[gmx-users] Manual refinement of ATB topologies ?

Thu Dec 22 14:25:13 CET 2016

Hello,

2016-12-22 13:56 GMT+01:00 Justin Lemkul <jalemkul at vt.edu>:

>
>
> On 12/22/16 4:28 AM, Sim gmx wrote:
>
>> Hello,
>>
>> Thank you very much for your help!
>> Good reference indeed! Just to be sure:
>> - ATB gave me HC and C atom types instead of 'CR1' for the CH groups
>> involved in double bonds. Would it be right to merge the two atomtypes
>> (i.e. deleting the HC atoms and changing C atoms to CR1) and add up their
>> respective charges to get the charge of each CR1 atoms ?
>>
>
> Why do this?  Few GROMOS species even use CR1 any more, as it appears to
> be a backwards compatibility with old GROMOS parameter sets that used a UA
> aromatic type.  Phe, Tyr, etc. use C-HC as these are somewhat "polar" C-H
> bonds so the H is represented explicitly.  I'd leave the parameters alone,
> mostly because you need the H and associated parameters there to determine
> the geometry of the double bond.
>

Because in the itp files from the suggested paper above (Poger et al.) they
used CR1 atomtypes for the CH groups involved in double bonds. I would be a
bit afraid if I had to justify in a reviewing process why I took their
parameters for the double bond but did not use the same atom typing, I
might be a bit paranoid though.
If I define an improper dihedral with a torsion angle of 180°, wouldn't it
be a trans double bond anyway (no matter the presence or absence of the H
atoms) ?
Do you think I should leave the HC atoms alone and include 2 improper
dihedrals for each double bond ? One for H-C=C-C and the other one for
C-C=C-H (both with a torsion angle of 0, resulting in a trans double bond) ?

>
> - gromos53a6, the FF that I use, does not include gi_4 parameter that seems
>> to be gi_1 with a 180° angle value instead of 0 (for the trans double
>> bond). I guess I can just add this line in my 53a6 ffbonded.itp file or
>> manually include the right parameters in the topology file of my molecule.
>> Basically, there is no need to switch to the whole 54a7 FF in my case ?
>>
>>
> Right.
>
> -Justin
>
> Thanks for your reply !

>
> Have a nice day !
>>
>> 2016-12-21 15:27 GMT+01:00 Piggot T. <T.Piggot at soton.ac.uk>:
>>
>> Hi,
>>>
>>> This paper, and in particular the SI which has parameters for a lipid
>>> tail
>>> with a conjugated double bond, may be of interest here:
>>>
>>> http://pubs.acs.org/doi/pdf/10.1021/acs.jpcb.5b00958
>>>
>>> From a very quick look at the work, they have used the standard double
>>> bond parameters (itps are given in the SI) and claim it works ok (e.g.
>>> though similarities in order parameters to other works). Given these are
>>> the original developers of the GROMOS54A7 lipids, I would suggest that
>>> this
>>> is therefore probably a reasonable thing to also do for this bit of your
>>> molecule.
>>>
>>> Cheers
>>>
>>> Tom
>>>
>>> ________________________________________
>>> From: gromacs.org_gmx-users-bounces at maillist.sys.kth.se [
>>> gromacs.org_gmx-users-bounces at maillist.sys.kth.se] on behalf of Sim gmx
>>> [
>>> simgmx at gmail.com]
>>> Sent: 21 December 2016 09:49
>>> To: gmx-users at gromacs.org
>>> Subject: Re: [gmx-users] Manual refinement of ATB topologies ?
>>>
>>> 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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> --
> ==================================================
>
> 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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