[gmx-users] parameter for repeating units with cgenff

[Justin Lemkul]

On 12/11/15 2:20 PM, gromacs query wrote:
> Hi Justin
>
> Thanks for the explanation. Just few things.
>
> 1) When you say " Initial charge fitting would be done on a side chain ..."
> you mean using some QM method? Which seems expensive and needs expertise
> which I dont have.
>

Yes, these are generally the initial target data (gas-phase dipole moment, water 
interactions, etc).  Most of these calculations are done by optimizing the 
structure at MP2/6-31G*, which is very straightforward in, e.g. Gaussian.  The 
CGenFF paper has all the details; this is, in essence, what is done for the 
biomolecular CHARMM force field, as well.

> 2) Also, as you said assigning charges and types with analogy does this
> mean I can hand pick types and charges looking (carefully) some residues
> available with CHARMM and can directly use them? At the same time, then in
> this case, I should satisfy the condition of overall integral charge. Am
> just wondering in future if reviewer raises question :)
>

This is what is generally done.  In fact, this is largely what CGenFF is doing, 
too.  Initial selection of parameters based on rules that reference the library 
of existing compounds.  Refinements are then done based on the initial topology.

-Justin

>
> On Fri, Dec 11, 2015 at 6:33 PM, Justin Lemkul <jalemkul at vt.edu> wrote:
>
>>
>>
>> On 12/11/15 1:28 PM, gromacs query wrote:
>>
>>> Hi Justin
>>>
>>> I am bit lost I think. For e.g. in the amino acid residues library we have
>>> -CO-CH(R)-NH- which we can combine these amino acids in any way and in the
>>> rtp file it defines only these atoms and connecting atoms are mentioned
>>> specifically.
>>>
>>> Now lets say I have some new amino acid -CO-CH(X)-NH- which I want to
>>> combine with some existing amino acids. If I want to derive charges from
>>> Cgenff what kind of residue I should prepare?
>>> Is it NH2-CO-CH(X)-NH-COOH or may be CH3-NH-CO-CH(X)-NH-COCH3. But
>>> ultimately I will be requiring only -CO-CH(X)-NH- part. So not considering
>>> charges for the caps in topology will give non-integral charge or in other
>>> words this part -CO-CH(X)-NH- will always be non-integral. Sorry am
>>> confused.
>>>
>>>
>> The backbone group always has a charge of zero, so you only deal with the
>> side chain when deriving charges.
>>
>> Initial charge fitting would be done on a side chain analog that
>> terminates in a -CH3 that is analogous to CB.  Once that work is done, the
>> model compound is merged with the backbone and CB (which is -CH2, so
>> generally the third H charge is just lumped into the C charge) and
>> torsional fitting is done for chi1/chi2/etc using a dipeptide model of the
>> amino acid.  But at that point the charges are done.
>>
>> I also wouldn't use CGenFF for a modified amino acid; derive parameters by
>> analogy from the parent CHARMM force field.  CGenFF is generalized, at the
>> expense of some accuracy.  Mixing CGenFF into a polypeptide chain is not
>> the most robust approach.  CHARMM has excellent coverage for most chemical
>> moieties.  Simply assigning charges and types by analogy should be quite
>> straightforward.
>>
>>
>> -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

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