1. Double-click the Materials Science icon
   • (No icon? See Starting Maestro)

Figure 2-1. Change Working Directory option.

2. Go to File > Change Working Directory
3. Find your directory, and click Choose
4. 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/builders_carbohydrate.zip
5. 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.

6. Go to File > Save Project As
7. Change the File name to carb_tutorial, click Save
   • The project is now named carb_tutorial.prj

Figure 3-1. Polymer Builder panel with the Carbohydrate default parameters.

1. Go to Tasks > Materials > Structure Builders > Polymer
   • The Polymer Builder panel opens
2. For Monomer type select Carbohydrate
   • The panel updates to the specialized carbohydrate parameters
3. Leave End Groups as the default: H
4. For amylose, keep alpha-D-Glucose as monomer A, which again is the default
5. Go to the Composition tab

Note: Hydroxyl is also available as an end group selection, if needed. To see which end of the monomer is the head versus the tail, hover over the molecular formula and the 2D Sketch will appear with R1 and R2 labeled for head and tail, respectively

Figure 3-2. Composition tab and running the job.

6. In the Composition tab, set the number of monomers to 12
   • We will construct a 12mer
   • The Total atoms per chain: and Molecular weight: update accordingly

We do not need to change anything in the Chain Growth tab.

7. Change the Job name: to amylose_12mer
8. Adjust the job settings () as needed and click Run
   • This job requires a CPU host and can be completed in a few minutes
9. Close the Polymer Builder panel

Note: The Amorphous Cell tab (typically available in the Polymer Builder panel) is not present when building a carbohydrate. Because carbohydrates are typically modeled in the solution phase, it is best practice to use the Disordered System Builder to construct the model.

Figure 3-3. Updating the style to ball-and-stick.

10. Once the job is incorporated, includethe entry is represented in the Workspace, the circle in the In column is blue poly(alpha-D-Glucose) in the workspacethe 3D display area in the center of the main window, where molecular structures are displayed
11. Go to the Style dropdown and select Apply ball-and-stick representation

Figure 3-4. Amylose 12mer in the workspace.

The amylose 12mer can be visualized in the workspacethe 3D display area in the center of the main window, where molecular structures are displayed. It is constructed with an expected helical structure.

In practice, the 12mer can be used as a component of a more complex simulation box constructed with solvent and/or other molecules with the Disordered System Builder. This will be demonstrated in Section 5 of the tutorial.

Figure 3-5. Cellulose 12mer in the workspace.

Optional: If you’re interested, a model for cellulose can be constructed following the exact same steps, but with beta-D-Glucose as the repeat unit. Unlike amylose, cellulose takes on a substantially more straight structure.

Figure 4-1. Polymer Builder panel.

1. Go to Tasks > Materials > Structure Builders > Polymer
   • The Polymer Builder panel opens
2. For Monomer type select Carbohydrate
   • The panel updates to the specialized carbohydrate parameters
3. Leave End Groups as the default: H
4. Leave alpha-D-Glucose as monomer A, and click Add Monomer
   • A second monomer, B, appears
5. Change the second monomer to beta-D-Glucose from the dropdown menu
6. Go to the Composition tab

Figure 4-2. Composition tab and running the job.

In the Composition tab, Block or periodic copolymer will be selected as default (a result of defining multiple monomers on the Groups tab).

7. For Repeat unit: input AABAA
   • The polymer will be constructed of repeat AABAA units where alpha-D-Glucose is A and beta-D-Glucose is B.
8. For Number of repeat units: input 6
   • The polymer will be composed of 6 AABAA units
   • The Total atoms per chain: and Molecular weight: update accordingly
9. Change the Job name: to carb_copolymer
10. Adjust the job settings () as needed and click Run
    • This job requires a CPU host and can be completed in a few minutes
11. Close the Polymer Builder panel

Figure 4-3. Updating the style to ball-and-stick.

12. Once the job is incorporated, includethe entry is represented in the Workspace, the circle in the In column is blue poly(alpha-D-Glucose-beta-D-Glucose) in the workspacethe 3D display area in the center of the main window, where molecular structures are displayed
13. Go to the Style dropdown and select Apply ball-and-stick representation

Figure 4-4. Newly constructed carbohydrate model in the workspace.

The carbohydrate can be visualized in the workspacethe 3D display area in the center of the main window, where molecular structures are displayed. It is constructed with realistic torsion angles accounting for typical conformations of AA, AB and BA linkages.

Figure 5-1. Creating an Empty Entry.

Because we will use water as a solvent, we must prepare an entry containing a water molecule.

1. Right-click on any empty space in the workspacethe 3D display area in the center of the main window, where molecular structures are displayed
2. Choose Create New Entry > Create Empty Entry

Figure 5-2. Naming the entry.

3. When the Entry title input box appears, input water
   • A new entry is added to the entry list titled water. It does not contain any structure

Figure 5-3. Building a water molecule.

You can generate a water molecule in many ways. Here we will do so quickly with the 3D Builder palette:

4. With the water 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, click on Build
5. In the 3D Builder, click Add Fragments and click the Water molecule (labeled hydroxyl if you hover)
   • A water molecule appears in the workspace
6. Close the 3D Builder palette

Alternatively, use the 2D Sketcher to draw water.

Figure 5-4. Selecting water, including amylose and opening the Disordered System Builder.

Now that we have an entry for the amylose 12mer and water, we can proceed to build a cell in preparation for molecular dynamics. We will construct a cell containing the amylose 12mer immersed in water

7. In the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion, includethe entry is represented in the Workspace, the circle in the In column is blue the amylose 12mer 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 Entry List (and Project Table) and the row for the entry is highlighted. Project operations are performed on all selected entries the water entry
   • Recall that includethe entry is represented in the Workspace, the circle in the In column is blue means to fill the blue circle and visualize the entry in the workspace, while 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 Entry List (and Project Table) and the row for the entry is highlighted. Project operations are performed on all selected entries means to highlight the entry row
8. Go to Tasks > Materials > Structure Builders > Disordered System
   • The Disordered System Builder panel opens
   • Water should be the only component listed in the Components table; if your panel does not match the Figure, repeat the previous step

Figure 5-5. Selecting water, including amylose and opening the Disordered System Builder.

9. Change the Initial state to Tangled chain
   • Because we are immersing the amylose, the tangled chain designation will not apply to it, and will only apply to the water molecules. This is important, because if we wanted to build the amylose into the cell as a traditional component, we should not use Tangled chain, otherwise the well-defined structure prepared with the polymer builder will be obviated in the cell construction.
10. Change the Number of molecules to 10000
11. Check Substrate
12. Ensure that for Structure, Included entry is selected from the dropdown and click Import
    • After clicking Import, poly(alpha-D-Glucose) appears next to the button, indicating that the structure has been loaded into the panel
13. Ensure that the Substrate type is set to Immersed
    • The amylose chain will be immersed in the water molecules
14. Change the Job name to disordered_system_amylose_immersed_water
15. This job will take about 5 minutes on a CPU host. To adjust job settings, click on the gear () button next to the Job name. If you would like to run the job yourself, click Run. Otherwise, import the pregenerated Section_05 > disordered_system_amylose_immersed_water > disordered_system_amylose_immersed_water_system-out.cms file from the provided tutorial files via File > Import Structures
16. Close the Disordered System Builder

Figure 5-6. The cell after running the job or importing and stylizing.

When the job is finished or after importing, a new entry is added to the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion containing the amylose 12mer immersed in water.

For ease of visualization, optionally feel free to stylize the water molecules with wire representation and the amylose chain with CPK representation. Use the Quick Select dropdown in the toolbar to select atoms associated with Solvents, and the Invert button to select all of the non-solvent atoms.

Figure 5-7. Opening the MD Multistage Workflow panel.

Now we will equilibrate the cell with molecular dynamics. We will implement a standard protocol that is described in detail in Section 5 of the Disordered System Building and Molecular Dynamics Multistage Workflow tutorial.

17. 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 Entry List (and Project Table) and the row for the entry is highlighted. Project operations are performed on all selected entries and includethe entry is represented in the Workspace, the circle in the In column is blue the disordered system
18. Use the WAM button () to open the MD Multistage Workflow panel
    • Alternatively, access the panel via Tasks > Materials > Classical Mechanics > MD Simulations > MD Multistage Workflow

Figure 5-8. Setting up the MD Multistage Workflow.

19. Check Relaxation protocol and choose Materials relaxation
20. Change the next stage (Stage 4) to Molecular Dynamics
21. Set the Simulation time (ns) to 10
22. Set the Trajectory Recording interval (ps) to 200
23. Click Append Stage
    • A 5th stage appears in the workflow
24. Change the new stage (Stage 5) to Average Cell
25. Click Append Stage
    • A 6th stage appears in the workflow
26. Change the new stage (Stage 6) to Molecular Dynamics
27. Set the Simulation time (ns) to 10
28. Set the Trajectory Recording interval (ps) to 200
29. Change the Ensemble class to NVT
30. Change the Job name to multistage_simulation_amylose_water
31. Adjust the job settings () as needed
    • This job requires a GPU host. The job can be completed in about 2 hours on a GPU host
32. If you would like to run the job yourself, click Run. Otherwise, import the pre-generated Section_05 > multistage_simulation_amylose_water > multistage_simulation_amylose_water-out.cms file from the provided tutorial files via File > Import Structures
    • MD simulations have a number of files associated with the job, for a full description of each file type see the help documentation on Desmond Files
33. Close the MD Multistage Workflow panel

Figure 5-9. The cell after running the job or importing and stylizing.

When the job is finished or after importing, a new entry is added to the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion containing the system after MD. Feel free to stylize the system as we did before. If you wish, you can view the trajectory.

Notice that the macrostructure remains somewhat helical.

Figure 5-10. Opening the Torsion Profile Analysis panel.

Finally, let’s use the Torsion Profile Analysis and Viewer panels to briefly analyze the distribution of torsions in the amylose structure after the MD simulation.

34. 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 Entry List (and Project Table) and the row for the entry is highlighted. Project operations are performed on all selected entries and includethe entry is represented in the Workspace, the circle in the In column is blue the output system
35. Go to Tasks > Materials > Tools > Torsion Profile Analysis Calculations
    • The Torsion Profile Analysis panel opens

Figure 5-11. Setting up the Torsion Profile Analysis panel.

36. Check Analyze trajectory
    • We will analyze all of the torsions over the course of the 52 frames
37. Click Find Backbone Torsion
    • The panel is populated with (8) unique Torsion SMARTS
    • The calculation is inexpensive, so we can compute the distribution for all of these
    • Because water only has three atoms, there are no torsions associated with solvent
    • Click on Found ## torsions to expand and see the SMARTS for any of the torsions
38. Change the Job name to torsion_analysis_amylose
39. Adjust the job settings () as needed
    • This job requires a CPU host. The job can be completed in about 2 minutes on a CPU host
40. Click Run
41. Close the Torsion Profile Analysis panel

Figure 5-12. Viewing the distribution for one torsion.

When the job is finished, a new entry is added to the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion. The entry is the same as the MD output, but now contains the data for the Torsion Profile Analysis Viewer.

42. Use the WAM button () to open the Torsion Profile Analysis Results panel
    • Alternatively, access the panel via Tasks > Materials > Tools > Torsion Profile Analysis Results
43. On the Torsion Distribution tab, from the Compare Torsions dropdown, choose the following listing: [#8]-[#6]-[#6]-[#8]
    • The left graph updates to show the distribution of torsion angles
44. From the Torsion dropdown, choose the same: [#8]-[#6]-[#6]-[#8]
    • The right graph updates to show the distribution of torsion angles

We can see that the most probable torsions are ~-176˚ and ~-67˚ and ~+60˚  indicating that these are the most energetically favorable at this temperature given the force field.

Figure 5-13. Viewing the torsions in the workspace.

To view the atoms corresponding with any of the bars in the histogram, double-click on a bar and the corresponding atoms will move to be shown in the workspacethe 3D display area in the center of the main window, where molecular structures are displayed.

Feel free to explore the Torsion Distribution tab further. The left graph allows for multiple selection for comparison, while the right graph is for viewing one torsion at a time. Note that the Workspace selection color and Number of bins can be adjusted

Figure 5-14. Viewing the Times Series for a torsion.

When the job is run over the course of a trajectory, we can also view a Time Series:

45. Go to the Time Series tab
46. Choose the [#8]-[#6]-[#6]-[#8] torsion from the Torsion dropdown

The graph shows how each torsion (73 in this case, on the y-axis) changes over time during the trajectory (x-axis), with color-coding indicating the torsion value at that time.

Feel free to explore the Time Series tab further. The Distribution can be plotted here as well as a function of time.