[gmx-users] Manual refinement of ATB topologies ?

Sim gmx simgmx at gmail.com
Mon Dec 19 13:50:30 CET 2016

Thank you for your answer.

"Unfortunately", this molecule has a peculiar structure with a 5-atoms
cycle (including a nitrogen atom) directly bound to a C=O itself bound to a
CH involved in a double bound. I guess that this nearness between the
groups should lead to some "hardly predictable" charge distribution within
the molecule. Hence, if I submit for instance only the 5-atoms cyclic part
to ATB and take the C=O parameters from an existing topology, I guess I
will have a hard time to merge the two parts, am I wrong ?

If I don't get you wrong, my 'instinctive behavior' shares some
similarities with what you suggest (replacing, wherever it is possible, ATB
parameters by 'known parameters'). But if I don't  submit the whole
molecule to ATB, then I don't know how to get "reliable" atomic charges ?

You underline another important thing to consider: the choice of the right
forcefield. Until now I've been working with berger lipids as forcefield
for my bilayers (initially following one of your tutorials, by the way
thanks a lot for this very helpful work !) in combination with small
gromos53a6 molecules. Here, since my molecule includes a large acyl chain,
it could be non ideal to use gromos53a6 parameters while the lipids with
which it should interact are parametrized with berger lipids. Maybe berger
- berger non-bonded interactions would be better for these mainly
hydrophobic interactions ? Nevertheless I don't see how I could create a
berger topology for such a peculiar molecule, especially because I don't
know any ATB-like for this FF.
Maybe another force field could be used for both the bilayer and my
molecule (with the help of a reliable ATB-like website) ? Or would it be
better to use gromos53a6 lipids instead of berger lipids ?

Thank you in advance !

2016-12-16 22:58 GMT+01:00 Justin Lemkul <jalemkul at vt.edu>:

> 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
> --
> ==================================================
> 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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