Thank you very much!
I looked at the CD project, and I saw when FFTopDB were constructed, the
1-metylated glucose was used to derive RESP charges. So in my
thio-glycopeptide case, should I use the sugar molecule with a methyl group
attached to the glycosidic sulfur as well?
What about the modified (C-terminal reduced) amino acid? Add one more
methyl group to the modified C-terminal and acetate to the N-terminal?
But in the end, what is deposited in the FFTopDB is the residue without the
methyl or acetate cap, right?
Yun
On Wed, Aug 24, 2011 at 11:38 PM, FyD <fyd.q4md-forcefieldtools.org> wrote:
> Dear Yun Shi,
>
> > I am trying to understand how this works.
>
> If you look at the data available in the "F-85" R.E.DD.B. project, you
> will find a x/tLEaP script to construct the CD-based glycopeptides as
> well as a frcmod file for missing force field parameters with comments.
> http://q4md-forcefieldtools.org/REDDB/projects/F-85/script1.ff
> http://q4md-forcefieldtools.org/REDDB/projects/F-85/script3.ff
>
> > So instead of combining individual residues in a building-block manner,
> as
> > in the assignment of atomic charges for proteins with amber99sb, it is
> > recommended to consider the ligand as a holistic molecule when
> calculating
> > the RESP charge?
>
> 'recommended'? ;-) ... Personally, I use most of the time the building
> block approach whatever if the target 'big' molecule is a ligand or a
> nucleic acid/protein/polysacharide.
>
> > I am curious that if I could do things in a building-block
> > manner since it can potentially decrease a lot of computational time for
> > geometry optimization.
>
> The building-block approach has many advantages:
> - it potentially "decreases a lot of computational time for geometry
> optimization" as you said.
> - it allows rigorously defining the conformation of each
> building-block and not to use a conformation more or less randomly
> chosen.
> - it allows avoiding interactions between charges group during
> geometry optimization in gas phase.
> - it allows the construction of analogs for the target molecule.
> - it allows the construction of oligomers/polymers for the target molecule.
>
> However, it also has disadvantages:
> - it is complex to set up when one starts, but R.E.D. has been
> designed for this approach.
> - errors during the charge fitting step are introduced when using the
> building-block approach; these errors have to be minimized by
> correctly selecting the connecting groups between the different
> building-blocks. The statistics module available in R.E.D.
> Server/R.E.D. IV also helps to localize/minimize these errors.
>
> > And when it comes to geometrical parameters, we should use GLYCAM for
> sugar
> > part, 99SB for standard amino acids, and GAFF for organic part?
>
> Yes
>
> - We only select 'obvious' missing force field parameters from GAFF
> (we recompute key dihedrals), and when used we always rationalize
> these force field parameters as it was done in the Cornell at al.
> force field.
>
> - In this work, we used Amber scaling factor values for 1-4
> non-bonding interactions for all the glycopeptide molecular systems;
> i.e. we did not split the system into a peptide and a sugar parts.
>
> > BTW, could you tell me how to generate multiple conformations with
> geometry
> > optimization from Gaussian 09?
>
> You could do a conformational search - although if the building-block
> approach is used the conformational search is quite simplified...
> We also often modify a key dihedral to look for lowest minimum/minima.
>
> To create a P2N file with multiple conformations, see:
> http://q4md-forcefieldtools.org/Tutorial/Tutorial-1.php#3
> http://q4md-forcefieldtools.org/Tutorial/Tutorial-1.php#EXAMPLE-P2N-FILE
>
> To create a QM file with multiple conformations to be used in the Mode
> 2 of R.E.D. (see
> http://q4md-forcefieldtools.org/REDS/popup/popredmodes.php), simply
> concatenate the different QM outputs into a single file.
>
> regards, Francois
>
> >> Dear Yun,
> >>
> >> > 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
> >> > ?
> >>
> >> Concerning the use of GLYCAM + GAFF + Amber99SB you might be
> >> interested by looking at the following paper:
> >> http://www.ncbi.nlm.nih.gov/pubmed/21792425
> >> & its corresponding R.E.DD.B. project .
> >> http://q4md-forcefieldtools.org/REDDB/projects/F-85/ + its LEaP script:
> >> http://q4md-forcefieldtools.org/REDDB/projects/F-85/script1.ff
> >>
> >> This work is about cyclodextrin based-glycopeptide and 1-4 non-bonding
> >> interactions in GLYCAM & Amber99SB.
> >>
> >> Your structure is not a cyclodextrin but this work describe (i) how to
> >> derive charges and build force field libraries for new fragments by
> >> using R.E.D. IV and (ii) proposes new directions concerning the
> >> treatment of 1-4 non-bonding interactions in the context of
> >> glycopeptides.
> >>
> >> Finally, in the LEaP script you will find examples how to connect
> >> organic, amino-acid and monosaccharide units...
> >>
> >> regards, Francois
>
>
>
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Received on Thu Aug 25 2011 - 10:00:02 PDT
