Re: [AMBER] Sampling of membrane-protein system

From: Jason Swails <>
Date: Wed, 11 Nov 2015 08:10:42 -0500

On Wed, Nov 11, 2015 at 6:13 AM, Ofir Tal <> wrote:

> Dear members,
> 1.
> I simulate large system (~250 thousand atoms) of membrane protein dimer
> embedded inside a POPC membrane on 2X gtx980 GPUs.
> The system and its variant ran 200ns. The systems are stable in terms of
> energy and area-pre-lipid. RMSD seems to keep constantly raising along the
> simulation, although less in comparison with the first 50ns. RMSD increased
> by ~1A during the last 150ns.
> I want to enhance the systems sampling sufficiently, so I think it need to
> be sampled in one of the methods - aMD or umbrella.
> Which of the methods would be the best choice for sampling a big membrane
> system?

​They are completely different and used for completely different purposes.
Umbrella sampling gives you a PMF -- which is effectively a free energy
along a *particular* degree of freedom (or multiple degrees, if you do
multi-dimensional umbrella sampling). To do this, you need to know, in
advance, what degree of freedom you want to enhance sampling along.

aMD is used when you *don't* have a particular degree of freedom you want
to enhance sampling for.​ It simply boosts the sampling of many degrees of
freedom "blindly".

These two methods are rarely (if ever) relevant to the exact same problem
(so the choice as to which is "better" for a particular application is
almost always obvious).

Is it possible or sufficient to run the simulations in triplicates with
> different random seeds (200ns each) instead?

"Sufficient" is hard to define, and depends on what you're trying to
learn. This is sufficient for *some* things, but not others I am sure.

> As I understand from the literature, in general is not suitable
> for membrane systems. Is it possible to calculate binding energy values (of
> the membrane complex) using just the 'Decomposition' method of MMPBSA,
> directed to the interaction area of the two sub-units (only between
> residues which participate the interaction of sub-unit-A and sub-unit-B)?

​I wouldn't do that. You can run an end-state free energy type of analysis
"by hand" using PBSA, since it supports membrane calculations (but in this
case, the membrane is implicit, not explicit). But will not
realistically be able to handle this system.


Jason M. Swails
Rutgers University
Postdoctoral Researcher
AMBER mailing list
Received on Wed Nov 11 2015 - 05:30:04 PST
Custom Search