[gmx-users] Manual refinement of ATB topologies ?

Sim gmx simgmx at gmail.com
Mon Dec 19 15:43:27 CET 2016

Again, thanks a lot for taking the time to reply me.

So you think I should submit this model compound to ATB as a "starting
block" for my molecule ?
Actually my whole molecule looks like this:

(ring system)-(C=O)-CH=CH-CH=CH-CH2-CH2-CH2-CH2-CH3

So there is this annoying second double bond that (I guess) I am obliged to
include into the model I would submit to ATB. Thus I have the feeling that
the shortest molecule that I could use as a model compound would be:

(ring system)-(C=O)-CH=CH-CH=CH-CH3

which is my whole molecule minus butane. So, couldn't I use the
ATB-topology of my whole molecule (that I already have) and change these
last methyl groups that should not carry any charge ?

Nice to read your considerations about Berger and gromos FF, I easily hung
up on those things... (if/when you have some time, you can get a
confirmation here

OK, it sounds great indeed, I should definitely have a look at this FF. Is
it possible to quickly get started with CHARMM ? Possible to launch the
first simulations in one week or so ? Also, I get a warning message when
trying to connect to CGenFF ("unsafe connexion"), should I ignore this ?

Thank you, have a nice day !

2016-12-19 14:13 GMT+01:00 Justin Lemkul <jalemkul at vt.edu>:

> On 12/19/16 7:50 AM, Sim gmx wrote:
>> 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 ?
> This is common to all additive force fields.  You need a suitable model
> compound, one that includes linker portions that can be merged with
> neighboring functional groups by combining charges and applying/modifying
> known dihedrals. What I would do is try to parametrize:
> (ring system)-C=O-CH=CH-CH3
> and whatever might be a suitable flanking group for the ring (e.g. methyl
> or ethyl, etc) if it is in the middle of the acyl chain.  There may be
> partial charges on those neighboring methyl/methylene groups.  That would
> be normal. But putting partial charges on UA carbon atoms multiple bonds
> away is not intuitive, given the philosophy of the force field.  I would
> assume positive-positive repulsion would perturb the bilayer, unless the LJ
> mask the issue.
> 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.
> Berger lipids were derived from old GROMOS parameters and some aspects of
> OPLS, so don't get too hung up on whether or not interactions are
> Berger-Berger or Berger-GROMOS.  They're compatible.
> 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 ?
> I do everything with the CHARMM force field nowadays.  Parametrization is
> straightforward and the CGenFF server parametrizes small molecules and
> model compounds easily, and they can then be converted to GROMACS format
> with a script from the MacKerell group website.  The parametrization theory
> and protocol for CHARMM is published in extensive detail, as much or more
> so than any other force field out there.  The lipid force field reproduces
> many experimental properties well.  For those reasons, I think it is an
> optimal choice in a situation like this.  Of course, that comes at the
> price of more expensive simulations (all-atom with required
> force-switching) but that's a price I find worth it.
> -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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