[gmx-users] Manual refinement of ATB topologies ?

Justin Lemkul jalemkul at vt.edu
Fri Dec 23 19:25:30 CET 2016

On 12/23/16 3:20 AM, Sim gmx wrote:
> 2016-12-22 14:40 GMT+01:00 Justin Lemkul <jalemkul at vt.edu>:
>> 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.
> I see your point. Indeed it looks a bit strange, especially when comparing
> with aromatic structures from amino acids. However, such uncharged double
> bonds are also seen in the widely used lipid parameters from Peter Tieleman
> for Berger Lipids (even though the forcefields are different, I guess this
> comparison is acceptable). It does not mean that it is perfect, but
> hopefully that it is usable.
>> 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.
> OK. But then I don't get the point of creating a gi_4 in gromos54a7 that is:
> #define gi_4         180.0   167.42309
> ; planar groups 40
> while there is already a gi_1 that is
> #define gi_1           0.0   167.42309
> ; planar groups 40
> Am I wrong if I write that the only difference is the ideal angle that
> shifts from 0 to 180° ?
> The use of gi_1 or gi_4 is the only difference I've noticed from the itp
> files of Poger et al. cited above between their trans and cis double bonds.

The convention of impropers depends on how the atom order is given.  Both are 
saying "keep the central atom planar" but perhaps the other atoms are listed in 
a different order.

>> 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
> To be sure that we are talking about the same thing, "both topologies"
> means the double bond parameters as they exactly come from ATB server *and*
> the double bond parameters modified according to Poger et al., right ?


> How would you do then to select the "best one" ? Except if they exhibit
> totally different behavior (which is unlikely, I guess), it seems quite
> complicated to establish. Still I will give it a try! It is true that this
> proximity between the two double bonds could have a marked effect on
> electrostatics.

Understanding whether or not your force field/topology is right requires target 
data.  If you don't have target data, you can't know if your model is right.  If 
you can't know that, you can't know if your results have any physical meaning. 
This is one of the problems with GROMOS parametrization; it's highly empirical 
which means it can be hard to acquire reference data.  Other force fields like 
AMBER, CHARMM, and OPLS have clear connections with QM data that make for easy 
initial checks for dipole moments, water interactions, conformational energy 
scans, etc.  ATB does some QM-based optimization, but unless you know what 
you're explicitly targeting, it only does you so much good.



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


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