Building a Coarse-Grained Surfactant Model with Martini Force Field

Tutorial Created with Software Release: 2025-4
Topics: Consumer Packaged Goods, Pharmaceutical Formulations, Polymeric Materials
Methodology: Coarse-Grained Modeling
Products Used: Desmond, MS CG, MS Maestro

Tutorial files

45 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:

 

This tutorial demonstrates how to build a coarse-grained surfactant molecule and construct an amorphous cell containing surfactant molecules in water with assigned Martini force field parameters. Then, a molecular dynamics simulation is run to visualize formation of a liquid crystalline phase. Finally, we calculate the radial distribution function for the equilibrated cell.

 

Tutorial Content

  1. Introduction to Coarse-Grained Modeling with Martini Force Field

  1. Creating Projects and Importing Structures

  1. Generating Coarse-Grained Molecules

  1. Applying a Coarse-Grained Force Field

  1. Setting Up a Multistage Simulation Workflow

  1. Calculating the Radial Distribution Function

  1. Conclusion and References

  1. Glossary of Terms

1. Introduction to Coarse-Grained Modeling with Martini Force Field

A coarse-grained model represents molecules or portions of molecules using particles (sometimes referred to as beads), each of which corresponds to a number of atoms. The desired mapping of the all-atom system to the coarse-grained can be determined by evaluation of model goals and the underlying molecular system. To build coarse-grained models, the desired mapping must be known, as well as all associated parameters. The coarse-grained molecular dynamics (MD) technique is commonly used for polymers, soft matter, and various complex formulations, particularly when the system sizes or time simulated become too large to use atomistic models.

With surfactant modeling, atomistic simulation can struggle to reach the length and time scales necessary for self-assembly. Coarse-grained methods can help more easily access these length and time scales (see References). Poly(oxyethylene) alkyl ethers, [CH3(CH2)i-1(OCH2CH2)jOH], usually abbreviated CiEj are nonionic surfactants composed of a hydrophobic alkyl chain and hydrophilic oxyethylene units. CiEj surfactants solvated with water exhibit a rich phase behavior, in particular, C12E2 with 70 wt% produces the lamellar configuration.

In this tutorial, we will reproduce the lamellar configuration of C12E2 in water using a coarse-grained approach with the Martini force field. The Martini force field, one of the most widely used force fields for these types of systems, can be applied to the coarse-grained structure.  Martini force field parameters can be obtained or adapted for many molecules from the literature (note there are 100's of articles). If novel molecules are being used as an initial step, it is often helpful to assign initial guesses for appropriate Martini site types using experimental logP values.  Please consult Selecting Martini Parameters in the help documentation for suggestions on how to proceed.  In the end, comparison of simulation results for small systems with experimental behaviors of interest is a good way to check parametrization and gain insight into what refinements may be needed.

The coarse-grained structure that we will use of C12E2 is as follows:

For Martini models, one tries to have sites that represent ~4 heavy atoms along with their bound hydrogen atoms. In addition, ideally, we do not want to split functional groups. The parameters for this coarse-grained structure for C12E2 can be found in the literature in a report by G. Rossi et. al (J. Phys. Chem. B 2012, 116, 14353). All of the potential terms can be obtained based on relation to known parameters (Guess), an average of bonded atomistic interaction (Average), user input based on supplied information (Edited) or from a database of known parameters (Database). This tutorial will use Database parameters.

In this tutorial, we will use various panels in the Materials Science (MS) Maestro interface. For the corresponding help documentation, see Coarse-Grained Sketcher, Disordered System Builder, Coarse-Grained Force Field Assignment, MD Multistage Workflow and Radial Distribution Function.

In addition to the panel help documentation, we recommend visiting the overview of Coarse-Grained Modeling in the Materials Science Suite. For this tutorial, it is recommended to read Potentials and Simulation Types for Coarse-Grained Modeling, Coarse-Grained Modeling with the Martini Force Field, Selecting Martini Parameters, and Site Types for Martini

While this tutorial covers surfactant modeling with a coarse-grained approach, educational materials are also available for studying related systems with an all-atom approach. See the Cluster Analysis and Calculating Surfactant Tilt and Electrostatic Potential of a Bilayer System tutorials.

In general, using all-atom versus coarse-grained approaches depends on the goals of your work, and some experimentation is very typical.

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, find your directory, and click Choose
  2. 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/peg_coarsegrained_martini.zip
  3. 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. Saving the project.

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

3. Generating Coarse-Grained Molecules

In this section, we will use the Coarse-Grained Sketcher and Disordered System Builder to prepare a starting model for the system. The coarse-grained sketcher is a tool for drawing a coarse-grained structure in 2D and saving it as a project entry. Note that the structure is strictly 2D - unlike the 2D Sketcher - no conversion to 3D is done when the structure is saved, and the placement of particles with their interparticle distances is preserved. For a more in depth explanation of building disordered systems, see the Disordered System Building and Molecular Dynamics Multistage Workflows tutorial.

Figure 3-1. Define Force field file.

  1. Go to Tasks > Materials > Classical Mechanics > Coarse Grain Models > Coarse-Grained Sketcher
  2. For Use particle types from, choose Force field file and click Create

Figure 3-2. Apply Martini force field.

  1. In Location, check Installation option
    • A list of particle types to create appear
  2. From the list, select then click Add particle types BUT, PEO_SP0, PEO_SPh, W and WF types
    • The types appear in the Particle types to be created dialog box
    • These groups correspond with those used in the report by G. Rossi et. al. On the whole, we want groups that have roughly 4 heavy atoms and their attached H atoms. As much as reasonable, we want the groups to have similar volumes in solution
  3. Click OK

Figure 3-3. Coarse-Grained Sketcher with five spheres.

Five spheres appear in the Coarse-Grained Sketcher

  • BUT stands for butane and C1 is the Martini type for it
  • PEO stands for Polyethylene oxide and the SP0 is the Martini type for it
  • SPh Martini type is assigned to the terminal CH2-OH group of C12E2 chain.
  • W is the Martini type for water
  • WF is another Martini type for water

 

Note: Bead colors can be changed. Right-click on the bead you want to change color. Click Edit Particle… and select a different color of your choice in Color.

 

Note: We recommend using a commonly employed option in the Martini force field of two types of water particles (W and WF) to reduce the chance that the solvent particles might freeze.

Figure 3-4. Sketch C12E2 chain.

  1. Click and drag in the Sketcher to connect three BUT sites (black sphere)
  2. Select a PEO_SP0 type (first green sphere) and drag two more beads connecting them to a terminal BUT bead
  3. Connect PEO_SPh type (second green sphere) to the PEO_SP0 to obtain a C12E2 coarse grained structure
  4. For Title, input C12E2
  5. Click Create Project Entry
    • The C12E2 coarse grained surfactant is added to the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion.

Figure 3-5. Sketch W bead.

  1. In the Coarse-Grained Sketcher, click the reset button () in the lower left-hand corner
    • The Sketcher and Title are cleared
  2. Select a W type and place one bead in the coarse-grained sketcher field
  3. Next to Title, input water
  4. Click Create Project Entry
    • Water is added to the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion.. It is includedthe entry is represented in the Workspace, the circle in the In column is blue. and selectedthe entry is chosen in the Entry List (and Project Table), the row is highlighted; project operations are performed on all selected entries. in the workspacethe 3D display area in the center of the main window, where molecular structures are displayed.

Figure 3-6. Sketch WF bead.

  1. Click the reset button
  2. Add a WF bead in the sketcher field
  3. Next to Title, input waterF
  4. Click Create Project Entry
    • Water is added to the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion.. It is includedthe entry is represented in the Workspace, the circle in the In column is blue. and selectedthe entry is chosen in the Entry List (and Project Table), the row is highlighted; project operations are performed on all selected entries. in the workspacethe 3D display area in the center of the main window, where molecular structures are displayed.

 

 

Note: WF will be used to represent 10% of all water molecules (established in upcoming steps) to avoid water crystallization, as discussed above

Figure 3-7. The updated entry list.

  1. Close the Coarse Grained Sketcher
    • Three different molecules (C12E2, Water and WaterF) have been added to the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion.

Figure 3-8. Selecting all the entries and opening the Disordered System Builder.

  1. Selectthe entry is chosen in the Entry List (and Project Table), the row is highlighted; project operations are performed on all selected entries. all three structures from the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion. with Shift+Click
  2. Go to Tasks > Materials > Structure Builders > Disordered System
    • Click OK to the warning. The force field will be applied at a later step
    • The Disordered System Builder opens with the three components matching the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion.

Figure 3-9. Disordered System Builder: Components.

  1. For Initial state, check Tangled chain
    • Visit the documentation for the differences between the choices. Typically, tangled chain allows for the quickest build
  2. For Number of molecules, input 1112
  3. In the Molecules column set 431 for C12E2, 612 for Water and 69 for WaterF
  4. For Periodic Boundary Conditions (PBC), choose Create new cubic PBC

 

The first % column indicates the percent of molecules. The quantities update dynamically.

 

According to the paper of Rossi et. al (J. Phys. Chem. B 2012, 116, 14353) C12E2 represents 70 wt % of the solution. 431 C12E2 molecules are used which collectively weigh 274x431 AMU. Water should represent 30 wt%, i.e. water weight = (weight of C12E2) *(100/70) * (30/100) = 25365 g/mol. The weight of a Martini water bead is 72 g/mol. This means 681 Martini Water molecules should be present in the solution.  However, antifreeze water (WF) makes Martini water a little less dense thus we used slightly fewer water molecules: 612.  

Figure 3-10. Disordered System Builder: Disorder.

  1. Go to Disorder tab
  2. Set Initial VdW scale factor to 0.7
  3. Uncheck Color molecules by component
  4. Change the Job name to disordered_system_C12E2_in_water
  5. Click Run
    • This job takes <5 minutes on a local CPU host
  6. Close the Disordered System Builder

Figure 3-11. Select and include the unit cell.

 

Once the job is complete, in the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion., selectthe entry is chosen in the Entry List (and Project Table), the row 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 new entry disordered_system_C12E2_in_water_all_components_amorphous

 

The file is also available for importing from the provided tutorial files: Section_03 > disordered_system_C12E2_in_water > disordered_system_C12E2_in_water_amorphous.maegz

 

Note: If the unit cell box is not displayed, toggle it on by clicking Unit Cell in the Workspace Configuration Toolbar ()

4. Applying a Coarse-Grained Force Field

Now, the Martini force field can be applied to the coarse-grained unit cell created in the previous section using the Coarse-Grained Force Field Assignment panel. In this tutorial, we will use Database parameters.

Figure 4-1. Assign the force field to the C12E2 amorphous cell.

  1. Go to Tasks > Materials >  Classical Mechanics > Coarse Grain Models > Coarse-Grained Force Field Assignment
    • The Coarse-Grained Force Field Assignment panel opens
  2. For Location, check the Installation option
    • This will import the provided Martini force field from the standard directory of the software installation. This includes the parameters needed for these particles assignments
  3. Click Import
  4. Click OK on the warning message to continue enumerating types
    • All of the Martini force field parameters are automatically assigned to all of the beads

Figure 4-2. Running the force field assignment.

Skim through the various parameters. Here we use Bond, Angle and Nonbond parameters which are available in the Martini database that comes with the Schrödinger installation.

 

  1. Click Run to finalize the force field typing
    • This job takes a few seconds
    • A banner appears when the job has been incorporated
    • A new group titled Coarse-Grained Force Field Assignment (1) with a new entry titled disordered_system_C12E2_in_water_all_components_amorphous is added to the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion.. It is includedthe entry is represented in the Workspace, the circle in the In column is blue. and selectedthe entry is chosen in the Entry List (and Project Table), the row is highlighted; project operations are performed on all selected entries. in the workspacethe 3D display area in the center of the main window, where molecular structures are displayed.  

Note: The panel should be closed after force field assignment to prevent slow response in MS Maestro for subsequent operations.

Figure 4-3. Output in the entry list and workspace.

The output will exactly match the previous structure, but will now be a .cms file-type including the force field parameters in preparation for molecular dynamics

5. Setting Up a Multistage Simulation Workflow

Now that we have force-field typed our system, we are ready to proceed to a molecular dynamics (MD) simulation using the MD Multistage Workflow panel. For a more in depth explanation of building disordered systems, see the Disordered System Building and Molecular Dynamics Multistage Workflows tutorial.

Figure 5-1. Preparing the MD Multistage Workflow.

  1. In the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion., selectthe entry is chosen in the Entry List (and Project Table), the row 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 new entry disordered_system_C12E2_in_water_all_components_amorphous
  2. Go to Tasks > Materials > Classical Mechanics > MD Simulations > MD Multistage Workflow
    • The MD Multistage Workflow panel opens
    • The panel can also be conveniently accessed using the Workflow Action Menu button () directly from the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion.
  3. For Use structures from, choose Workspace (1 included entry)
  4. Check Relaxation protocol and maintain the default Martini protocol for equilibration
  5. For (7) Stage Type select Martini Molecular Dynamics
  6. Set Simulation time to 100 ns
  7. Set Recording interval for Trajectory to 200 ps
  8. Set Recording interval for Energy to 50 ps
  9. Set Time step to 10 fs
  10. Click Advanced Options

Figure 5-2. Ensemble Advanced options.

  1. In the Ensemble tab, maintain Langevin ensemble for both Thermostat and Barostat
  2. Maintain the Relaxation time to 10 ps for the Thermostat
  3. Set the Relaxation time to 20 ps for the Barostat
  4. Choose Anisotropic Coupling style for the barostat method
  5. Click Apply and then OK to close the Advanced tab

Regarding the choices for the MD parameters:

  • From performing a few trials, 100 ns proved to be sufficient for the system to order  
  • The recording interval settings are pragmatic to keep the file sizes relatively small
  • The time step is the minimal time step size that is ‘safe’ for Martini 
    • Martini systems, particularly during equilibration, can change size quickly in NPT. This can cause numeric problems and crashes if the time step is larger than 10 fs
    • Langevin dynamics is more robust to large energy inflows than Martyna-Tobias-Klein, so that is suggested here
    • Setting the Thermostat to a smaller Tau value helps a bit (and lets the system evolve faster); however, setting the barostat relaxation time to a larger value (50 ps may be even better here) slows the volume change rate down. Together these settings usually permit stable simulations with a 30 fs timestep 
  • Anisotropic coupling is good for this system since the layer spacing for the surfactants may not coincide well with the box size/shape.  Letting it change can let the system select a box shape that is compatible with the periodicities present

Figure 5-3. Naming and running the job.

  1. Back in the MD Multistage Workflow panel, input the Job name: multistage_simulation_C12E2-100nsNPTat300K
  2. Adjust the job settings () as needed
    • This job requires a GPU host.
    • If you would like to run the job, click Run. If you would prefer to proceed with imported files, please proceed to the next steps.
  3. Close the MD Multistage Workflow panel

Figure 5-4. Importing the pre-generated file.

 

We will assume that you have not run the calculation, and instruct for importing:

  1. Go to File > Import Structures
  2. Navigate to where you downloaded the tutorial files and choose the Section_05 > multistage_simulation_C12E2-100nsNPTat300K > multistage_simulation_C12E2-100nsNPTat300K-out.cms file

Figure 5-5. View the trajectory.

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. titled disordered_system_C12E2_in_water_all_components_amorphous

 

  1. Selectthe entry is chosen in the Entry List (and Project Table), the row 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 new entry and Double-Click the to view the trajectory
    • The Trajectory Viewer appears

 

  1. Click Play
    • The expected phase separation between water and surfactant is confirmed. This is a lamellar configuration

 

Feel free to pause the trajectory and rotate the unit cell in the workspacethe 3D display area in the center of the main window, where molecular structures are displayed. to best visualize the phase separation.

 

  1. Once complete, close the Trajectory Viewer using the () button in the top-right corner of the Trajectory Viewer (in the bottom right corner of the workspacethe 3D display area in the center of the main window, where molecular structures are displayed.)

6. Calculating the Radial Distribution Function

Finally, we can analyze the output with the Radial Distribution Function panel. We use radial distribution functions to help understand what groups are preferentially associating with each other. This function can provide numeric representations for this.

Figure 6-1. Load an MD structure into the RDF panel.

  1. Go to Tasks > Materials > Classical Mechanics > Trajectory Analysis > Radial Distribution Function
  2. In the Trajectory source dropdown menu select File
  3. Click Import… and navigate to where you downloaded the tutorial files and choose multistage_simulation_C12E2-100nsNPTat300K-out.cms
    You should see the file name populate next to the Import button
  4. Click Open
    • Note that in the workspacethe 3D display area in the center of the main window, where molecular structures are displayed. and entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion., another copy of the output system will load

Figure 6-2. Histogram RDF options.

  1. At the bottom of the panel set Max distance for RDF (max r) to 25.00 Å (less than half of the min unit cell length)

Figure 6-3. Select SPh beads.

The RDF can be built between two sets of molecules. As an example, the RDF between PEO_SPh beads and water will be built. In order to do so, the set of SPh beads should be selected first.

 

  1. In the RDF panel click the Select button associated with Set 1
    • The Atom Selection panel opens
  2. Select Atom name in the properties table and PEO_SPh Atom name
    • Note that coarse-grained particles are treated as ‘atoms’ in the atom selection panel
  3. Click the Add button to make the selection
  4. Click the OK button to pass the selection to the RDF panel  

Figure 6-4. Select Water beads.

  1. Check Set 2 in the RDF panel
  2. Click the Select button associated with Selection 2 to open an Atom Selection panel
  3. Select Atom name in the properties table and W Atom name
  4. Click the Add button to make the selection
  5. Click the OK button to pass the selection to the RDF panel

Figure 6-5. Set the Job name and run.

  1. Set the Job name to rdf_SPh-W
  2. Click Run

 

Do not close the panel - this job takes about a minute. Once the job is complete, the panel will automatically switch to the View Results tab and a histogram of the RDF will appear

 

Note: If you do close the panel, or to reload results at a later time, use the Import Results File option on the View Results tab.

Figure 6-6. The Radial Distribution Function.

The RDF shows typical liquid structure with the prominent peak for the first nearest neighbors and less noticeable peaks for the second and more distant neighbors.

7. Conclusion and References

In this tutorial, we completed a workflow to build a random structure of coarse-grained surfactant chains in water. The Martini force field was applied. A short coarse-grained molecular dynamics run resulted in a lamellar phase of the PEG surfactant solvated in water as expected. 

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.

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

For further reading:

8. 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.

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 - the entry is chosen in the Entry List (and Project Table), the row 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.