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 input and results files are included for running jobs or examining output. Download the zip file here: schrodinger.com/sites/default/files/s3/release/current/Tutorials/zip/cg_nanoemulsions.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 nanoemulsions_tutorial, click Save
   • The project is now named nanoemulsions_tutorial.prj

Figure 2-3. The entry list after importing.

8. Go to File > Import Structures
9. Navigate to where you downloaded the provided tutorial files, choose input_molecules.mae and click Open
   • A new entry group 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 five entries

Note: Kolliphor was prepared with the Polymer Builder and the rest of the entries were sketched using the 2D Sketcher.

Figure 3-1. Selecting the entries and opening the panel.

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 Entry List (and Project Table) and the row for the entry is highlighted. Project operations are performed on all selected entries all entries in the entry list
2. Go to Tasks > Materials > Classical Mechanics > Coarse Grain Models > Coarse-Grained Force Field Builder
   • The Coarse-Grained Force Field Builder panel opens
3. Click Load Selected Entries
   • The five selected structures are loaded in the panel
4. In the Simulation section, set the Simulation time to 40 ns and the Temperature to 310.15 K
5. 310.15 K is the body temperature
6. Set the Initial density to 0.1 g/cm³
7. Set the Number of molecules to 4127
   • Set the number of kolliphor_EL molecules to 15
   • Set the number of candesartan molecules to 30
   • Set the number of transcutol_P molecules to 50
   • Set the number of capmul_PG-8 molecules to 30
   • Set the number of water molecules to 4002
8. Go to the Map Atoms tab

Note: the composition used here is typical for this type of formulation. The goal is to derive force field parameters on a relatively small system - here we will get a system of ~ 20K atoms - and scale to bigger systems when running DPD simulations. Nevertheless, system size and simulation length for the all-atom run should be set based on the type of system and property of interest, making sure there is enough sampling for the parametrization.

Figure 3-2. Mapping the atoms.

9. Check Use automated CG mapping
   • The automated mapping algorithm will define particles starting from the given all-atom structures given a target particle size (defined by the number of heavy atoms included in a particle) provided by the user. The algorithm penalizes particle definitions that split functional groups and rings as well as penalizes deviations from the target particle size.
   • Manual particle definitions via SMARTS may be inserted in tandem with the automatic mapping.
10. Set the Target particle size to 6
11. Click Initial Auto Map

Figure 3-3. Altering the water auto-mapping.

12. Manually update the water particle to be mapped as 6 molecules to 1 particle
    • Since we have a mixture of particle types and we may want to do a number of studies it is helpful to define a reference particle type, typically the solvent particle type, which is the most present in the system (in this case water). 
13. Set the particle volume to be 180.69 ų/particle
    • At 310.15 K (body temperature), the density of water is 0.99337 g/mL. The volume of a water molecule is given by (molecular weight x 10²⁴ ) / (density * Avogadro’s Number) = 30.115 ų. Our reference volume for particles for the DPD simulation is therefore 6 x 30.115 = 180.69 ų (the mapping scheme that we will use intends to keep particles within a volume range that works well for automatic fitting, ~60-160% of this volume).

Figure 3-4. Viewing the CG mapping scheme

14. Click Show Mapped Molecules
    • This opens a new dialog panel while placing the CG structure in the workspace
15. Choose Mapping on all-atom system
    • The overlapping atoms in the CG structure are displayed in CPK style
16. Click Save Structure to close the panel

This option lets us view the CG mapping scheme to the all-atom structure. We can change the color of the beads, and the structure will update accordingly. Upon closing the dialog, the loaded structure is removed from the workspace and the original structure reappears.

Note: If you are not satisfied with the mapping suggested by the auto-mapping, you can manually modify the particle definitions and refine the mapping using your definitions as pre-defined mapping during the auto-mapping and the Redo Auto Map option.

Figure 3-5. The FF Parameters tab.

17. Go to the FF Parameters tab

The FF (Force Field) Parameters tab is used to specify the parameters that are to be included in the coarse-grained simulation, provide initial values, and fix the values of parameters that do not need to be adjusted.

18. Click Populate Using Structure
    • Parameter types are added based on the all-atom disordered system structure
19. Go to the Nonbonded sub-tab
20. Change the Cutoff distance to 8.1535
    • The cutoff distance is the primary length scale in a DPD simulation. The value chosen should be influenced by the reduced density and the particle volumes, which are displayed on the Map Atoms tab. The cutoff distance should be close to the value of [(reduced density)*(particle volume)]^⅓ for a chosen particle in the system. In this case the W volume was used, as water is our reference particle type.

 

Note: The reduced density is the number of particles within a volume unit of size (cutoff distance)³. The default value of the reduced density, 3.0, is sufficient for the system herein. Larger values of reduced density will increase the accuracy of a DPD model, in particular when fine-grained mapping schemes are used, but at the expense of increased computational intensity. Reduced values smaller than 3.0 are not recommended. Most studies employ values between 3.0 and 5.0.

Figure 3-6. The CG Simulation tab.

The CG (Coarse-Grained) Simulation tab is used to specify the conditions for the coarse-grained production simulations used for fitting the force-field parameters. For each iteration, the CG system is relaxed using a Brownie minimization step, followed by simulations of 100 ps at 10 K and 100 ps at 300 K in the NVT ensemble. Subsequently, the production simulation is performed in the NVT ensemble with the conditions specified in this tab:

 

21. Go to the CG Simulation tab
22. Set the Simulation time to 40 ns
23. Set the Temperature to 310.15 K

Figure 3-7. The Fitting tab and running the job.

The Fitting tab is used to specify the parameters for fitting the force field from the coarse-grained simulation results.

24. Go to the Fitting tab
25. Change the Iterations to 80
    • Note in more complex systems, the fitting will benefit from more iterations
26. Change the Job name to cgff_builder_emulsion
    • Adjust the job settings () as needed. This job requires a GPU host. The job can be completed in about 1 day on a single GPU.
27. Close the Coarse-Grained Force Field Builder panel and let’s proceed with pre-generated files

Figure 4-1. The output of the force field builder.

If you ran the job, the output will automatically incorporate, producing an entry titled amorphous_cg. Otherwise:

1. To import the results, go to File > Import Structures, navigate to the provided tutorial files and choose Section_04 > cgff_builder_emulsion > cgff_builder_emulsion-out.cms
   • An entry is added to the entry list titled amorphous_cg
   • The entry contains the final cell from the final coarse-grained simulation

Figure 4-2. Builder Data tab

We can assess the quality of the fit using the Coarse Grain Forcefield Builder viewer panel.

2. Use the Workflow Action Menu (WAM) button () or go to Tasks > Materials > Classical Mechanics > Coarse Grain Models > Coarse-Grained Force Field Builder Results
   • The Coarse Grain Forcefield Builder Viewer panel opens
   • If the panel is not populated by default, click Load from Workspace

 

The Builder Data tab contains information about the input parameters.

Figure 4-3. Fit Quality tab: nonbonds, R-squared.

3. Go to the Fit Quality tab

The fit quality tab provides R-squared values for the quality of the fit as a function of iteration. It also contains a tab for viewing plots.

The nonbonds are displayed first. The data describe the pair distribution functions and their integrals for each non-bonded interaction in the CG system.

This data helps you understand how well the non-bonded parameters in the CG model reproduce the non-bonded interactions in the all-atom system. The coefficient of determination (R²), can be used to flag those interactions that might need a closer investigation and potentially an improvement.To understand if the fit is good enough, it is always best to check how the radial distribution functions (RDFs) and their integrals compare between atomistic and DPD runs.. They are available under the Plot Tab. Comparison between the RDFs is useful to understand if the frequency of interaction between the defined particles in the atomistic run is enough or if an improvement in the sampling is needed. Comparison between the integrals of the RDF at the cutoff value is more indicative of the quality of the fitting.

Note: Changing the Iterations to display and Number of profiles to display options at the bottom of the panel can change the granularity of the data output.

To learn more about analyzing the force field parameters see the Automated Dissipative Particle Dynamics (DPD) Parametrization tutorial.

4. Set the Number of profiles to display to 4
   • This will make the results more user friendly to view
5. Click Save Forcefield Data…
6. Name the new forcefield nanoemulsion
   • You can also merge with a pre-existing force field if you are improving on a past effort
7. Click OK to close the panel
8. Close the Coarse Grain Forcefield Builder Viewer panel once finished

Figure 4-4. Inspecting the .json file.

The cgff_builder_emulsion-out_cgff.json file contains the final force field parameters from the automated procedure. It can be accessed from the output directory.

The output directory also contains a file mapped_cg_structures.maegz with individual input structures for the separate system components. These can be used to construct new systems of various concentrations and we will import this file in the next section. 

Figure 5-1. Importing the five components.

Before constructing a hydrated system, we need coarse-grained entries of the individual components in the entry list.

1. Go to File > Import Structures
2. Navigate to where you downloaded the provided tutorial files, choose Section_04 > cgff_builder_emulsion > mapped_cg_structures.maegz and click Open
   • A new entry group 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 five entries
   • The entry names correspond to the mapping nomenclature

Figure 5-2. Renaming the components.

3. Rename the entries to better correspond to the components name for ease
   • (A1)(B1)(C1)(D1)(E1) → candesartan_cg
   • (A4)(B4) → capmul_PG-8_cg
   • (A2)(B2) → transcutol_P_cg
   • (W) → water_cg
   • (A3)3(B3)3(C3)3(D3)18(E3) → kolliphor_el_cg

Figure 5-3. Opening the Disordered System Builder panel.

4. Ensure that the entire mapped_cg_structures entry group is 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 from the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion
5. Go to Tasks > Materials > Structure Builders > Disordered System
   • The Disordered System Builder panel opens
   • The selected components are by default loaded into the panel
6. Click OK to any warnings about the force field
   • We will apply the force field after constructing the system

Figure 5-4. Setting the number of molecules.

7. For Initial state, choose Tangled chain
8. Change Number of molecules to 143045
9. In the Components table, change the Molecules for each component to:
   • candesartan_cg → 65
   • capmul_PG-8_cg → 7823
   • transcutol_P_cg → 212
   • water_cg → 134533
   • kolliphor_el_cg → 412
10. Select Create new cubic PBC for the Periodic Boundary Conditions (PBC)
11. Go to the Disorder tab

Figure 5-5. Naming the calculation.

12. Uncheck Color molecules by component
13. Set the Initial density to 0.200
14. Change the Job name to disordered_system_hydrated_emulsion
15. Adjust the job settings () as needed
    • This job requires a CPU host and can be completed in about 1 day
16. If you would like to run the job yourself, click Run. Otherwise, we’ll proceed with pre-generated files.
17. Close the Disordered System Builder panel

Figure 5-6. Viewing the disordered system.

18. To import the results, go to File > Import Structures, navigate to the provided tutorial files and choose Section_05 > disordered_system_hydrated_emulsion > disordered_system_hydrated_emulsion_amorphous.maegz.

The Figure shows the output of the Disordered System builder with water particles hidden.

Figure 5-7. Opening the Coarse-Grained Force Field Assignment panel.

Remember that these coarse-grained systems have not yet been assigned a force field. We must do so now with the Coarse-Grained Force Field Assignment panel

19. Go to Tasks > Materials > Classical Mechanics > Coarse Grain Models > Coarse-Grained Force Field Assignment
    • The Coarse-Grained Force Field Assignment panel opens

 

Note: Please BE PATIENT when waiting for the panel to open. It must read all of the coarse-grained particles into the panel and can take several minutes.

 

20. Select nanoemulsion for Import force field
21. Set the Location to Local
22. Click Import to apply the force field to the system
    • Click OK to any questions, we will reconcile them next

 

Scan through the Site, Bond, Angle and Nonbond tabs. All of the parameters from our fitting procedure populate the panel.

Figure 5-8. Running the Coarse-Grained Force Field Assignment panel.

23. Go to the Nonbond tab
24. Ensure that the Reduced Density is set to 3.000 (per our original decision) and the cutoff distance set to 8.1535
25. Click Run
    • Click continue if any messages appear
    • Again, it can take up to a minute to apply the force field and then the panel will close automatically
    • Feel free to rename the Desmond input file that will be created to something shorter

 

Figure 5-9. Viewing the Coarse-Grained Force Field Assignment panel results.

A new entry will appear in the entry list. This entry is ready for a MD simulation.

 

Note: The cell parameters have been automatically rescaled by the Coarse-Grained Force Field Assignment panel, to match the target Reduced Density of 3.

Figure 6-1. Opening the MD Multistage Workflow panel.

1. Use the WAM (workflow action menu) button () to open the MD Multistage Workflow panel
   • Alternatively, access the panel via Tasks > Materials > Classical Mechanics > MD Simulations > MD Multistage Workflow
   • The MD Multistage Workflow panel opens

Figure 6-2. Running the MD simulation.

2. Check Relaxation protocol and choose Repulsive harmonic
3. Change the next stage (Stage 4) to DPD Molecular Dynamics

• When running simulations with repulsive potentials like in DPD, the NVT ensemble ensures that the target Reduced Density is maintained.

4. Set the Simulation time (ns) to 250
5. Set the Trajectory Recording interval (ps) to 1000
   • This will generate about 250 frames in the trajectory
6. Set the Temperature to 310.15
7. Set the Time step (fs) to 10
8. Change the Job name to md_hydrated emulsion
9. Adjust the job settings () as needed
   • This job requires a GPU host and can be completed in about 10 hours
10. If you would like to run the job yourself, click Run. Otherwise, we’ll proceed with pre-generated files.
11. Close the MD Multistage Workflow panel

Figure 6-3. Viewing the MD output structure.

If you ran the job, the output will automatically incorporate, producing an entry. Otherwise:

12. To import the results, go to File > Import Structures, navigate to the provided tutorial files and choose Section_06 > md_hydrated_emulsion > md_hydrated_emulsion-out.cms

 

 

 

Figure 6-4. Viewing the MD trajectory.

13. Double click the blue T trajectory button
    • Due to the size of the system the trajectory could take a moment to load
14. Click the play button to view the trajectory

 

The trajectory shows that initially the system is a homogeneous mixture but then as the simulation progresses candesartan and kolliphor EL migrate together. Feel free to explore the trajectory and the system.