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
Received on Tue Sep 11 2012 - 00:30:03 PDT
