Re: Membrane Protein Simulation Problems

From: Richard Law (
Date: Sat Oct 13 2007 - 03:05:02 CDT

You seem to have done a lot of things right. (I haven't actually worked with
POPE but I'll assume that that isn't an issue).

What is the protein - i.e. is it a model or an xray structure?
If it is an ion channel, how did you treat ionizable residues in the
channel? Did you perform a pka calculation on the protein prior to
simulation to set ionization states?
How much lipid slab is there versus the size of the protein?
Has your lipid density converged? Are you using constantarea? What setting's
are you using during the equilibration? Do you want to post your input

In the end there may not be a good solution to your problem but depending on
the computer time you have available you could test different settings. The
FF for membranes in NAMD is clearly not perfect.


p.s. there are plenty of people on this list just as well, if not more
qualified than me to answer your questions on this, but having said that,
membrane protein simulations are still are still in their infancy and I know
a lot of groups are trying to improve protocols and forcefields to make the
membrane behave better over longer simulations.

On 10/12/07, Ilya Chorny <> wrote:
> Dear Richard,
> I got your contact info from the NAMD mailing list. I am a member of the
> Stroud Lab at UC San Francisco and I am working on a membrane protein
> simulation. I am having some trouble with my protein. I prepare my
> simulation box by inserting the protein into the membrane, deleting
> overlapping lipids, solvating the system and adding counter ions. I minimize
> and then equilibrate the system for 2 ns. In the initial 2 ns simulation I
> fix the position of protein atoms and constrain the lipid phosphates in the
> Z dimension (along the pore axis). I then run an 8ns simulation in which I
> release the constraints on the lipid and constrain the CA positions of the
> protein. After my 10 ns equilibration I run another 8 ns simulation in which
> the whole system is free. In the last 8 ns simulation my protein seems to be
> falling apart. The RMSD keeps increasing and the channel residues which
> should be fairly constrained move all over the place. I monitor my
> equilibration by calculating the protein-lipid energy which seems to have
> converged. Any ideas on what I can do to debug my problem? The membrane is
> Thanks,
> Ilya

Dr. Richard J. Law
Biosciences & Biotechnology Division
Chemistry, Materials and Life Sciences Directorate
Lawrence Livermore National Laboratory
L-372, 7000, East Ave,
CA.  94550  USA
tel: +1 925 424 2338
fax: +1 925 424 4334

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