Hi All, I am currently running a MD simulation of a beta barrel protein embedded in a PHPC bilayer (115x2, total 230 lipids). The protein is aligned along the membrane axis i.e. z-axis. However, while running a steered MD (unrestrained) simulation of the protein, I can see that after some time the protein is rotating towards the XY-plane and the protein is tilted by an angle of approximately 20 degrees with the z-axis. The lipid molecules are rotating along with the proteins and tilting slightly about the z-axis in a similar fashion. Is this a regular phenomenon for a membrane protein simulation or am I encountering some kind of artifacts? Any help will be much appreciated.
Hi, it’s really hard to guess whether it’s a physically meaningful event or an artifact of the initial conditions / system preparation. In the latter case, it may be a good idea to keep the protein restrained to let the lipid molecules equilibrate for a few tens of ns. Then run for a few hundred of ns to see what happens.
Thank you for your suggestion. I have run an initial energy minimization of the system followed by five equilibrium simulations with decreasing position restraints on the protein, lipids, each were run for 5 ns. So, after performing 25 ns of position restrained equilibrium simulations I have run the steered MD simulation. The first 100 ns of the steered MD looked fine, but then for the next 20 ns, the protein molecule starts to tilt slightly with respect to the z-axis or membrane axis.
Before you venture with applying external forces (i.e. steered MD) please try to run a few hundred ns of equilibrium MD, to see whether you’re in a free energy minimum at all.