Yun,
> Sorry, I just read the tutorial, that is, "Central fragment of a xxx".
>
> So for the modified (C-terminal reduced) amino acid, should I add a MeCO at
> the N-terminus and MeS at the reduced C-terminus? (considering the reduced
> C-terminus is used to link glycosidic sulfur atom).
>
> And for the sugar molecule, should I add a Me cap to 3-hydroxyl group in
> addition to a methyl group attached to the glycosidic sulfur? (This sugar
> molecule would fall into the category of central fragment of my ligand)
ups I overlooked your problem ;-) You do not have any cysteine residue...
Let's re-do the explanations with your terminal molecule/pseudo amino-acid:
-1- you consider the following molecule
Thio-L-Rhamno-CH2CH(R)NH-COMe ; R = CH2-Ph
<==>
INTRA-MCC
You only have to set up an intra-molecular charge constraint
(INTRA-MCC keyword) for the COMe capping group (see <==> above).
See
http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php#15
R.E.D. will generate a sm fragment (mol2 file) for you.
-2- you split your molecule into two building blocks.
L-RhamnoS-Me + HS-CH2CH(R)NH-COMe
<-------> <==>
INTER-MCC INTRA-MCC
See
http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php#16
or
http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php#17
You set up an intra-molecular charge constraint (INTRA-MCC keyword)
for the COMe capping group.
You set up an inter-molecular charge constraint (INTER-MCC keyword)
between the methyl group of L-RhamnoS-Me and the thiol group of your
pseudo terminal amino-acid.
The approach -2- is once again more complex but more flexible...
R.E.D. will generate a FG fragment (mol2 file) in the Mol_MM directory.
Sorry for misunderstanding your problem in my first email.
regards, Francois
> On Thu, Aug 25, 2011 at 9:58 AM, Yun Shi <yunshi09.gmail.com> wrote:
>
>> 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 Fri Aug 26 2011 - 00:00:02 PDT
