Populating Lipid Layers Around Proteins in 3D: A Practical Guide

Building biologically realistic environments around membrane proteins is a regular challenge for molecular modelers. From preparing lipid bilayers to ensuring correct spatial orientation, the process often involves high manual overhead and repetitive trial and error. If you’ve ever struggled with these tasks, the Molecular Box Builder extension in SAMSON might simplify your workflow considerably.

In this post, we’ll walk through a practical use case: building a lipid layer around a membrane protein. This is a task that can usually take time to manually configure, but it can now be done visually and interactively, directly from within SAMSON.

Goal

We’ll demonstrate how to insert a custom lipid layer around a protein structure, avoiding overlaps and ensuring correct alignment, using the Molecular Box Builder. As an example, we’ll use the copper-transporting PIB-ATPase (4BBJ), but you can adapt the procedure to any protein of interest.

Step 1: Align the Protein

To ensure the lipid layer forms properly around the membrane-spanning region, you’ll first want to orient the protein so that its membrane axis points along Z:

  1. Right-click your protein in the Document view.
  2. Select Move selection > Align with Z axis.
  3. Then choose Move selection > Center on the origin.

Align protein

Step 2: Define the Lipid

Next, import your lipid structure. You can bring in a single molecule (e.g. POPC or any custom lipid), and define it as the building block for creating the layer:

  1. Select the lipid molecule.
  2. In the Molecular Box Builder, click Set.
  3. Align the lipid’s main axis to +Z to match the membrane orientation.

Align a molecule with Z-axis

Step 3: Create the Box

Now, it’s time to define the spatial dimensions for your lipid layer. In Molecular Box Builder:

  1. Center the box on the protein structure using the Center option.
  2. Adjust box dimensions to span the X and Y directions for layer coverage, and a limited range in Z to create a monolayer.
  3. If needed, tweak the margin values to prevent overlapping lipids.

A box with a protein

Step 4: Generate the Lipid Layer

Before generating, enable the option Consider existing molecules in the box. This ensures lipids are placed only in the available space and prevents overlaps with the protein.

  1. After alignment and box setup, click Generate.

You should now have a monolayer of lipids surrounding your protein model:

A lipid layer with a protein

Creating a Bilayer (Optional)

For a full bilayer, repeat the generation for a second layer with the lipid aligned to -Z and shift the box position accordingly. You can generate realistic bilayers suitable for simulation by doing this step twice.

Use Cases and Advantages

Whether you’re preparing configuration files for MD simulation or designing biomimetic materials, having a way to visually and interactively create lipid-protein systems can save time and reduce guesswork. You can export the resulting system and proceed to minimization and simulation using tools like the GROMACS Wizard.

Learn more about the full procedure and advanced options in the Molecular Box Builder tutorial.

SAMSON and all SAMSON Extensions are free for non-commercial use. You can get SAMSON at www.samson-connect.net.

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