Re: [AMBER] Few queries about membrane protein simulations

From: Ross Walker <>
Date: Mon, 8 Jun 2015 09:17:38 -0700

Hi Anu,

> My queries are,
> 1. I wish to use lipid 14 and FF14SB force fields for membrane and protein
> respectively. Will it be okay? Do I have to use any correction terms here?
> I will be using POPC membrane.

Yes this is fine and no correction terms are needed.

> 2. I have noticed in literature that , for microsecond long simulations,
> sometimes a 3 fs or 4 fs time steps were used. How safe to use such a large
> simulation time step, though it reduce the use of computations resource?

You can use 4fs time steps as long as you enable hydrogen mass repartitioning - see

Hopkins C.W., Le Grand, S., Walker, R.C., Roitberg, A.E., "Long Time Step Molecular Dynamics through Hydrogen Mass Repartitioning", J. Chem. Theory. Comput., 2015, 11 (4), 1864-1874, DOI: 10.1021/ct5010406

Although this has not been extensively tested with membranes.

> 3. The membrane protein, I am working with, transport ions depend on the
> concentration gradient. In order to implement this in my simulation, I am
> planning to add ions ( for e.g KCl) in one of the leaflet to see the
> movement of ions to the other leaflet through the pore. Am I making sense
> here, by restricting ion distribution to only one of the leaflet rather
> than randomly placing in the entire simulation box (usually do for protein
> simulation) at the starting of simulation?

We are working on support for asymmetric boundary conditions that will effectively invert the symmetry in the Z direction allowing for ion gradients. At present though this is not released. Your only real option right now is to build a double bi-layer which will work fine but makes you simulation larger and thus more expensive computationally. If you don't do this then ions can just diffuse out the top of the box and thus appear in the bottom of the adjacent box and therefore mix without having to traverse the membrane.

> 4. How can I build slab geometry boundary condition in Amber to maintain
> ion asymmetry? (

You would need to modify the code to support this. I would take a good look in the literature at the different methods people have tried before determining which is optimal. One thing that concerns me in the paper you reference here is the term:

"It was shown recently that the Ewald method devised for systems with three-dimensional boundary conditions can also be applied to systems with slab geometry if the correct surface term is considered."

Note the use of a 'surface term' - this is something completely artificial and what everyone in the field developing lipid force fields has been working to move away from over the last several years.

> 5. If I would like to do membrane protein simulations with an applied
> electric filed along Z-direction, how can I implement the electric field in
> Amber simulations?

Again you would need to add code to do this but it should not be too difficult and would be less work than changing the way the boundary conditions work. Although you'll need to figure out how to make this behave correctly with PME. If you turn off PME then there is no warranty on the lipid parameters. ;-)

> 6. Is it possible to do PMF calculation with classical MD trajectories or
> do I want to carried out umbrella sampling separately for PMF?

Yes you can do a PMF by using umbrella sampling. For example constraining the center of mass of the bilayer or protein to a molecule of your choice with the restraint just applying in the Z direction. Then just reconstruct things with WHAM.

> 7. Though I wish to use Amber for membrane protein simulation, some one
> kindly provide some reference for membrane protein simulation where Amber
> used? ( sorry, I couldn't get one)

All the best

|\oss Walker

| Associate Research Professor |
| San Diego Supercomputer Center |
| Adjunct Associate Professor |
| Dept. of Chemistry and Biochemistry |
| University of California San Diego |
| NVIDIA Fellow |
| | |
| Tel: +1 858 822 0854 | EMail:- |

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Received on Mon Jun 08 2015 - 09:30:03 PDT
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