Dear Dr. Francois,
Thanks for highlighting these points and giving relevant links.
I will try to understand and use these tools soon, and get back if I have
more doubts.
On Tue, Sep 11, 2012 at 12:54 PM, FyD <fyd.q4md-forcefieldtools.org> wrote:
> Dear Vaibhav Dixit,
>
> > If I have a DNA or RNA lets say dodecamer, how can I mutate it? Means how
> > can I replace A with G or T with C?
>
> See the former email I sent about the t/xLEaP program and the answer
> from Bill.
>
> You follow the same approach for a modified nucleotide residue than
> for a mutated amino acid residue. You remove the base and rename the
> residue name for the ribose derivative according to the residue name
> defined in the FF library for the mutated/modified nucleotide. x/tLEaP
> will do the job and add the missing atoms for the modified residue.
>
> To convince Carlos (if one needs to) LEaP has a geometry optimizer
> (all structure or selected parts), can invert chirality center and
> modify dihedral angle values to correct the generated modification.
> Most of these commands were only available in xLEaP; at
> q4md-forcefieldtools.org we have introduced them in tLEaP allowing to
> make these commands 'scriptable'...
> See http://q4md-forcefieldtools.org/Tutorial/Tutorial-1.php
> http://q4md-forcefieldtools.org/Tutorial/leap-mol2.php
>
> The strength of LEaP (I mean x/t) is that it is free (sense of
> freedom), it is directly usable (when one has installed the
> AmberTools) and very powerful (when one uses it the correct way);
> obviously one needs to understand how it works (may be not that easy).
>
> regards, Francois
>
>
> > On Tue, Sep 11, 2012 at 6:02 AM, Aron Broom <broomsday.gmail.com> wrote:
> >
> >> Yikes, point taken.
> >>
> >> Also for anyone who finds this thread, PyMol has a mutation function
> that
> >> uses a rotamer library.
> >>
> >> ~Aron
> >>
> >>
> >> On Mon, Sep 10, 2012 at 6:24 PM, Carlos Simmerling <
> >> carlos.simmerling.gmail.com> wrote:
> >>
> >> > what often happens in my experience is that the steric clashes are bad
> >> > enough that the atoms get pushed around, and the chirality inverts
> >> because
> >> > of that. eventually you minimize the clash away, but in the process
> >> things
> >> > are no longer correct. we've even seen really weird cases such as
> where a
> >> > Phe ended up with a protein chain going through the middle of the
> ring-
> >> > obviously no way that will ever get fixed in MD.
> >> >
> >> > I guess I'm just warning people that if you have a high energy
> structure,
> >> > just because you minimize it doesn't mean things are ok. you should
> >> always
> >> > visually inspect the area where you made the change.
> >> >
> >> >
> >> > On Mon, Sep 10, 2012 at 5:53 PM, Aron Broom <broomsday.gmail.com>
> wrote:
> >> >
> >> > > Just as an addition/question here concerning the LEaP approach: if
> you
> >> > > delete everything EXCEPT the backbone AND beta-carbon (or in the
> case
> >> of
> >> > > mutating glycine to something, just rename the "sidechain" hydrogen
> to
> >> a
> >> > > carbon) would LEaP then use that and thereby avoid the problem of
> >> messing
> >> > > up chirality or something extreme, and leave you only with the
> problem
> >> or
> >> > > steric clashes?
> >> > >
> >> > > If so, it's clearly not as ideal as using a program that has a
> rotamer
> >> > > library as has been suggested here, but still isn't devestating if
> you
> >> > are
> >> > > willing to do some minimization or something or the sort.
> >> > >
> >> > > ~Aron
> >> > >
> >> > > On Mon, Sep 10, 2012 at 4:30 PM, Jonathan Gough
> >> > > <jonathan.d.gough.gmail.com>wrote:
> >> > >
> >> > > > Thank you all for your help! Very good suggestions. I am using
> >> swiss
> >> > > PDB
> >> > > > right now.
> >> > > >
> >> > > > I said 3+ as I could think of at least 1 if not multiple more
> ways to
> >> > do
> >> > > it
> >> > > > (other applications or combinations of applications).
> >> > > >
> >> > > >
> >> > > >
> >> > > > On Mon, Sep 10, 2012 at 3:43 PM, Carmenza Martinez <
> >> crm3680.gmail.com
> >> > > > >wrote:
> >> > > >
> >> > > > > sorry I meant to say just as Prof. Simmerling said...the said
> got
> >> > > > > deleted...sorry
> >> > > > >
> >> > > > > On Mon, Sep 10, 2012 at 3:39 PM, Carmenza Martinez <
> >> > crm3680.gmail.com
> >> > > > > >wrote:
> >> > > > >
> >> > > > > > Not sure if anybody has suggested it previously but for single
> >> > point
> >> > > > > > mutations or multiple mutations of residues I have found
> swissPDB
> >> > to
> >> > > be
> >> > > > > > quite useful:
> >> > > > > > http://spdbv.vital-it.ch/
> >> > > > > > Just as Prof. Simmerling leap is not efficient at filling in
> the
> >> > > blanks
> >> > > > > > when you remove things and renamed them just as Francois
> >> suggested.
> >> > > > > > Now, when you say 3+???? I don't understand what you
> >> > mean...changing
> >> > > > the
> >> > > > > > protonation state perhaps? for that you will need more than
> what
> >> > > swiss
> >> > > > > PDB
> >> > > > > > could provide. Perhaps somebody else in the forum will provide
> >> > useful
> >> > > > > > advide for that
> >> > > > > > Best regards
> >> > > > > >
> >> > > > > >
> >> > > > > >
> >> > > > > > On Mon, Sep 10, 2012 at 3:01 PM, Carlos Simmerling <
> >> > > > > > carlos.simmerling.gmail.com> wrote:
> >> > > > > >
> >> > > > > >> This isn't a good method- leap doesn't care at all where it
> puts
> >> > the
> >> > > > > side
> >> > > > > >> chain and unless you're very lucky you will have bad steric
> >> > clashes
> >> > > > that
> >> > > > > >> can invert chivalry and other bad things. You want to use a
> >> > program
> >> > > > that
> >> > > > > >> searches rotamers for something that fits as best as
> possible.
> >> > > > > >> On Sep 10, 2012 2:48 PM, "FyD" <fyd.q4md-forcefieldtools.org
> >
> >> > > wrote:
> >> > > > > >>
> >> > > > > >> > Dear Jonathan,
> >> > > > > >> >
> >> > > > > >> > You could edit the PDB file: (i) remove the side chain of
> the
> >> > > amino
> >> > > > > >> > acid to be mutated; (ii) rename the backbone of this
> residue
> >> > > > according
> >> > > > > >> > to the residue name of the mutation. Then, you load the
> >> modified
> >> > > PDB
> >> > > > > >> > file in the LEAP program, which will automatically add the
> >> > missing
> >> > > > > >> > atoms (i.e. the side chain) in agreement with the FF
> library
> >> of
> >> > > the
> >> > > > > >> > mutated residue.
> >> > > > > >> >
> >> > > > > >> > regards, Francois
> >> > > > > >> >
> >> > > > > >> >
> >> > > > > >> > > The basic (or complex) question I have is:
> >> > > > > >> > >
> >> > > > > >> > > How do you take a PDB and change one residue to another
> >> > residue?
> >> > > > > >> > > (essentially a point mutation of an existing structure)
> >> > > > > >> > >
> >> > > > > >> > > I thought I remembered reading how it could be done, but
> >> > looking
> >> > > > > back
> >> > > > > >> I
> >> > > > > >> > > can't seem to find where it might be. I can think of a
> few
> >> > ways
> >> > > > one
> >> > > > > >> > could
> >> > > > > >> > > accomplish this, but I wanted to ask if there is an
> >> > explanation
> >> > > in
> >> > > > > the
> >> > > > > >> > > manual or a tutorial that I am just missing. (Can
> someone
> >> > point
> >> > > > me
> >> > > > > in
> >> > > > > >> > the
> >> > > > > >> > > right direction)
> >> > > > > >> > >
> >> > > > > >> > > 1. I searched the archives and saw some old posts
> regarding
> >> > > using
> >> > > > > >> other
> >> > > > > >> > > programs.
> >> > > > > >> > > 2. One could manually add/change things
> >> > > > > >> > > 3+????
> >> > > > > >> > >
> >> > > > > >> > > Not necessarily looking for a step by step but a push in
> the
> >> > > right
> >> > > > > >> > > direction.
> >> > > > > >> >
> >> > > > > >> >
> >> > > > > >> >
> >> > > > > >> > _______________________________________________
> >> > > > > >> > 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
> >> > > > > >>
> >> > > > > >
> >> > > > > >
> >> > > > > >
> >> > > > > > --
> >> > > > > > Carmenza Martinez
> >> > > > > >
> >> > > > > >
> >> > > > >
> >> > > > >
> >> > > > > --
> >> > > > > Carmenza Martinez
> >> > > > > _______________________________________________
> >> > > > > 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
> >> > > >
> >> > >
> >> > >
> >> > >
> >> > > --
> >> > > Aron Broom M.Sc
> >> > > PhD Student
> >> > > Department of Chemistry
> >> > > University of Waterloo
> >> > > _______________________________________________
> >> > > 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
> >> >
> >>
> >>
> >>
> >> --
> >> Aron Broom M.Sc
> >> PhD Student
> >> Department of Chemistry
> >> University of Waterloo
> >> _______________________________________________
> >> AMBER mailing list
> >> AMBER.ambermd.org
> >> http://lists.ambermd.org/mailman/listinfo/amber
> >>
> > --
> > With regards
> >
> > Vaibhav A. Dixit
> > Ph.D. Scholar
> > Department of Medicinal Chemistry
> > Natl. Inst. Pharm. Edu. & Res. (NIPER)
> > Sector 67, Phase X, S.A.S. Nagar (Mohali)
> > Punjab -160 062 INDIA
> > Phone (Mobile): +919915214408
> > E-mail: vaibhavadixit.gmail.com
> > www.niper.nic.in
>
>
>
> _______________________________________________
> AMBER mailing list
> AMBER.ambermd.org
> http://lists.ambermd.org/mailman/listinfo/amber
>
--
With regards
Vaibhav A. Dixit
Ph.D. Scholar
Department of Medicinal Chemistry
Natl. Inst. Pharm. Edu. & Res. (NIPER)
Sector 67, Phase X, S.A.S. Nagar (Mohali)
Punjab -160 062 INDIA
Phone (Mobile): +919915214408
E-mail: vaibhavadixit.gmail.com
www.niper.nic.in
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Received on Tue Sep 11 2012 - 01:30:03 PDT
