yes this is easier- I've even written a program that resequences the DNA by
keeping the common atoms between old and new base and renaming them so leap
builds the rest. of course you can still get clashes, such as with purine
pairs, but at least it gives you a structure to start.
On Mon, Sep 10, 2012 at 11:35 PM, Aron Broom <broomsday.gmail.com> wrote:
> I've never done this, but I would imagine this is a far simpler problem
> than the amino acid one, since the orientation of the bases should remain
> the same. Perhaps in this scenario the LEaP method would actually work
> just fine?
>
> On Mon, Sep 10, 2012 at 10:52 PM, vaibhav dixit <vaibhavadixit.gmail.com
> >wrote:
>
> > 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?
> > Thanks for your suggestions in advance.
> >
> > 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
> > > > > > >
> > > > > > _______________________________________________
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> > > > > >
> > > > >
> > > > >
> > > > >
> > > > > --
> > > > > 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
> > > > >
> > > > _______________________________________________
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> > > > AMBER.ambermd.org
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> > > >
> > >
> > >
> > >
> > > --
> > > 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
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> > http://lists.ambermd.org/mailman/listinfo/amber
> >
>
>
>
> --
> Aron Broom M.Sc
> PhD Student
> Department of Chemistry
> University of Waterloo
> _______________________________________________
> AMBER mailing list
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>
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Received on Tue Sep 11 2012 - 03:00:03 PDT
