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 - 00:00:02 PDT
