[gmx-users] Manual refinement of ATB topologies ?

[Justin Lemkul]

On 12/16/16 7:46 AM, Sim gmx wrote:
> Hi all,
>
> I would like to know what you consider to be the ideal refinement for a
> topology created by ATB ?
> How far should we go in the manual refinement ?
>
> For instance, ATB gave me a topology for a molecule with an unsaturated
> acyl chain. Here are some potential issues with this topology:
>
> 1) Three methyl groups at the end of the acyl chain (that are "3 methyl
> groups away" from a double bond) carry a small charge (with a net group
> charge of 0, however)
> 2) For the double bonds, parameters are "new parameters" (not found in
> ffbonded.itp file)
> 3) Some bonded parameters in the ATB topology do exist in ffbonded.itp file
> but are not supposed to be applied for this kind of bond (example: O - S
> bond parameters are written for a C (involved in a double bond) - CH2 bond)
>
> My "instinctive" behavior would be to:
>
> 1) Put a 0 charge to these methyl groups since they should not be charged
> imo
> 2) Look for another gromos53a6 topology that includes a double bond (like
> this one https://lipidbook.bioch.ox.ac.uk/package/show/id/16.html) and take
> the double bond parameters from it
> 3) Replace those bonds by correct "default parameters" found in
> ffbonded.itp file, in this case by a "C, CHn - C, CHn" bonded parameter.
>
> However, I don't wish to break an "equilibrium" that ATB could have built
> with some apparently weird parameters.
>
> Hence, is it better to take the ATB topology as it comes, or to try to
> refine it ? If the latter, how far should we go ? Isn't it risky or
> complicated to justify (in a reviewing process, for example :)) ?
>

You shouldn't be trying to parametrize an entire lipid all at once, anyway.  You 
should only be addressing moieties for which parameters do not exist, and the 
combining them with known moieties.  GROMOS96 has fairly comprehensive lipid 
parameters that can be used (though other force fields may be better, and lipids 
are quite hard to get right).

-Justin

-- 
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Justin A. Lemkul, Ph.D.
Ruth L. Kirschstein NRSA Postdoctoral Fellow

Department of Pharmaceutical Sciences
School of Pharmacy
Health Sciences Facility II, Room 629
University of Maryland, Baltimore
20 Penn St.
Baltimore, MD 21201

jalemkul at outerbanks.umaryland.edu | (410) 706-7441
http://mackerell.umaryland.edu/~jalemkul

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