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

[Justin Lemkul]

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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