We use QM results from small-molecule models to derive the ff params,
including dihedrals, so the charge development happens afterwards for
us. We need the params first so we can get a good ensemble of
charges. The charges need to be averaged many different states of the
molecule.
The reason GLYCAM uses non-bonded interactions of 1.0 and 1.0 is
because it was impossible to get some sugar-relevant geometries right
using the AMBER standard scalings. I'm just saying that sugars can be
hard to get right, particularly around the anomeric center. Be
careful and validate well. Lately, we like to run at least 50 ns, and
preferably much more, of MD, and then compare the results to
experimental J-couplings or similar. If that isn't enough for good
sampling, we go to REMD or some such. Then, we start trying to do
science.
On Sat, Mar 24, 2012 at 4:14 AM, FyD <fyd.q4md-forcefieldtools.org> wrote:
> Dear Lachele,
>
> I think dihedral force field development is performed _after_ charge
> derivation.
>
> In this case, one should (i) derive the charges and build the FF
> library(ies) for the new molecular fragment(s), define the FF atom
> types etc... (and may-be for models as well), and then (ii) perform MD
> simulation to match experimental/QM data, and/or fit MM to a QM
> profile. Indeed, non-bonded interactions are used during the dihedral
> profile fit...
>
> regards, Francois
>
>
>> There is agreement in the group that the linkage position could be
>> hard to model well. Of course, this depends on how well you need it
>> modeled, but for the things we would normally do, we would take some
>> time developing and validating, especially for something like this.
>>
>>
>> On Fri, Mar 23, 2012 at 2:01 PM, Lachele Foley (Lists)
>> <lf.list.gmail.com> wrote:
>>> My concern isn't so much developing the charges so much as is finding
>>> good parameters for the rest of the force field in the linkage
>>> environment. The anomeric center is complex to model all by itself.
>>> If you add a positively charged group so close by, that's likely to
>>> complicate things more.
>>>
>>> For the charges, especially with the tight and complex charge
>>> distribution you have there, I recommend an ensemble average. If you
>>> just use a few structures you might end up with charges that bias the
>>> structure in some manner. I think RED can be used for an ensemble of
>>> structures. Francois can help more with that. We do all ours
>>> in-house, of course. But, the results should be equivalent.
>>>
>>> Definitely validate whatever you decide to use. Find experimental
>>> j-couplings or something else that you can calculate from the
>>> structure. This is especially important in your situation. If you
>>> can't find any experimental values, then validate against appropriate
>>> quantum structures.
>>>
>>>
>>> On Fri, Mar 23, 2012 at 12:11 PM, FyD <fyd.q4md-forcefieldtools.org> wrote:
>>>> Urszula,
>>>>
>>>>> Thank you, this is a part of a peptide, attached is the whole
>>>>> peptide structure ...
>>>>
>>>> So you might start from a dipeptide:
>>>> http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php#15
>>>>
>>>> R.E.D. Server can generate different fragemtnts automatically as well:
>>>> http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php#25
>>>>
>>>> regards, Francois
>>>>
>>>>
>>>>> It's not really even a complete lysine, and the attachment is a bit
>>>>> unusual. The proximity of the ring oxygen, the anomeric oxygen and
>>>>> the nitrogen -- all just one carbon removed from each other -- might
>>>>> make good parameterization tricky. I'll think about it a while and
>>>>> ask around in the group. I'll get back to you.
>>>>>
>>>>>
>>>>> On Fri, Mar 23, 2012 at 11:06 AM, FyD
>>>>> <fyd.q4md-forcefieldtools.org> wrote:
>>>>>> Dear Urszula,
>>>>>>
>>>>>>> I have a peptide with a sugar bound (beta-D-Glucose), and I would
>>>>>>> like to run MD on that with a protein later. I am trying to find a
>>>>>>> easy way to
>>>>>>> generate the parameters for this part. I know that I could use a
>>>>>>> RESP-A1A charge model for the entire new residue and scaling factors
>>>>>>> for 1-4 interactions.
>>>>>>> However I have no idea how to start with that ...
>>>>>>> I was wondering if there is any tutorial for that?
>>>>>>> Could anyone suggest me something? I attached a mol2 file of the
>>>>>>> residue with sugar bound.
>>>>>>
>>>>>> Does this Lys-Glc belongs to a peptide? if yes, this likely means you
>>>>>> need a central fragment for this modified amino-acid. You might decide
>>>>>> to start from a dipeptide; i.e. ACE-AA*-NME; AA* is your modified
>>>>>> amin-acid; i.e. Lys-beta-D-Glucose.
>>>>>>
>>>>>> See http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php#15
>>>>>>
>>>>>> or, you might decide to split your molecules into two parts; a glyco
>>>>>> part and a AA part...
>>>>>>
>>>>>> regards, Francois
>
>
>
>
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--
:-) Lachele
Lachele Foley
CCRC/UGA
Athens, GA USA
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Received on Sat Mar 24 2012 - 08:30:02 PDT
