Does Lipid get Displaced Due to Membrane Protein's Open Conformation? Flexible Cell Approach needed?

User discussions
1

GROMACS version:2023.3
GROMACS modification: Yes/No
I’m simulating a membrane protein in its closed conformation within a lipid bilayer system. If the protein opens during the simulation, it will likely displace several lipids towards the boundaries. Given the periodic boundary conditions (PBCs), will this create significant pressure on the lipids? Alternatively, could the lack of space for the lipids to be displaced prevent the protein from transitioning to an open conformation? Is this the rationale behind using the flexible cell approach during MD simulation?

2

With “using the flexible cell approach” do you mean using pressure coupling? If so, then yes, it’s a good idea to do that in general. Otherwise, it’s difficult to get the system density and lipid packing correct. As you say, simulating the opening of a membrane protein without pressure coupling (a flexible simulation cell) will probably not succeed.

3

Hi Magnus,

I should have explained it better. Lets imagine following situation:

Let’s consider a room packed with people, leaving no room for movement. If I want to stretch my hands, I require some space; thus, removing one or two people from the room or expanding room size becomes necessary to accommodate the stretching.

Similarly, within a box brimming with lipids (representing other people), how can a protein undergo conformational changes (similar to stretching hands) if no lipids are removed from the box? The solution lies in either removing some lipids or expanding the box size. Without creating additional space or adjusting the environment, the protein would struggle to achieve its desired conformational alterations within the confined space.

So what is the solution for above condition? Is flexible cell approach (pressure coupling) is used as solution to above situation?

4

Yes, semi-isotropic pressure coupling should address that.