Hi Francois,
On Thu, Aug 25, 2011 at 11:20 AM, Yun Shi <yunshi09.gmail.com> wrote:
> 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)
>
> I did both in the way suggested above (since the sugar is linked to another
sugar ring via O3), modified the p2n file so as to include charge
constraints and remove caps.
Could you tell what the REORIENT means? What kind of atoms should be
reoriented?
And it seems that when I submit an ASP with sidechain de-prontonated, Ante
R.E.D. does not recognize the charged sidechain, so I guess I should modify
the CHARGE-VALUE and MULTIPLICITY-VALUE accordingly.
In the end, I should use the script provided by F85 (script1.ff?) to convert
the charged mol2 file to an OFF file, right? Since my fragments are not
standard residues in GLYCAM or 99SB, I should load GAFF in the script?
Regards,
Yun
> Yun
>
>
>
> 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
>>>
>>>
>>>
>>> _______________________________________________
>>> 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
Received on Thu Aug 25 2011 - 22:30:03 PDT
