Dear Prof. Simmerling,
Thanks for the reply.
The Gly I want to mutate has the plenty of space around it and its phi
and psi are in most stable conformation.
How exactly can I make this mutation using mm_pbsa.pl or any other method.
I will be very thankful for your kind response.
Manoj
On Mon, Nov 9, 2009 at 10:13 AM, Carlos Simmerling
<carlos.simmerling.gmail.com> wrote:
>
> Leap uses the connectivity tree information in the library about bond
> lengths, angles and default dihedral angles. making Gly into Ala is
> straightforward in the sense that there is no ambiguity about where to put
> the heavy atoms, but as Jason said it may well be that there is no room for
> the Cbeta, and in reality the structure would relax to accommodate it.
> instead you might get unreasonably high energies.
>
>
> On Sun, Nov 8, 2009 at 3:16 PM, Jason Swails <jason.swails.gmail.com> wrote:
>
> > Hello,
> >
> > There are no scripts in the amber distribution that will do this mutation
> > for MM-PBSA to use with alanine scanning. The only way to make this
> > mutation is to create a PDB (you can use ambpdb), change GLY to ALA at the
> > desired residue (deleting the hydrogens attached to CA) and loading the
> > structure into leap. Leap will add the other atoms, but I don't know what
> > algorithm it uses to do so.
> >
> > Good luck,
> > Jason
> >
> > On Sun, Nov 8, 2009 at 2:14 PM, manoj singh <mks.amber.gmail.com> wrote:
> >
> > > Thanks for your reply.
> > >
> > > I understand the Gly can attain all PHI and PSI values, however other
> > amino
> > > acids can not. But, if the Gly is in "usual" conformation, is it possible
> > > to
> > > mutate it to Ala using any available technique/script in the process of
> > > performing MM-PBSA.
> > >
> > > One more thing, when talking about electrostatic energy, one should not
> > > forget desolvation energy.
> > >
> > > Manoj
> > >
> > >
> > > On Sun, Nov 8, 2009 at 12:53 PM, Jason Swails <jason.swails.gmail.com
> > > >wrote:
> > >
> > > > Hello,
> > > >
> > > > You can write your own script/program to do the transformation. Soon
> > > there
> > > > will be a release of a new MM-PB(GB)SA script for amber that should be
> > > > faster and more user-friendly (and should handle alanine-scanning more
> > > > easily). However, even this new script does not handle Gly-Ala
> > mutations
> > > > since this is more complex than every other mutation. For every other
> > > > residue, all that is needed to handle an alanine mutation is to remove
> > > > extraneous atoms and readjust some bond lengths to match those in
> > > alanine.
> > > > Glycine is the only amino acid that has fewer atoms than alanine, so in
> > > > order to perform that mutation, atoms would need to be added to the
> > > system.
> > > > This is non-trivial, because the question becomes "where do we add
> > those
> > > > extra atoms?" (Ala has more degrees of freedom than Gly)
> > > >
> > > > It may even be the case that in a specific conformation, an alanine
> > would
> > > > not even fit where there's a glycine, so you would get an unphysically
> > > high
> > > > penalty for mutating that residue. Thus, the short version, there is
> > no
> > > > clear-cut, systematic way to handle a Gly->Ala mutation, so it's not
> > > done.
> > > >
> > > > Furthermore, alanine scanning is designed more to measure the
> > > electrostatic
> > > > (and perhaps VDW) effects that a particular sidechain has on the
> > activity
> > > > of
> > > > a protein. Glycine (and proline, though Pro->Ala is an allowed
> > mutation
> > > in
> > > > the upcoming version if not this one) more often serves a role in
> > > > modulating
> > > > the structure of a protein, so alanine scanning is often ill-suited to
> > > > probing the importance of a Glycine in the first place.
> > > >
> > > > Hope this helps,
> > > > Jason
> > > >
> > > > On Sun, Nov 8, 2009 at 12:25 PM, manoj singh <mks.amber.gmail.com>
> > > wrote:
> > > >
> > > > > Hi all!
> > > > >
> > > > > The mm_pbsa.pl can't do Gly->Ala mutation. Is there any way to do
> > this
> > > > > mutation in trajectory.
> > > > >
> > > > > Sincerely,
> > > > > _______________________________________________
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> > > > >
> > > >
> > > >
> > > >
> > > > --
> > > > ---------------------------------------
> > > > Jason M. Swails
> > > > Quantum Theory Project,
> > > > University of Florida
> > > > Ph.D. Graduate Student
> > > > 352-392-4032
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> > > > http://lists.ambermd.org/mailman/listinfo/amber
> > > >
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> > >
> >
> >
> >
> > --
> > ---------------------------------------
> > Jason M. Swails
> > Quantum Theory Project,
> > University of Florida
> > Ph.D. Graduate Student
> > 352-392-4032
> > _______________________________________________
> > AMBER mailing list
> > AMBER.ambermd.org
> > http://lists.ambermd.org/mailman/listinfo/amber
> >
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Received on Mon Nov 09 2009 - 08:30:06 PST
