First, yes, it is possible to divide the molecule into parts and treat
the parts the way you describe. Since you will be doing something a
bit novel, you definitely need to validate the model you generate.
But, yes, you can do that.
> So if I find things not in accordance with experimental data, what can I do
> to change it manually?
That's not a simple question to answer. In part, it depends what you
find that isn't in accordance. Whatever you do, you need to be
careful. The parameters are interrelated, and what counts isn't the
specific value of any one parameter, but the values taken by the
specific bonds, angles, etc., in a minimized or simulated molecule.
That is, if you vary one parameter, say a bond equilibrium value, to
be exactly what you expect it to be, you might find that you've thrown
other values out of whack. Once you fix those, your bond parameter
might be ok, but when placed in a molecule and minimized, you might
never observe the value you wanted.
In relation to that, is also important to note that these force fields
are developed to be somewhat general. That is, any given structure is
likely to behave very similarly to its real counterpart within
contexts appropriate to the force field, but they are still
approximations. In other words, all the values are likely to be a
little bit off. But, in cases where the simulation is reasonable,
the extent to which they disagree should not be large enough to be
important.
There is one other caution in comparing to experiment: compare to the
experimental observation whenever possible, not to the conclusion
drawn by the researcher. For example, assume you find a study where
j-couplings are used to determine certain torsions. The torsions
reported in the study are conclusions the researcher made based on
observed j-couplings. It is better to run a simulation and predict
observed j-couplings from the ensemble-averaged, simulated torsions.
Then, compare the j-couplings you predict to those that are observed.
:-) L
On Fri, Aug 19, 2011 at 12:31 PM, Yun Shi <yunshi09.gmail.com> wrote:
> Hi Lachele,
>
> So if I find things not in accordance with experimental data, what can I do
> to change it manually?
>
> Is it technically possible to do it due diligence in the first place? That
> is, cut the molecule into three parts as I mentioned before, use GLYCAM for
> the sugar part, 99SB for the Thr, and GAFF for modified Phe and the
> thio-glycosidic linkage. And may I then link these parts together using LEaP
> ?
>
> Thanks,
>
> Yun
>
> On Tue, Aug 16, 2011 at 12:39 PM, Lachele Foley (Lists)
> <lf.list.gmail.com>wrote:
>
>> GAFF should get you a reasonable result. You'd definitely need to do
>> some validation to be sure things are working right (check angles or
>> H-bonding or whatever you can find experimental values for). You
>> might ask if it matters. For example, if you are simulating a tightly
>> bound complex, then the glycosidics can't change anyway. If they can
>> change, then you need to find some way to determine whether or not the
>> method is working. It would take significant work to get Glycam
>> working with all parts of this system.
>>
>>
>> On Tue, Aug 16, 2011 at 2:34 PM, Yun Shi <yunshi09.gmail.com> wrote:
>> > Hi all,
>> >
>> > I have a small molecule that consists of a Thr with an ACE cap, a
>> modified
>> > (CO becomes CH2) Phe, and a rhamnose linked to Phe via a thio-glycosidic
>> > linkage. And please see attached the molecule I drew.
>> >
>> > While the Thr and Rha are the standard building blocks of GLYCAM06 and
>> 99SB
>> > force fields respectively, what about the modified Phe and the
>> > thio-glycosidic linkage?
>> >
>> > As what seemed to be discussed before in the archive, GAFF can be applied
>> to
>> > the entire molecule. But the sugar ring is very sensitive to dihedral
>> > parameters, right? So the GAFF parameters (and am1-bcc charges) may not
>> be
>> > good enough for sugar?
>> >
>> > Thus, I wonder if it's possible to add all the bond, angle, dihedral, and
>> > charge parameters for the modified Phe and the thio-glycosidic linkage by
>> a
>> > .frcmod file. But where can I find proper parameters for thio-glycosidic
>> > linkage? Could anyone tell me the steps (formats) to construct such a
>> > .frcmod file?
>> >
>> > Any help is appreciated!
>> >
>> > Thanks,
>> >
>> > Yun Shi
>> >
>> > _______________________________________________
>> > AMBER mailing list
>> > AMBER.ambermd.org
>> > http://lists.ambermd.org/mailman/listinfo/amber
>> >
>> >
>>
>>
>>
>> --
>> :-) Lachele
>> Lachele Foley
>> CCRC/UGA
>> Athens, GA USA
>>
>> _______________________________________________
>> AMBER mailing list
>> AMBER.ambermd.org
>> http://lists.ambermd.org/mailman/listinfo/amber
>>
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
>
--
:-) Lachele
Lachele Foley
CCRC/UGA
Athens, GA USA
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Received on Fri Aug 19 2011 - 11:00:03 PDT
