Adsorption of Panthenol on Skin with All-Atom Molecular Dynamics

Tutorial Created with Software Release: 2026-1
Topics: Consumer Packaged Goods, Pharmaceutical Formulations
Methodology: All-Atom Molecular Dynamics
Products Used: Desmond, MS Maestro

Tutorial files

0.79 GB
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, we will study the adsorption of panthenol, a commonly used humectant in cosmetic and pharmaceutical formulations, on a skin lipid bilayer surface using all atom molecular simulations.

 

Tutorial Content

  1. Introduction

  1. Creating Projects and Importing Structures

  1. Building the Panthenol-Water Mixture on the Membrane Interface

  1. Adsorption of Panthenol on Skin Surface using Molecular Dynamics Simulation

  1. Conclusion and References

  1. Glossary of Terms

1. Introduction

The stratum corneum (SC) is the outermost layer of the skin and serves as a primary barrier against environmental irritants, pathogens, and moisture loss. The SC comprises corneocytes (dead keratinocyte cells) packed and surrounded by lipid-rich intercellular spaces. This layer contains lipid bilayers composed of various lipids such as ceramides, fatty acids, and cholesterol. The lipids are arranged into a lamellar structure resembling stacked bilayers. This organization helps form a protective barrier and provides structural integrity to the SC. These lipid bilayers are critical for maintaining skin hydration, and disruptions in the bilayer can lead to compromised barrier function.

Skin moisturizers maintain skin health and appearance by retaining moisture in the skin and keeping it supple. A typical moisturizer formulation contains a variety of substances such as emollients, humectants, occlusives and rejuvenators (see References). Moisturizers also serve therapeutic advantages for dry skin associated dermatoses. Panthenol is commonly used as a moisturizer and humectant in ointments, creams, lotions etc. Panthenol also helps strengthen the skin barrier by acting as an emollient, thus preventing moisture loss from the skin and acts as a protective layer against irritants.

Molecular simulations allow us to probe molecular level properties of atomically resolved models of lipid membranes. In this tutorial, a pre-built all-atom skin lipid bilayer model is adapted from Lundborg et al. (see References) to explore the adsorption of panthenol on the bilayer surface using molecular dynamics simulations. We will observe the adsorption of panthenol on the skin bilayer surface using the Trajectory Density Analysis Calculations panel and plot the intermolecular interaction energy between panthenol and cholesterol to get a quantitative understanding. The overall workflow is depicted below:

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/aa_skin.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 skin_tutorial, click Save
    • The project is now named skin_tutorial.prj

Figure 2-3. Importing structures.

  1. Go to File > Import Structures
  2. Navigate to where you downloaded the tutorial files (presumably in your working directory), and select Builder_molecules.maegz and equilibrated_skin_system-out.cms, click Open

A pre-equilibrated skin bilayer model is provided with the files along with the input molecules used to build the bilayer.

Refer to the Introduction to Materials Science Maestro, Building a Coarse-Grained Skin Model using Martini Force Field and Calculating Surfactant Tilt and Electrostatic Potential of a Bilayer System tutorials to practice preparing the input structures.

Before proceeding to the adsorption study, we will look at the all-atom skin lipids bilayer model in brief. This model is adapted from Lundborg et al. (see References) which was validated with cryogenic electron microscopy (cryo-EM) data for stratum corneum samples. This tutorial uses the “Rank -1” model with a reported periodicity of 10.6 nm. The composition of the lipid bilayer is as follows:

 

The Build Structured Liquid Panel was used to build the lipid bilayer model. The following protocol was followed to relax and equilibrate the membrane using the MD Multistage Workflow panel:

 

  1. 500 ps Brownian minimization at 10 K
  2. 0.1 ns NVT at 303.15 K with position restraints on C, N and O atoms with a force constant of 0.239 kcal/mol A2 (100 kJ/mol nm2) with 1 fs integration timestep.
  3. 5 ns NPT at 303.15 K and 1.01325 bar with a semi-isotropic pressure coupling. Restraints were placed on C atoms of all the lipids with a force constant of 0.0239 kcal/mol A2 (10 kJ/mol nm2) with integration timestep of 1 fs.
  4. 5 ns NPT at 303.15 K and 1.01325 bar semi-isotropic coupling with position restraints on C atoms with a force constant of 0.0048 kcal/mol A2 (2 kJ/mol nm2) and 2 fs integration timestep.
  5. Equilibration for 250 ns NPT at 303.15 K and 1.01325 bar with semi-isotropic pressure coupling and 2 fs integration timestep.

The equilibrated membrane has a periodicity of ~10.4 nm which is close to the value of 10.6 nm reported in literature (Lundborg et al.). This can be seen from the density profile plot as shown below. The peaks in the density correspond to the lipid polar head group region of each leaflet of the bilayer. The 6.5nm peak width is the ceramide rich region and 3.9nm peak width is the cholesterol rich region.


If you would like to build the system yourself, you can use the skin_input.inp input file in the provided skin_input directory to generate the initial membrane structure. The Build Structured Liquid Panel backend utilizes PackMol. Please cite PackMol in any publication that contains results from the use of this panel (see References).

 

3. Building the Panthenol-Water Mixture on the Membrane Interface

In this section, we will use the Disordered System Builder panel to build the panthenol-water mixture interface with the skin membrane.

Figure 3-1. Selecting structures for building the system.

  1. Includethe entry is represented in the Workspace, the circle in the In column is blue the equibrated_skin entry 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 Panthenol and Water entries in the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion.

Figure 3-2. Opening the Disorder System Builder.

  1. Go to Tasks > Materials > Structure Builders > Disordered System

 

Figure 3-3. Setting up the system composition.

  1. Ensure that the Initial State is set to Amorphous
  2. Change Number of molecules to 2172
  3. In the Components table, change the Molecules for Panthenol to 21 and Water to 2151
    • The wt% appears in the panel and the table updates interactively. Here we will use a 10 wt% panthenol composition.
    • The total number of molecules was selected to generate a reasonable size box for an MD simulation

Figure 3-4. Selecting the skin membrane for interface definition.

  1. Check Substrate
  2. For Structure, click Import to select the membrane as the substrate
    • The equilbrated_skin entry appears as the selected structure for the interface
    • If the equilibrated_skin entry does not load, return to the beginning of this section and ensure that you have selected and included the appropriate entries
  3. Choose the Planar interface option from the Substrate type dropdown
  4. Click Define Interface
    • The Define Interface dialog box opens

Figure 3-5. Defining the interface.

  1. For Crystal vector direction, choose c
    • A plane perpendicular to the chosen direction appears in the workspacethe 3D display area in the center of the main window, where molecular structures are displayed
  2. Change the Buffer between surface and components to 1 Å
  3. Change the Buffer between components and surface mirror image in the periodic box to 1 Å
  4. Click OK

 

Note: This allows you to create a gap between the substrate and the disordered system. This is done to prevent any overlaps or unfavorable configurations.

Figure 3-6. Setting up the periodic boundary condition and running jobs.

  1. For Periodic Boundary Conditions (PBC) choose the Use/expand substrate PBC option
  2. Change the job name to disordered_system_skin_panthenol
  3. Adjust the job settings () as needed
    • This job requires a CPU host. The job can be completed in about 10 minutes

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.

 

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_03 > disordered_system_skin_panthenol > disordered_system_skin_panthenol-out.cms file

 

Figure 3-8. Output of the Disordered System Builder in the workspace.

 

After importing or when the job is complete, a new entry group will be incorporated titled MD: disordered_system_skin_panthenol_system (1) containing one entry titled disordered_system_skin_panthenol_all_components_amorphous

  1. Includethe entry is represented in the Workspace, the circle in the In column is blue the new entry
    • The box is visible in the Workspacethe 3D display area in the center of the main window, where molecular structures are displayed
    • The components are colored by default, but feel free to stylize as you wish

4. Adsorption of Panthenol on Skin Surface using Molecular Dynamics Simulation

In this section, we will use the MD Multistage Workflow panel to perform a molecular dynamics simulation on the prepared system. We will use the Trajectory Density Analysis Calculations and Viewer panels to observe the adsorption of panthenol on the skin surface.

Figure 4-1. Opening the MD Multistage Workflow panel.

  1. 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 4-2. Setting up the MD Multistage Workflow panel.

  1. Click Append Stage
  2. Change the next stage (Stage 2) to Molecular Dynamics
  3. Change Simulation time (ns) to 20 ns
  4. Choose NPT as the Ensemble class
  5. Adjust the Temperature to 303.15 K
  6. Click Advanced Options

 

Figure 4-3. Setting up the barostat coupling style.

  1. Choose Semi-isotropic pressure coupling in the Coupling style dropdown options
    • A semi-isotropic or anisotropic pressure coupling is typically recommended for membrane or bilayer simulations.
  2. Click Apply and then OK to close the window

Figure 4-4. Running the molecular dynamics job.

  1. Change the job name to multistage_simulation_skin_panthenol
  2. Adjust the job settings () as needed
    • This job requires a GPU host. The job can be completed in about 2 hours
  3. If you would like to run the job, proceed to click Run. If you would prefer to proceed with imported files, please proceed to the next steps.

 

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_04 > multistage_simulation_skin_panthenol > multistage_simulation_skin_panthenol-out.cms file.  
  3. Close the MD Multistage Workflow panel.

Figure 4-5. Opening the Trajectory Density Analysis Calculations 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 and includethe entry is represented in the Workspace, the circle in the In column is blue the multistage_simulation_skin_panthenol-out (1) entry in the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion
  2. Go to Tasks > Materials > Classical Mechanics > Trajectory Analysis > Trajectory Density Analysis Calculations

 

Figure 4-6. Setting up the Trajectory Density Analysis Calculations panel.

  1. Click Load from Workspace
    • The disordered_system_skin_panthenol_all_components_amorphous is loaded into the panel
  2. For Select atoms for density analysis, use the () icon to access the selection window and click Select

Figure 4-7. Selecting panthenol for density analysis.

  1. Go to the Molecule tab and select Molecule Type as the selection choice
  2. Select UNK - 21
    • This is the selection option for panthenol. For more information on Atom Specification Language (ASL) visit the documentation page.
    • The ASL res.pt “UNK ˮ appears
  3. Click Add and then OK to close the window

Figure 4-8. Setting up panthenol for trajectory density analysis.

  1. Change Selection name to panthenol
  2. Check Center trajectory on this selection
    • Centering the trajectory on a group of atoms eliminates drift of the structures across the cell, which would smear out the time-averaged density in the drift direction.
  3. Click Add Atom Group to add cholesterol for density calculation.

 

Figure 4-9. Setting up and running the job.

  1. Follow steps 20-22 to add res.pt “R1 ˮ as the selection ASL.
    • This is the selection option for cholesterol.
  2. Change Selection name to chol
  3. Change the Job name to trajectory_density_analysis_panthenol
  4. Adjust the job settings () as needed
    • This job requires a CPU host. The job can be completed in a few minutes.
  5. Click Run

Figure 4-10. Opening the Trajectory Density Analysis Viewer panel.

When the job is complete, a new entry group will be incorporated titled MD: disordered_system_skin_panthenol_system (1) containing one entry titled disordered_system_skin_panthenol_all_components_amorphous

  1. Use the WAM button () to open the Trajectory Density Analysis Viewer panel
    • Alternatively, go to Tasks > Materials > Classical Mechanics > Trajectory Analysis > Trajectory Density Analysis Viewer

Figure 4-11. Trajectory Density Analysis Viewer panel.

  1. From the Axis drop down options choose Z

The density profiles for panthenol and cholesterol across the z-axis is shown in the panel. It is evident that the panthenol molecules are distributed over the membrane surfaces and have higher density at the vicinity of the membrane than in the bulk. The cholesterol is distributed between both the leaflets of the membrane bilayer. The slider buttons in the bottom can be adjusted to view the evolution of the density profile with simulation time.

  1. Go to Density Projection tab

Figure 4-12. Viewing the density projection for panthenol.

  1. From the Planes drop down options choose XZ
  2. Choose panthenol from the Selected ASL dropdown options

The projection of the density of panthenol in the xz-plane is shown. Feel free to explore the panel for more analysis.

  1. Close the Trajectory Density Analysis Viewer panel

Figure 4-13. Viewing the trajectory.

 

  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 and includethe entry is represented in the Workspace, the circle in the In column is blue the multistage_simulation_skin_panthenol-out (1) entry in the entry lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion
  2. Double click on the () icon next to this entry
    • The trajectory is now loaded into the workspacethe 3D display area in the center of the main window, where molecular structures are displayed

Figure 4-14. Opening the custom ASL selection menu.

  1. In the Trajectory player, go to Plot menu > Energy Calculations > Custom ASL Sets
    • We can choose a set of molecules to calculate intermolecular and intramolecular interaction energies over the simulation time. This calculation requires a Linux GPU host.

Figure 4-15. ASL selection for panthenol.

  1. For Set name enter panthenol
  2. For ASL enter (res.pt “M1 ˮ)
  3. Click Add Set
    • Panthenol is now added to the selection table for energy calculation. Since cholesterol is a major component in the outer leaflet of the bilayer, we will use cholesterol to define the other interaction set.

Figure 4-16. ASL selection for cholesterol.

  1. For Set name enter chol
  2. For ASL enter (res.pt “R1 ˮ)
  3. Click Add Set
  4. Click OK and close the panel

Figure 4-17. Browsing the configuration file.

  1. Click Browse in the warning dialog box to choose the configuration file to be used for the calculations

Figure 4-18. Opening the configuration file.

  1. Choose the multistage_simulation_skin_panthenol_3-out.cfg file and click Open
  2. In the warning dialog box, click OK
    • This job will take a few minutes on a Linux GPU host

 

Note: Without a Linux host the calculations cannot be performed.

Figure 4-19. Opening the plot window.

When the job is complete, the plot window opens with the calculated energies labeled Energy 1.

  1. Click Energy 1
    • A window opens with the energy plotted over the simulation time

Figure 4-20. Viewing the interaction energy plot.

  1. Check Exclude self terms
    • This will exclude the bonded intramolecular interactions from the plot

The interaction energy between panthenol and cholesterol molecules gradually decreases and reaches a plateau over time. 

  1. Close the window

5. Conclusion and References

In this tutorial, we learned how to study the adsorption of a humectant (panthenol) on the skin membrane surface using all atom molecular dynamics simulations.

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:
  • Packmol: A package for building initial configurations for molecular dynamics simulations. DOI:10.1002/jcc.21224

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

CER NP xx - N-stearoyl phytosphingosine ceramide with xx number of Carbons in the sphingosine moiety

CER NS xx -  N-lignoceroyl sphingosine ceramide with xx number of Carbons in the sphingosine moiety

CER EOS - Omega-O-acyl ceramide

FFA xx - Free Fatty Acid with  xx number of Carbon atoms