[gmx-users] Re: Bilayer

[Justin A. Lemkul]

Please keep all Gromacs-related correspondence on the gmx-users list.  I cannot 
serve as a private tutor, and I do get numerous requests.  You stand a much 
better chance of reaching someone with useful advice by posting to the list.  I 
have a few ideas (see below), so I am CC'ing the list to benefit the community 
and perhaps stimulate further responses.  Archiving your questions and responses 
will help others down the road who have the same issues.  That also reduces my 
personal inbox traffic :)

Clark, Tiffany D wrote:
> Hello Mr. Lemkul,
> 
>  
> 
> I am a graduate student at East Carolina University and I am trying to 
> construct a heterogeneous lipid bilayer for use in a md simulation using 
> GROMACS.  As I have been searching for help online you have emerged as 
> an expert in the field with your ablity to provide the most insight and 
> helpful advice.  I am hoping you are willing to share some of your 
> knowledge with me.
> 
>  
> 
> I am trying to create a 4:1 mixture of POPC and POPG respectively.  I 
> will be using the Berger lipids force field (lipid parameters by D. 
> Peter Tieleman).  I am thinking the best approach maybe to construct a 
> set of  lipids (DPOPC, LPOPC, DPOPG and LPOPG) and then propagate that 

There is no need to re-construct any lipids.  Just extract a single lipid 
molecule from the pre-equilibrated bilayers at Tieleman's site.  Don't 
differentiate between different stereoisomers of POPC; the topology provided by 
Tieleman does not pertain to both possible forms.

> using GROMACS editconf.  I am struggling with how to get things 

A combination of editconf and genconf would be useful.  You could construct a 
small box with the appropriate lipid ratio, then replicate it with genbox -nbox 
to create a monolayer of sufficient size.  Create a duplicate monolayer and 
rotate it with editconf, concatenate the structures, and presto, you have a 
bilayer.  This structure will of course require substantial equilibration (tens 
to hundreds of ns) due to its artificial regularity.

> started.  I  have .itp files for both POPC and POPG (from 
> http://moose.bio.ucalgary.ca/index.php?page=Downloads) but how do I 
> generate topologies for the new positions of the lipids?  I have noticed 

Topologies and positions are independent.  The only requirement is that the 
[molecules] section of your .top matches the order of the molecules present in 
your coordinate file (aside from the obvious nomenclature of atoms).

> that may people have just changed the head group and made small changes 
> to the topology file
> 
>  
> 
> Is the only way to create a GROMACS .top file for a lipid to write it 
> yourself?  What is the best way to generated the starting coordinates of 

It should be very straightforward to write the topology, just #include the 
necessary topologies (all of which you already have) within the .top file.

> my lipids?  I have constructed each of the lipids and minimized the 
> structures (using Amber), though I don’t think this will be useful for 
> the construction of the bilayer (in GROMACS).  The .pdb files available 

Probably not.  The AMBER-output structures will likely be all-atom molecules 
with atom naming that has no relationship to the names defined in the 
Tieleman-provided topologies.  See my comment above for a reasonable (and 
extraordinarily easy) method for getting the coordinates of a single lipid.

> on Dr. Tieleman’s website are bilayers and not individual lipids (would 
> you advise me to start with a lipid structure isolated from one of the 
> bilayers?). 
> 

Indeed, yes :)

>  
> 
> Any advice or recommendations you are willing to share would be most 
> appreciated.  None of the faculty here work with GROMACS and I am 
> struggling to understand how a bilayer can be constructed based upon 
> topology files (.itp) or if only amendments are possible.
> 

Then you've been assigned an unfortunate task.  What you are looking to do is 
fairly complicated for someone who is unfamiliar with GROMACS and without an 
immediate support system you are in for a lot of archive reading and waiting 
around for free help.

What you really need to get comfortable with is the fact that a topology has 
nothing to do with coordinates, thus no structure can be built from a topology. 
  Crafty use of editconf and genconf are all you need to build the system.

Good luck.

-Justin

>  
> 
> Gratefully yours,
> 
>  
> 
> Tiffany D. Clark
> 

-- 
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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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