Membrane Generating Plugin

Why the plugin? The increase in the computational power over the past few years has allowed for all-atom molecular dynamics (MD) modeling of large biological molecules. Many of these molecules are membrane proteins, which need to be simulated in an appropriate membrane/solvent/ions environment. Since the membrane structure may affect the protein-lipid interactions, which are, in turn, critical for protein function, using the correct structure is imperative. The membrane plugin described here allows to instantly generate biological membrane structures for MD simulations of membrane proteins.

Generating algorithm. The membrane plugin builds a rectangular matrix of the required size out of pre-built membrane square patches. Since biological membranes are lipid bilayers, the patches included two lipid layers, either layer being a 2-dimensional hexagonal lattice of lipids. The lipid tails were (almost) fully extended, allowing for easy inserting proteins (most of which have nearly cylindric shape) into the membrane and, therefore, reducing the required equilibration time. The distance between the layers was set to fit the actual membrane thickness, and the lattice period was set to fit the actual surface density of lipid molecules. Both parameters depended on the lipid type; for many commonly used lipids, these parameters are availbale from experiments (see, e.g., P. R. Rand's page).

To make the generated structure closer to the actual ones, some disorder was introduced into the patches: random orientation of each lipid in the membrane plane, and truncated Gaussian spread in the perpendicular direction. More disorder was caused by a short (1ps) equilibration in vacuum, which eliminated steric collisions among the lipid atoms but left most of lipid tails extended. These features do not complicate inserting proteins into the membrane but additionally reduce the required equilibration time.

Proper head group hydration may be critical for membrane properties and, therefore, for function of membrane proteins. To properly hydrate the lipid head groups, water shells are built around the lipids one by one. Since the solvate plugin can only make use of a pre-equilibrated water box, solvating was done using the Solvate program by H. Gruebmuller. Then water molecules outside the lipid dimensions and inside the hydrophobic layer (there were only a few) were deleted. Therefore, the final patch structure was a slightly disordered lipid bilayer with the lipid head groups solvated.

Plugin usage. The command syntax is simple and consistent with the solvate plugin syntax. Run the following commands in the VMD console:

package require membrane

Running membrane with no arguments gives a short overview of the syntax. For actual generating a membrane, run membrane as follows:

membrane -l <lipid_name> -x <size_in_X> -y <size_in_Y> {-o <output_prefix>}

Replace the contents of the angular brackets with the corresponding parameters:
It takes about 20 seconds to generate an about 100x100A size membrane on a PIII 766MHz laptop. Finally, a caveat: when doing further structural work, make sure your topology file is compatible with the top_all27_prot_lipid.inp topology file included in the membrane plugin. The complete set of the Charmm27 topology and parameter files is available from Alexander MacKerrell's page.