[gmx-users] Manual refinement of ATB topologies ?

Wed Dec 21 10:49:36 CET 2016

Thank you for your reply.

I will try this and, at the same time, try to get started with CHARMM36.

About the bonded parameters, I guess I have to keep for instance the ATB
parameters for the peculiar cyclic structure, but what about let's say the
two double bonds ? I found the 53a6 topology of POPC from lipidbook, which
includes a double bond. The bond and angle types should be the same, but I
would expect a difference for dihedrals since in my case there are two
double bonds in a row.

Yes, to the CGenFF website. OK, I will not care too much so.

2016-12-21 3:16 GMT+01:00 Justin Lemkul <jalemkul at vt.edu>:

>
>
> 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
>
> ==================================================
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