Re: [AMBER] parameters for Lys-sugar

From: Lachele Foley (Lists) <"Lachele>
Date: Sun, 25 Mar 2012 16:10:23 -0400

Developing force field parameters is not a trivial task. However, the
amount of effort required can be adjusted somewhat, depending on the
ultimate goal. For us, the goal is to produce a force field that can
be used to generate good models for many different types of
carbohydrate in a wide range of biologically relevant contexts. This
approach is the most general, and in the long run a lot less work
overall. But, it takes a lot of effort up front to do it well.

For more on our methods, see: Kirschner, K.N., Yongye, A.B., et al.
J. Comput. Chem. 2008, 29, pg 622-655

It is also possible to have great success with parameters developed
for a specific molecule in a specific context. If you are not
expecting to need to develop parameters often, this approach might be
useful to you. Just be extra careful in validation. Also note that
parameters made this way are rarely useful outside that context, but
can, if well made, be far more accurate within the context they were
designed for than other, more general, sets would be.

The paper below is a review that contains a lot of information about
many different methods people have used to develop force fields for
carbohydrates over the years, including some developed for very
specific contexts. It also contains many examples of
force-field-based simulations of carbohydrates as well as tips for
validating models and reporting results.

An extensive review article: Foley B. Lachele, Tessier Matthew B.,
Woods Robert J.. Carbohydrate force fields. WIREs Comput Mol Sci 2011.
doi: 10.1002/wcms.89
(online: )

:-) L

On Sat, Mar 24, 2012 at 4:41 PM, Urszula Uciechowska
<> wrote:
> Dear Lachele,
> Thank you for responding.  I would like to have those parameters properly  modelled ... Could you give me some help with that?
> I will try with RED as well what could be good for comparison ...
> best regards
>  Urszula
> ________________________________________
> Von: Lachele Foley (Lists) []
> Gesendet: Freitag, 23. März 2012 20:39
> An: AMBER Mailing List
> Betreff: Re: [AMBER] parameters for Lys-sugar
> 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)
> <> 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 <> wrote:
>>> Urszula,
>>>> Thank you, this is a part of a peptide, attached is the whole
>>>> peptide structure ...
>>> So you might start from a dipeptide:
>>> R.E.D. Server can generate different fragemtnts automatically as well:
>>> 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 <> 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
>>>>> or, you might decide to split your molecules into two parts; a glyco
>>>>> part and a AA part...
>>>>> regards, Francois
>>> _______________________________________________
>>> AMBER mailing list
>> --
>> :-) Lachele
>> Lachele Foley
>> Athens, GA USA
> --
> :-) Lachele
> Lachele Foley
> Athens, GA USA
> _______________________________________________
> AMBER mailing list
> _______________________________________________
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:-) Lachele
Lachele Foley
Athens, GA USA
AMBER mailing list
Received on Sun Mar 25 2012 - 13:30:03 PDT
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