Thanks a lot Lachele.
I do have other thio-glycosidic compounds with J-coupling data that I want
to do MD simulation with.
But before trying the dividing methods I propose, I am still wondering what
are the techniques to modify parameters such as an ideal bond lengths and a
dihedral force constant. Should I do this through a .frcmod file? Because I
found the .prmtop so difficult to interpret, not to mention to modify.
Regards,
Yun
On Fri, Aug 19, 2011 at 10:39 AM, Lachele Foley (Lists)
<lf.list.gmail.com>wrote:
> 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
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> >> >
> >> >
> >>
> >>
> >>
> >> --
> >> :-) Lachele
> >> Lachele Foley
> >> CCRC/UGA
> >> Athens, GA USA
> >>
> >> _______________________________________________
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> >>
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> >
>
>
>
> --
> :-) Lachele
> Lachele Foley
> CCRC/UGA
> Athens, GA USA
>
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Received on Fri Aug 19 2011 - 12:00:03 PDT
