[gmx-users] molecule parameterization in charmm36 using GAAMP server

Thu Nov 17 18:36:41 CET 2016

Thanks David and Justin for your comments.

David: since I am interested in lipid lipid interactions, and lipids are
well-parametrized in charmm36, I decided to not parametrize whole lipid in
CGenFF.
As I understood and Justin pointer out, CGenFF is good for small molecules
(drug-like) which there is a few of them in the system not a lipid system.

Justin: make sense. I thought so, but, here is what I did and what I was
interested in:

I have a new lipid which the head group is a bit strange (it has a
dioxolane ring in it) and I could not find any similar part in charmm36 by
analogy.
I could get the parameters for the rest of molecule from charmm36 by
analogy, though. Even for smaller pieces of head group.

To get an initial idea about this ring, I used CGenFF and got some
parameters for the ring part and dihedrals involved this ring. I used the
charges from Swissparam as the first approximation for the whole lipid.
Fortunately, CGenFF gave me ~ good parameters for some dihedrals, but not
good enough for two of them (based on Penalty values of higher than 50).
Thus, I picked some parameters (some atom types and dihedrals) from CGenFF
output files. I could pick because CGenFF will find these parameters based
on analogy, in a similar way to how I found the parameters for the rest of
lipid. Besides, there are parameters for bonded and non-bonded interactions
between CGenFF and Charmm36 atom types.
So, I think till here is fine (consistent) and makes sense. Do you agree?

Doing simulations, I found that charges and two dihedrals (the ones with
high penalties from CGenFF) cause problems. So, I decided to do QM
calculations on 1) charges, and 2) only two dihedrals not all of them.
GAAMP seems to be a good option for this. Although I wanted only two
dihedrals, but for calculating charges, I think it is logical to submit the
whole head-group to GAAMP. Doing this, GAAMP gave me parameters for the
desired parameters with some modifications on parameters I got from analogy
(either by myself or suggested by CGenFF).

This is why I rather to keep parameters I found by analogy and just pick
the parameters for charges and two dihedrals.

Regarding all of these, do you think it is better to take all the
parameters from GAAMP server? (GAAMP seemingly has also suggested new
parameters for TIP3P which I think better to stick to the original water
model, the one charmm36 was built on ).

Any suggestion is highly appreciated in advance.

Cheers
Mohsen.

On Thu, Nov 17, 2016 at 6:05 AM, Justin Lemkul <jalemkul at vt.edu> wrote:

>
>
> On 11/17/16 12:56 AM, David van der Spoel wrote:
>
>> On 17/11/16 01:24, Mohsen Ramezanpour wrote:
>>
>>> Dear Gromacs users,
>>>
>>> I used GAAMP server to get the parameters for a small molecule (this is
>>> part of a larger molecule).
>>> This server optimizes the charges and all the soft dihedrals in an
>>> iteration way (consistent with charmm36 and CGenFF philosophy). The
>>> output
>>> files also include modified angle, bond, and all soft dihedral
>>> parameters.
>>> This means, all the parameters are dependent to each other and I have to
>>> use all of them together in my molecule. However, I am not sure about
>>> this
>>> claim.
>>>
>>> My question is then, weather or not it would be OK to ONLY pick the
>>> parameters for "charges" and "ONE of those dihedrals" NOT the suggested
>>> optimized parameters for atom types, angles, bonds, and other soft
>>> dihedrals.
>>>
>>> This is because, when I made the initial .itp file for my molecule, I
>>> could
>>> find bond, angles and soft dihedral parameters by analogy to existent
>>> molecules in charmm36 ff. So, I want to trust on those analogy-based
>>> parameters for now. The only parameters I was in doubt about were
>>> "charges"
>>> and "one of those dihedrals".
>>>
>>> Please let me know your opinion. Thanks in advance
>>>
>> Why not use the official server
>> https://cgenff.paramchem.org/
>>
>
> For a standalone molecule, this is indeed the easier option.
>
> There is a distinction between GAAMP and the CGenFF server that may be
> worth mentioning.  GAAMP completely parametrizes a molecule, therefore
> assuming that no parameters for any of that molecule actually exist, so it
> starts with doing QM, deriving charges, fitting torsions, etc.  It does all
> the work that we do manually (or semi-automatically) when building a force
> field.  This is a good approach if you have something really wild that
> CGenFF won't be able to handle, because CGenFF assigns parameters based on
> analogy, applying a best fit for anything that it doesn't explicitly
> cover.  So each has its place, but even the output topology from GAAMP
> isn't necessarily a "final" topology as additional refinement may be
> necessary.
>
> To the OP's question, no, you can't just pick and choose pieces of the
> topology that you want to use and call it done.  Force fields are
> self-consistent entities, and things like charges, atom types, and
> dihedrals (which really are just correction factors for 1-4 interactions
> due to the failure of nonbonded forms to universally treat inter- and
> intra-molecular interactions) are all interrelated.  You can't necessarily
> just take what you like and leave the rest, especially with dihedrals,
> which are poorly transferable when making changes to the 1-4 atoms.  The
> dihedrals depend on the bonds and angles, because those affect the internal
> geometry, which affects 1-4 distances, which affects the strength of the
> interaction between those atoms, which in turn determines the strength/form
> of the dihedral necessary for that torsion.
>
> -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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