[gmx-users] Manual refinement of ATB topologies ?

Wed Dec 21 03:16:55 CET 2016

On 12/19/16 9:43 AM, Sim gmx wrote:
> 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 ?
>
I would do two things:

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

and then

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

This will tell you how you might have to reapportion some of the charges, as the 
neighboring CH2 might correctly be assigned some small charge and having it as a 
terminal atom may not be wise.  The terminal CH3 in the model is the (n-3) 
carbon; each of these last three should have zero charge, so you can adjust the 
charges as needed if anything is assigned from the model.

> 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
> https://mailman-1.sys.kth.se/pipermail/gromacs.org_gmx-users/2016-December/109831.html
> )
>
>
> 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 ?
>

To the CGenFF website?  There should be no security issues; maybe the 
certificate is out of date.

-Justin

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

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

==================================================