Hi Francois,
As you said in the other email, I have to do validation no matter what kind
of parameters I choose. So I think, at least, I need to validate with the
conformational behavior of the per-OH-thiomethyl-Rhamnoside and the
per-OH-O-methyl-Rhamnoside.
But it seems that I need to build a disaccharide version for each case, so
that I could look at average phi and psi dihedral angles, average distances
between atoms on adjacent sugar rings, etc. But for the thiomethyl rhamnose,
what I could find are some nOes between protons on different sugar rings of
the S-disaccharide. So how to calculate normalized nOes from AMBER,
according to different mixing time?
And as you noted in the other email, the assignment of atom types for the
atom linking sugar part and amino acid part could be problematic. I think I
will use glycam atom types for the sulfur atom and the methylene attached,
since the validations would be with glycam force field (whether modified or
not).
It seems that the validation of thioglycosidic parameters in my case would
be very "indirect" using the S-disaccharide, but is there a better way?
By the way, I only have access to amber11, which did not come with glycam04
data files, which although I can get from the glycam website. But how can I
tell LEaP to use a specific data version such as Glycam_04k.dat (is this the
one you used with amber10)?
Thanks very much,
Yun
On Mon, Sep 19, 2011 at 4:23 AM, FyD <fyd.q4md-forcefieldtools.org> wrote:
> Dear Yun,
>
> > I have attached another charge constraints scheme here. So do you mean I
> > should derive charges from both fashions, and then calculate the average
> > charges for each atoms?
>
> I also agree with your second drawing - I even might prefer this one ;-)
>
> Among the two approaches I would select the one where the errors
> introduced (because of use of the constraints applied during the
> fitting step for the definition of the molecular fragments) are the
> smallest ones. The statistics module of R.E.D. Server reports these
> errors (see the Mol_MM/stat-RESP-FIT_mm file).
>
> > Sorry I still cannot find the database version of Glycam04 and glycam06
> > within the cyclodextrin paper and its Supporting information.
>
> Look for the 'version' word in the entire manuscript: we used
> GLYCAM06c and look at the versions up to f... As we used Amber10,
> GLYCAM04 came from Amber10... Yes, you are right this is difficult not
> to be lost between all these force field versions; this is why you can
> get the frcmod files used directly from the R.E.DD.B. project.
>
> regards, Francois
>
>
> > On Fri, Sep 16, 2011 at 3:42 AM, FyD <fyd.q4md-forcefieldtools.org>
> wrote:
> >
> >> Dear Yun,
> >>
> >> > 1.
> >> > Please see attached my charge-derivation scheme for one of the
> >> thiol-linked
> >> > 'glycopeptides', where I have two red intermolecular charge
> constraints
> >> and
> >> > one blue intra-molecular charge constraint set to 0.
> >>
> >> ok
> >>
> >> You might also try per-OH-methyl-glycoside versions instead of the
> >> hemiacetal monosaccharide units...
> >>
> >> > I will have 2 conformations for each sugar molecule respectively, and
> >> maybe
> >> > 3 for the modified TRP. Does this look OK?
> >>
> >> ok - if you care you will have to choose among various set of
> >> intra-monosaccharide hydrogen bonds...
> >>
> >> > I will follow the so-called
> >> > multi-molecule multi-conformation approach?
> >>
> >> ok
> >>
> >> > 2.
> >> > Which .dat version of GLYCAM04 was used for developing q4md-CD and
> >> testing
> >> > in the cyclodextrin paper? And GLYCAM06 version?
> >>
> >> I think the GLYCAM versions used/compared are reported in the
> manuscript.
> >>
> >> See also the F-85 R.E.DD.B. project
> >> . http://q4md-forcefieldtools.org/REDDB/projects/F-85/
> >> + its leaprc script + frcmod file:
> >> http://q4md-forcefieldtools.org/REDDB/projects/F-85/script1.ff
> >> http://q4md-forcefieldtools.org/REDDB/projects/F-85/script3.ff
> >>
> >> > 3.
> >> > I tried deriving charges with R.E.D. server for one molecule. Without
> any
> >> > constraint, I found that the total charge of every single atom within
> >> this
> >> > molecule is 0.0004 e. Is this normal?
> >>
> >> The RESP program generates charge values with 6 digits after the
> >> decimal point; the rounding off procedure to get charge values with 4
> >> digits is responsible for this 0.0000 +/-0.000X error.
> >>
> >> > It seems the RRMS value can be used to see how close the derived
> charges
> >> fit
> >> > the ESP, but where should I find this value when running charge
> >> derivation
> >> > with R.E.D. server?
> >>
> >> See the RESP output: I just ran a RESP-C2 demonstration job for a 10
> >> molecule jobs .
> >> http://q4md-forcefieldtools.org/REDS/RED-Server-demo1.php
> >>
> >> The data are .
> >>
> >>
> http://cluster.q4md-forcefieldtools.org/~ucpublic1/ADF1ADFaEsVIQjKADFDv89a14yM0ugjuejf03srADF/P3540.html
> >>
> >> The RESP output (single RESP stage fitting procedure) for the 10
> >> molecule charge derivation is .
> >>
> >>
> http://cluster.q4md-forcefieldtools.org/~ucpublic1/ADF1ADFaEsVIQjKADFDv89a14yM0ugjuejf03srADF/P3540/Data-R.E.D.Server/Mol_MM/output1_mm
> >>
> >> the RRMS value is:
> >> ESP relative RMS (SQRT(chipot/ssvpot)) 0.18989
> >>
> >> regards, Francois
> >>
> >>
> >> > On Tue, Sep 13, 2011 at 8:46 AM, FyD <fyd.q4md-forcefieldtools.org>
> >> wrote:
> >> >
> >> >> Yun,
> >> >>
> >> >> > And GLYCAM used different charges for alpha and beta anomers, so
> >> should I
> >> >> > stick to this even if I am using the 'amber' strategy?
> >> >>
> >> >> You do not 'need' to stick to this: you simply use two different
> >> >> building blocks: one is alpha and the other is beta; in these
> >> >> conditions, this is normal that by fitting to the MEP you get two
> >> >> different charge values for the alpha and beta anomers...
> >> >>
> >> >> regards, Francois
> >> >>
> >> >>
> >> >> > On Mon, Sep 12, 2011 at 11:32 PM, Yun Shi <yunshi09.gmail.com>
> wrote:
> >> >> >
> >> >> >> Hi Francois,
> >> >> >>
> >> >> >> I am worried since I saw no atom names information in the gaussian
> >> input
> >> >> >> file, which I used to do geometry optimization. I guess I should
> >> >> construct
> >> >> >> the gaussian input file from the xxx.pdb file generated by
> >> Ante_R.E.D.,
> >> >> then
> >> >> >> do my geometry optimization, then submit the gaussian out file
> >> together
> >> >> with
> >> >> >> xxx.p2n for charge derivation. So would there be any problem by
> doing
> >> >> so?
> >> >> >>
> >> >> >> In addition, I have only two major conformations for my small test
> >> >> molecule
> >> >> >> after QM geometry optimizations. So I wonder if I could just
> >> construct a
> >> >> >> merged p2n file with pdb coordinates from the two major
> QM-optimized
> >> >> >> conformers? I don't quite understand why R.E.D. server need QM
> >> >> optimization
> >> >> >> output file.
> >> >> >>
> >> >> >> Looking through the 'q4md-CD' paper, I feel it kind of
> >> counter-intuitive
> >> >> to
> >> >> >> mix GLYCAM04 geometrical parameters with atomic charges from
> 'Amber'
> >> >> >> strategy, which however, reproduced experimental data so well. But
> >> now I
> >> >> >> feel like that the RESP charges come hand-in-hand with the scaling
> >> >> factor,
> >> >> >> and I guess using the amber scaling factors is the major reason
> that
> >> >> your
> >> >> >> charge-derivation approach is successful.
> >> >> >>
> >> >> >> Since my molecule (the thio-glycosidic part) has no reference to
> look
> >> >> for
> >> >> >> experimental data to compare, what would be a simple experiment to
> >> carry
> >> >> out
> >> >> >> to validate my parameters? Or just try fitting them to QM
> >> calculations?
> >> >> >>
> >> >> >> By the way, what do you mean by " 'recompute' key dihedrals" when
> >> taking
> >> >> >> parameters from GAFF? And which are key dihedrals?
> >> >> >>
> >> >> >> Thanks,
> >> >> >>
> >> >> >> Yun
> >> >> >>
> >> >> >>
> >> >> >>
> >> >> >> On Wed, Sep 7, 2011 at 11:57 PM, FyD <
> fyd.q4md-forcefieldtools.org>
> >> >> wrote:
> >> >> >>
> >> >> >>> Dear Yun,
> >> >> >>>
> >> >> >>> > I basically understand this approach now. But for this
> >> >> >>> Rha-S-CH2-CH(R)-NH-
> >> >> >>> > group, how should I deal with the N terminus? If I simply add
> an
> >> ACE
> >> >> cap
> >> >> >>> to
> >> >> >>> > make it Rha-S-CH2-CH(R)-NH-ACE,
> >> >> >>>
> >> >> >>> Yes, with a trans peptide bond:
> >> >> >>>
> >> >> >>> H
> >> >> >>> Rha-S-CH2-CH(R)-N-C-Me
> >> >> >>> O
> >> >> >>>
> >> >> >>> > then how to set charge constraints?
> >> >> >>>
> >> >> >>> You set a single INTRA-MCC = 0 for the ACE chemical group in the
> P2N
> >> >> file.
> >> >> >>>
> >> >> >>> See http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php#15
> >> >> >>> (However in this #15 example two capping groups are added, so two
> >> >> >>> INTRA-MCC are set in the P2N file; In your case, you need to set
> a
> >> >> >>> single INTRA-MCC in your P2N file).
> >> >> >>>
> >> >> >>> > Should I
> >> >> >>> > add a Met or a Hydrogen to O3 on Rha? Because CENTRAL fragments
> >> >> instead
> >> >> >>> of
> >> >> >>> > TERMINNAL fragments are needed here.
> >> >> >>>
> >> >> >>> So you need two L-Rhamnoside building blocks...
> >> >> >>> a perOH-thiomethyl-Rhamnoside & a perOH-O-methyl-Rhamnoside
> >> >> >>>
> >> >> >>> [You could also try a different set of connecting groups between
> >> >> >>> S/O-hemiacetals (instead of S/O-acetals) and methoxy groups (i.e.
> >> >> >>> ether groups instead of hydroxyl groups).
> >> >> >>>
> >> >> >>> > Sorry our library does not have access to the Cieplak et al.
> >> paper.
> >> >> >>>
> >> >> >>> ok, I will send you the pdf file to your personal address (I
> think
> >> the
> >> >> >>> license to publish exclude the free distribution of this
> paper)...
> >> >> >>>
> >> >> >>> > In addition, I noted that GLYCAM06 have exactly the same
> charges
> >> for
> >> >> >>> most
> >> >> >>> > atoms in the same sugar molecule with different linkage, i.e.,
> >> >> >>> > 2-L-alpha-Rhamnose share identical atomic charges with
> >> >> >>> 3-L-alpha-Rhamnose
> >> >> >>> > except O2 and O3. However in amber99sb, every corresponding
> single
> >> >> atom
> >> >> >>> of,
> >> >> >>> > say TRP, would have different charges from ntTRP. I guess this
> may
> >> >> have
> >> >> >>> > something to do with the charge-deriving methods, as
> >> qwt=0.0005/0.001
> >> >> in
> >> >> >>> > 99sb VS qwt=0.01 in GLYCAM.
> >> >> >>>
> >> >> >>> This has to do with the charge constraints applied during the
> charge
> >> >> >>> fitting step.
> >> >> >>>
> >> >> >>> > But then the question would be, should I set charge constraints
> to
> >> >> most
> >> >> >>> > atoms on the sugar ring except the anomeric carbon and derive
> >> charges
> >> >> >>> using
> >> >> >>> > RESP-C2 for the sugar part, which would allow me to avoid the
> use
> >> of
> >> >> the
> >> >> >>> > first Rhamnose? Or just do all charges with RESP-A1A?
> >> >> >>>
> >> >> >>> Well you are right; this is the key ;-)
> >> >> >>>
> >> >> >>> -1- I guess GLYCAM developers will suggest you to use something
> >> >> >>> similar to the RESP-C2 charge model; i.e. MEP computation using
> the
> >> >> >>> CHELPG algo. and a single RESP fitting stage using the qwt=.01
> >> >> >>> hyperbolic restraint. This means using 1.0 scaling factors for
> the
> >> 1-4
> >> >> >>> non-bonding interactions for the sugar part of your ligand and
> >> 1.2/2.0
> >> >> >>> for the other part. Quite complex... considering the size of your
> >> >> >>> ligand and considering that the Connolly surface algorithm is
> used
> >> in
> >> >> >>> MEP computation and a two RESP stage fitting approach is used for
> >> the
> >> >> >>> non-sugar part.
> >> >> >>>
> >> >> >>> -2- Considering that L-Rhamnose is the 6-deoxy-L-mannose, I would
> >> >> >>> follow the approach we described .
> >> >> >>> http://www.ncbi.nlm.nih.gov/pubmed/21792425/ for all your ligand
> >> and
> >> >> >>> more general all your molecular system (in case of a Galacto
> >> >> >>> configuration I would suggest you to use the GLYCAM approach
> -1-).
> >> >> >>> This means 1.2/2.0 scaling factors for all the 1-4 non-bonding
> >> >> >>> interactions and using the Connolly surface algorithm in MEP
> >> >> >>> computation and a two RESP stage fitting approach for the entire
> >> >> >>> ligand. Far more simple... However, this approach has obviously
> to
> >> be
> >> >> >>> validated (however as it is requested for the case -1-).
> >> >> >>>
> >> >> >>> regards, Francois
> >> >> >>>
> >> >> >>>
> >> >> >>>
> >> >> >>> > On Sat, Aug 27, 2011 at 12:16 AM, FyD <
> >> fyd.q4md-forcefieldtools.org>
> >> >> >>> wrote:
> >> >> >>> >
> >> >> >>> >> Dear Yun,
> >> >> >>> >>
> >> >> >>> >> - When you have a peptide bond within a molecule, R1NH-COR2
> you
> >> >> could
> >> >> >>> >> split this molecule into two parts R1NH-ACE & NME-COR2 (ACE =
> >> CH3CO;
> >> >> >>> >> NME = NHCH3; are capping groups). You use two INTRA-MCC set to
> >> zero
> >> >> >>> >> for these capping groups:
> >> >> >>> >>
> >> >> >>> >> R.E.D.:
> >> >> >>> >> 2 FG2 fragments LEaP
> >> >> >>> >> R1NH-ACE + NME-COR2 --> R1NH COR2 ----->
> R1NH-COR2
> >> >> >>> >> <=> <=>
> >> >> >>> >> 2 INTRA-MCC = 0
> >> >> >>> >>
> >> >> >>> >>
> >> >> >>> >> - When you have a disaccharide R'-O-R", you could split it
> into
> >> two
> >> >> >>> >> monosaccharides by using an INTER-MCC set to zero between the
> >> methyl
> >> >> >>> >> group of the methylglycoside (building-block 1) and the chosen
> >> >> >>> >> hydroxyl group belonging to the second monosaccharide unit:
> >> >> >>> >>
> >> >> >>> >> R.E.D.:
> >> >> >>> >> R'O-Me HO-R" 2 FG1 fragments LEaP
> >> >> >>> >> <-----> ---> R'O R" -----> R'-O-R"
> >> >> >>> >> 1 INTERMCC = 0
> >> >> >>> >>
> >> >> >>> >> by analogy, you could test:
> >> >> >>> >>
> >> >> >>> >> R'S-Me HS-R"
> >> >> >>> >> <-----> ---------------> R'-S-R"
> >> >> >>> >> 1 INTERMCC = 0
> >> >> >>> >>
> >> >> >>> >> With these simples rules you can split your red-blue-red-green
> >> >> >>> >> molecule into 4 building blocks.
> >> >> >>> >>
> >> >> >>> >> These have been defined some time ago; see
> >> >> >>> >> http://q4md-forcefieldtools.org/Tutorial/Tutorial-1.php
> >> >> >>> >> &
> >> >> >>> >> Cieplak et al. Application of the multimolecule and
> >> >> >>> >> multiconformational RESP methodology to biopolymers: Charge
> >> >> derivation
> >> >> >>> >> for DNA, RNA, and proteins. J. Comput. Chem. 1995, 16,
> 1357-1377.
> >> >> >>> >>
> >> >> >>> >> With R.E.D. Server/R.E.D. IV you can generate all these
> fragments
> >> >> into
> >> >> >>> >> a single R.E.D. job by using the corresponding P2N files and
> by
> >> >> >>> >> defining the correct constraints during the charge fitting
> step.
> >> >> >>> >> See http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php
> >> >> >>> >> &
> http://q4md-forcefieldtools.org/Tutorial/Tutorial-3.php#29
> >> >> >>> >>
> >> >> >>> >> regards, Francois
> >> >> >>> >>
> >> >> >>> >>
> >> >> >>> >> Quoting Yun Shi <yunshi09.gmail.com>:
> >> >> >>> >>
> >> >> >>> >> > Sorry that I should have attached this model molecule I want
> to
> >> >> study
> >> >> >>> >> > earlier.
> >> >> >>> >> >
> >> >> >>> >> > As you can see, I divide this ligand into four parts, and
> the
> >> >> >>> parameters
> >> >> >>> >> > (atomic charges, bonds, angles, dihedrals, impropers) of the
> >> red
> >> >> >>> >> (terminal)
> >> >> >>> >> > sugar and green ASP can be obtained from GLYCAM and 99SB
> >> >> >>> respectively.
> >> >> >>> >> >
> >> >> >>> >> > But I have to include the glycosidic oxygen between two
> sugar
> >> >> rings
> >> >> >>> in
> >> >> >>> >> the
> >> >> >>> >> > blue thio sugar, as this glysicidic oxygen is defined in the
> >> >> >>> preceding
> >> >> >>> >> sugar
> >> >> >>> >> > (the blue thio sugar) instead of the succeeding sugar
> according
> >> to
> >> >> >>> >> GLYCAM.
> >> >> >>> >> >
> >> >> >>> >> > I plan to use the approach -2- you mentioned (so that I
> don't
> >> need
> >> >> >>> >> generate
> >> >> >>> >> > many conformations), but considering my specific case, I
> wonder
> >> >> why
> >> >> >>> not
> >> >> >>> >> > using
> >> >> >>> >> >
> >> >> >>> >> > Me-O3-L-RhamnoS-Me + MeS-CH2CH(R)NH-COMe
> >> >> >>> >> > <----------------------> <===========>
> >> >> >>> >> > INTER-MCC=0 INTRA-MCC=0
> >> >> >>> >> >
> >> >> >>> >> > , and then remove the Me - Me and MeS - COMe respectively?
> >> >> >>> >> >
> >> >> >>> >> > Since the L-Rha and TRP in my case carry only one modified
> site
> >> >> >>> compared
> >> >> >>> >> to
> >> >> >>> >> > their standard counterparts, should I include charge
> >> constraints
> >> >> >>> (keep
> >> >> >>> >> the
> >> >> >>> >> > atomic charges) for atoms far away from the modified sites?
> >> Such
> >> >> as
> >> >> >>> C5
> >> >> >>> >> and
> >> >> >>> >> > C6 in the thio sugar, and the entire indole ring of the
> >> modified
> >> >> TRP?
> >> >> >>> >> >
> >> >> >>> >> > Thank you so much!
> >> >> >>> >> >
> >> >> >>> >> > Yun
> >> >> >>> >> >
> >> >> >>> >> >
> >> >> >>> >> > On Thu, Aug 25, 2011 at 11:37 PM, FyD <
> >> >> fyd.q4md-forcefieldtools.org>
> >> >> >>> >> wrote:
> >> >> >>> >> >
> >> >> >>> >> >> 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 Tue Sep 20 2011 - 21:30:02 PDT
