Hi Matthew,
I saw "The initial partial charges for the solute were computed from the
crystal geometry" from the paper you referred. So I guess in order to obtain
initial charges, I should start with either a crystal structure, if
possible, or a QM optimized structure (at the HF 6-31G ** level?). Then use
the HF 6-31G* and CHELPG, with a constraint of 0.01, to derive initial
charges, which can be done automatically on R.E.D. server. And then do MD as
specified in glycam06 paper, and then derive ensemble-averaged RESP charges
... This really seems to a daunting task even with only one small molecule.
So if what is calculated from the newly-built force field is quite different
from experiment, we generally still keep the charges and only modify the
angle and dihedral parameters with some kind of chemical intuition?
Thanks for your explanation.
Yun
On Mon, Sep 19, 2011 at 7:41 AM, Matthew Tessier
<matthew.tessier.gmail.com>wrote:
> Yun,
>
> >> But which MM force field should I use for this MD simulation?
>
> I'm not sure what you're asking here because you're using the GLYCAM force
> field to generate the ensemble averaged charges. The initial charges you
> should use will come from a QM optimized model of a methyl-reducing
> monosaccharide with the thiol-linkage. See:
> M. Basma, S. Sundara, D. Calgan, T. Varnali, R.J. Woods. 2001. Solvated
> ensemble averaging in the calculation of partial atomic charges. J. Comput.
> Chem. 22: 1125-1137.
>
> >> With a lack of experimental data, does that make sense to compare the
> >> minimized structure of the test molecule in solvent with the force field
> >> parameters we are developing, with the QM optimized structure in vacuum?
>
> I think you're asking if comparing the QM properties to the solution MD is
> a
> good comparison. The answer is no. GLYCAM is parameterized to reproduce
> solution properties which is one reason we use ensemble averaged charges.
> Additionally, the glycosidic rotation profiles can be different in
> solution.
> If no experimental data is available for your system then you should find a
> similar thiol-linked model that has experimental data (J-couplings, NOEs,
> etc) to validate against.
>
> -----Original Message-----
> From: Yun Shi [mailto:yunshi09.gmail.com]
> Sent: Friday, September 16, 2011 12:46 PM
> To: AMBER Mailing List
> Subject: Re: [AMBER] about Glycam_06g.dat and thiol-glycosidic linkage
>
> Hi Matthew,
>
> I understand that a MD run is required to generate conformational ensembles
> so that we could calculate ensemble-averaged RESP charges. But which MM
> force field should I use for this MD simulation?
>
> With a lack of experimental data, does that make sense to compare the
> minimized structure of the test molecule in solvent with the force field
> parameters we are developing, with the QM optimized structure in vacuum?
>
> Thanks,
> Yun
>
>
> On Thu, Sep 15, 2011 at 11:53 AM, Matthew Tessier <
> matthew.tessier.gmail.com
> > wrote:
>
> > Yun,
> > I developed part of the thiol-linkage parameter sets and a former
> graduate
> > student developed the initial parameter sets. We had planned to use them
> > on
> > some synthetic glycans but that project didn't get funding. The
> > thiol-linkage parameters should be carefully employed and stringently
> > validated against experimental data since they were only developed on QM
> > models.
> >
> > I don't plan on developing new prep files for thiol-linkage glycans
> > however,
> > there is no reason you can't take the existing prep files and replace the
> > linkage atom type "OS" and replace that with "SM". The only thing you'll
> > have to do is re-develop charges which can be done with the RED server if
> > you'd like. Be sure to generate Ensemble Averaged charges for each
> residue
> > that you use.
> >
> > Please let me know if you have any additional questions.
> >
> >
> > Matthew B. Tessier
> > Complex Carbohydrate Research Center
> > University of Georgia
> > +1 (706) 542-3508
> > mbt3911.uga.edu
> > matthew.tessier.gmail.com
> >
> >
> >
> > -----Original Message-----
> > From: Lachele Foley (Lists) [mailto:lf.list.gmail.com]
> > Sent: Thursday, September 15, 2011 2:40 PM
> > To: AMBER Mailing List
> > Subject: Re: [AMBER] about Glycam_06g.dat and thiol-glycosidic linkage
> >
> > We'll take a look at the paper.
> >
> > I can't make any promises about the prep file, but I'll see if anyone
> > has something in an advanced stage.
> >
> >
> > On Thu, Sep 15, 2011 at 2:07 PM, Yun Shi <yunshi09.gmail.com> wrote:
> > > Hi Lachele,
> > >
> > > Here is the link I used:
> > >
> > > http://pubs.rsc.org/en/content/articlelanding/2011/cp/c1cp20854c
> > >
> > > Should I expect a new version of prep file to include thiol glycosidic
> > > linkage in a few weeks? If not, I will try to do it myself.
> > >
> > > Thanks again.
> > > Yun
> > >
> > > On Thu, Sep 15, 2011 at 10:41 AM, Lachele Foley (Lists)
> > > <lf.list.gmail.com>wrote:
> > >
> > >> 1. Web of Science does not report finding an article containing the
> > >> words "Molecular dynamics studies of native and substituted
> > >> cyclodextrins in different media" in the title. Can you give a more
> > >> complete reference?
> > >>
> > >> 2-3. At the top of the parameter file, you will find atomic mass
> > >> definitions with useful comments. For example:
> > >>
> > >> N 14.01 sp2 N amide group
> > >> SM 32.06 sulfane carbohydrate linkage
> > >> (-CH2-S-CH2-)
> > >>
> > >> 2. Thiol linkages are still in the development phase. That's why
> > >> information for them occurs only in parameter file releases since the
> > >> GLYCAM06 paper. If you want to use them, you will have to generate
> > >> your own prep file entries. To do this, you need to generate
> > >> ensemble-averaged charges for the species you wish to model. You
> > >> should use the procedure as discussed in the GLYCAM06 paper. You
> > >> might be able to loosely base a prep entry on an existing one, but
> > >> that is best done only by someone with a lot of experience doing this
> > >> sort of modeling.
> > >>
> > >> :-) Lachele
> > >>
> > >>
> > >> On Thu, Sep 15, 2011 at 1:03 PM, Yun Shi <yunshi09.gmail.com> wrote:
> > >> > Hi Lachele,
> > >> >
> > >> > 1. I am confused after reading this paper -- Molecular dynamics
> > studies
> > >> of
> > >> > native and substituted cyclodextrins in different media: 1. Charge
> > >> > derivation and force field performances --, which compared the
> > >> performance
> > >> > of GLYCAM04 and GLYCAM06 on cyclodextrins.
> > >> >
> > >> > 2. I do want to a minimization with the force field and then compare
> > it
> > >> with
> > >> > QM optimized structure. But I have some difficulty in building
> > topology
> > >> > file.
> > >> >
> > >> > Something like:
> > >> > .......
> > >> > SM 1.7210 0.2104 OPLS
> > >> > ......
> > >> > appears to the end of Glycam_06g.dat. Are these vdw parameters for
> > sulfur
> > >> > atom in something like a -CH2-S-CH2- environment?
> > >> >
> > >> > No residue as "SME" is defined in prep file, so I have to construct
> a
> > >> > monosaccharide like { OME 0hA } first, and then change the O atom in
> > OME
> > >> to
> > >> > S, and SM atom type?
> > >> >
> > >> > Then what atomic charges should be assigned to the CG and SM atoms
> in
> > >> 'SME'?
> > >> > Should the anomeric carbon CG have a different atomic charge as
> well?
> > >> >
> > >> > 3. For the N -CG-CG-SM sequence, the N should correspond to an amide
> > >> > nitrogen attached to C2?
> > >> >
> > >> > Thanks for the reply.
> > >> > Yun
> > >> >
> > >> >
> > >> > On Thu, Sep 15, 2011 at 8:32 AM, Lachele Foley (Lists) <
> > >> lf.list.gmail.com>wrote:
> > >> >
> > >> >> 1. GLYCAM06 should be used instead of GLYCAM04. The point of
> > >> >> GLYCAM06 is that it does a better job. Like I said in the other
> > >> >> email, if you find any place where 04 is significantly better than
> > 06,
> > >> >> please let us know. It should work well with other good protein
> > force
> > >> >> fields. The basic idea, and there might be times when this is not
> so
> > >> >> valid, is that if you make a really good, general force field for
> > >> >> carbohydrates and a really good, general force field for proteins,
> > >> >> they should, when used in concert, do a pretty good job modeling
> what
> > >> >> proteins and carbohydrates do together.
> > >> >>
> > >> >> 2. Any angle or bond length observed in a molecule is the
> > combination
> > >> >> of many different parameters. For example, if I build and minimize
> > >> >> N-acetyl neuraminate { ROH 0SA }, I find that the bond length
> between
> > >> >> the ring oxygen and the anomeric carbon is 1.44. Their atom types
> > are
> > >> >> OY and CY, respectively. The parameter file, however, gives the
> > >> >> equilibrium bond length for those two types as being 1.410. The
> > >> >> difference is because all the parts of the molecule, all the
> > different
> > >> >> angle, bond and torsion parameters, push and pull on each other.
> > >> >> Certain aspects of any structure, therefore, are expected to
> deviate
> > >> >> from the values found in the parameter file. So, you can't look at
> a
> > >> >> QM bond length or angle from within an entire molecule and expect
> it
> > >> >> to be exactly the same as any individual parameter. Conversely,
> you
> > >> >> cannot, with great precision, predict the bond lengths or angles in
> a
> > >> >> molecule based on individual values in the parameter file. If you
> > >> >> want to know the final values in a molecule, you have to build the
> > >> >> molecule and, at the very least, minimize it using the force field.
> > >> >> All of our parameters are taken from small molecule analogs. This
> is
> > >> >> a design philosophy that seems to work well and is generally not a
> > >> >> cause for concern.
> > >> >>
> > >> >> 3. It is, indeed, a typo. It should be:
> > >> >>
> > >> >> N -CG-CG-SM 1 0.45 0.0 -3.
> SCEE=1.0
> > >> >> SCNB=1.0 Thiol-linkages
> > >> >>
> > >> >> I will get corrected versions up on our site by the end of the day.
> > >> >> Type "N" is defined at the top of the file.
> > >> >>
> > >> >> :-) Lachele
> > >> >>
> > >> >>
> > >> >> On Wed, Sep 14, 2011 at 6:53 PM, Yun Shi <yunshi09.gmail.com>
> wrote:
> > >> >> > Hi there,
> > >> >> >
> > >> >> > 1.
> > >> >> > In the end of this file, it notes that ".....in conjunction with
> > >> Parm94
> > >> >> > without introducing any conflict.....". So what about in
> > combination
> > >> with
> > >> >> > parm99 force field parameter set, would there be any foreseeable
> > >> >> problems?
> > >> >> >
> > >> >> > It seems many people are still using Glycam_04 series parameter
> set
> > >> for
> > >> >> > carbohydrate. I wonder if GLYCAM06 parameter sets are not as good
> > as
> > >> >> > GLYCAM04 in terms of simulating pure carbohydrates?
> > >> >> >
> > >> >> >
> > >> >> > 2.
> > >> >> > In Glycam_06_alldocs.txt, it says that for Glycam_06g.dat,
> "Changes
> > >> >> include
> > >> >> > adding a comprehensive thiol-linkage set for glycosidic linkages
> > >> formed
> > >> >> by a
> > >> >> > Sulfur". So I looked into it, and found some differences between
> > the
> > >> >> ideal
> > >> >> > bond and angle values in the data set and those calculated for a
> > >> sample
> > >> >> > molecule from QM.
> > >> >> >
> > >> >> > I constructed a Met-S-alpha-L-Rhamose molecule, then did three QM
> > >> >> geometry
> > >> >> > optimizations using HF 6-31G*, starting from three different
> > >> >> conformations.
> > >> >> > All three optimized structure showed a CG-SM bond length of about
> > 1.83
> > >> >> > angstrom, while the value is 1.81 angstrom in Glycam_06g.dat. And
> > most
> > >> >> > angles involved in the thiol-glycosidic linkage are off the
> values
> > in
> > >> >> > Glycam_06g.dat by 1 to 10 degrees.
> > >> >> >
> > >> >> > I understand angle parameters for i.e. CG-SM-CG are taken from
> > >> cysteine.
> > >> >> So
> > >> >> > I wonder if it's reasonable to still go head with what are
> > >> Glycam_06g.dat
> > >> >> if
> > >> >> > I am simulating a ligand containing this -S-alpha-L-Rham- part?
> > >> >> >
> > >> >> >
> > >> >> > 3.
> > >> >> > I also found something like:
> > >> >> >
> > >> >> > NH-CG-CG-SM 1 0.45 0.0 -3.
> > SCEE=1.0
> > >> >> > SCNB=1.0 Thiol-linkages
> > >> >> >
> > >> >> > in Glycam_06g.dat. Is this 'NH' a typo? If it is, what kind of
> > >> nitrogen
> > >> >> atom
> > >> >> > is it referring to? Like the nitrogen attached to C2 in a
> > carbohydrate
> > >> >> > derivative?
> > >> >> >
> > >> >> > Thanks for any advice.
> > >> >> >
> > >> >> > Regards,
> > >> >> >
> > >> >> > Yun
> > >> >> > _______________________________________________
> > >> >> > 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
> > >>
> > >> _______________________________________________
> > >> 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
> >
> > _______________________________________________
> > AMBER mailing list
> > AMBER.ambermd.org
> > http://lists.ambermd.org/mailman/listinfo/amber
> >
> >
> > _______________________________________________
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> >
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Received on Mon Sep 19 2011 - 15:30:05 PDT
