Dear Carlos,
I am very much interested in this DNA resequencing program for my
NMR/computational studies of various drug-DNA complexes. Whats the best way
to get access to it ?
Many Thanks!
-Rupesh
On Wed, Sep 12, 2012 at 1:20 PM, Carlos Simmerling <
carlos.simmerling.gmail.com> wrote:
> sure- if anyone wants my DNA resequencing program, contact me off the list.
> maybe we can include it in the future amber versions- but it's fairly
> basic.
>
>
>
> On Tue, Sep 11, 2012 at 6:06 AM, vaibhav dixit <vaibhavadixit.gmail.com
> >wrote:
>
> > That's great! Can this program be made available for academic use?
> >
> > On Tue, Sep 11, 2012 at 3:20 PM, Carlos Simmerling <
> > carlos.simmerling.gmail.com> wrote:
> >
> > > 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
> > > > > > > > > >
> > > > > > > > > _______________________________________________
> > > > > > > > > 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
> > > > >
> > > >
> > > >
> > > >
> > > > --
> > > > 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
> > >
> >
> >
> >
> > --
> > 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
> >
> _______________________________________________
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>
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Received on Wed Sep 12 2012 - 10:30:06 PDT
