[gmx-users] re-equilbrating membrane protein system after g_membed and ligand addition

[Justin A. Lemkul]

Peter C. Lai wrote:
> I was looking at the g_membed paper recently, and noticed the authors "only"
> spent 10ns to re-equilibrate the membedded-system after g_membeding.
> This they also did after bumping the temperature from 300 to 323K "to prevent
> ordering of the bilayer" even though the "typical" simulation temperatures of 
> POPC is 300 to 310K...Anyone know why 323K was used? Was it to compare it
> to the DOPC environment or something?
> 

I can't comment on this, but it seems odd to me, too.

> I noticed for my particular system, I had to run a round of EM on the 
> post-membedded system in order to resolve some clashes before I could mdrun. 
> Then I ran 10ns in NPT with gen_vel=yes at 310K and position restraints on 
> the helix CA atoms. I am inferring that because the membrane patch I used had 
> been previously equilibrated after I constructed it and ran it under NPT at 
> 300K for 100ns, 10ns should be sufficient time to re-equilibrate with the
> protein in the middle and 310K temperature?
> 

I generally find that membrane protein systems need at least 20 ns or so to 
really be equilibrated, but perhaps your system is a bit different.  10 ns is 
about the shortest time you can use to start seeing translational relaxation 
(rotational relaxation of lipids is shorter, roughly 5 ns).

> After the 10ns with protein restrained, I ran Grid_MAT on it and got a 
> reasonable APL (61-62A^2/lipid when taking protein atoms into account,
> comparable to pre-g_membed patch) and the box dimensions look stable. Is
> this sufficient to answer the abvove question?
> 

Could be.  Seems reasonable.

> Now I am going to be introducing a ligand to the protein. Is there a way to 
> preserve any state, like velocities of all the previous atoms? I was thinking
> of the doing the EM while freezing everything but the ligand atoms and 
> allowing the ligand to change conformation (like a docking refinement). After 
> this, can I have the thermostat and barostat rescale the original velocities
> (and gradually heat the ligand) instead of reinitialising everything?
> 

I doubt it.  By introducing new atoms into the system, you can't use a 
checkpoint file any more so you lose the state you had before.  You can preserve 
velocities in a .gro file, but I can't think of a reasonable way to have those 
read (while not having velocities for the ligand) and then heat up the ligand. 
You'd have to use "gen_vel = no" in conjunction with simulated annealing, which 
sounds like a recipe for instability.  Is there any particular reason you think 
a specific set of velocities is required?  Random sampling is all part of 
running proper simulations, so you need multiple, independent states to converge 
to get a reliable result, anyway.

-Justin

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Justin A. Lemkul
Ph.D. Candidate
ICTAS Doctoral Scholar
MILES-IGERT Trainee
Department of Biochemistry
Virginia Tech
Blacksburg, VA
jalemkul[at]vt.edu | (540) 231-9080
http://www.bevanlab.biochem.vt.edu/Pages/Personal/justin

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