and References

In this tutorial, we learned how to run the crystal structure prediction workflows for a salt.

For further learning:

For introductory content, focused on navigating the Schrödinger Materials Science interface, an Introduction to Materials Science Maestro tutorial is available. Please visit the materials science training website for access to 100+ tutorials. For scientific inquiries or technical troubleshooting, submit a ticket to our Technical Support Scientists at help@schrodinger.com.

For self-paced, asynchronous, online courses in Materials Science modeling, including access to Schrödinger software, please visit the Schrödinger Online Learning portal on our website.

For some related practice, proceed to explore other relevant tutorials:

For further reading:

6. Glossary of Terms

Entry List - 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

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

Recent actions - This is a list of your recent actions, which you can use to reopen a panel, displayed below the Browse row. (Right-click to delete.)

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 Entry List (and Project Table) and the row for the entry is highlighted. Project operations are performed on all selected entries

Working Directory - the location where files are saved

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