[gmx-users] Manual refinement of ATB topologies ?

Thu Dec 22 14:40:58 CET 2016

On 12/22/16 8:25 AM, Sim gmx wrote:
> 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.

I just remain skeptical that such a representation is physically valid.  Just 
representing a double bond as an uncharged entity in the middle of an uncharged 
chain, while consistent with the force field's underlying theory, seems quite 
inadequate to me.  If ATB is suggesting an alternate, it should be explored.  I 
think this is polar character that is not accounted for in the simplistic 
uncharged model.  To what extent that affects the dynamics needs to be examined.

> 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) ?

Impropers keep planar groups planar; they do not keep bonds in cis or trans 
orientation.

> 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) ?
>

If it's me doing it, I'd test both topologies.  I've done simulations with, POPC 
and a simple, uncharged model and didn't notice anything out of the ordinary but 
I've grown skeptical.  You have multiple double bonds in your compound, 
separated by only one bond, and their properties may depend on a more precise 
electrostatic representation.

-Justin

>
>>
>> - 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
>>>>>>>
>>>>>>> ==================================================
>>>>>>> --
>>>>>>> Gromacs Users mailing list
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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
>>
>> ==================================================
>> --
>> Gromacs Users mailing list
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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

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