Creating lipid layers around proteins can be a time-consuming challenge for molecular modelers. From aligning your structure to meticulously placing lipids, it’s often a painstaking process. Thankfully, Molecular Box Builder in SAMSON streamlines this, making it easier and faster to create uniform lipid layers—or even a lipid bilayer—around your protein of interest.
Reorienting the Protein: A Critical First Step
Before generating a lipid layer, properly orienting your protein ensures accurate placement of lipids. Start by centering and aligning your protein in SAMSON:
- Right-click the protein in the Document view.
- Select Move selection > Align with Z axis from the context menu.
- Then, choose Move selection > Center on the origin.
This alignment simplifies the process of ensuring that the lipid layer will uniformly surround your protein.

Step 2: Assigning the Lipid Molecule
A well-oriented lipid molecule is the foundation of your lipid layer. Here’s how to set it up:
- Import a lipid molecule into SAMSON.
- Select the lipid and click Set in the app.
- Align its principal axis to the
+Zdirection. This alignment ensures a structured organization of the lipid molecules in the layer.

Step 3: Configuring the Lipid Layer Box
Now comes the part where your pocket of imagination takes shape around the protein:
- Center the box around your protein using the app’s Center function.
- Adjust the box’s size to encapsulate a single lipid layer. This ensures the protein is embedded comfortably within the lipid layer.
- If needed, specify a margin between lipid molecules to refine packing density or address potential clashes. Aim for uniformity to create a stable configuration.

Step 4: Generating the Lipid Layer
The most gratifying step of the process is the generation of the lipid layer itself. Before proceeding:
- Toggle Consider existing molecules in the box within the app. This feature ensures lipids are only added where space permits, avoiding overlaps with the protein or existing molecules.
- Click Generate. In seconds, you’ll witness a perfectly aligned lipid layer around your protein.

Creating a Lipid Bilayer (Optional)
To generate a full lipid bilayer around your protein, repeat the following steps:
- Add the first layer with lipids aligned to
+Z. - Shift the box’s center slightly along the
Zaxis. - Add the second layer of lipids, this time aligned to
-Z.
Within minutes, you’ll create not just a single lipid layer, but an entire bilayer that dynamically interacts with your protein during further simulations.
Next Steps
After constructing your lipid-protein system, you’re ready to minimize, equilibrate, and simulate. Use the GROMACS Wizard for energy minimization and simulations, ensuring realistic behavior of your system.
For a more detailed step-by-step breakdown of this workflow, visit the official documentation.
SAMSON and all SAMSON Extensions are free for non-commercial use. Download SAMSON today at www.samson-connect.net.
