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,
> > > > _______________________________________________
> > > > AMBER mailing list
> > > > AMBER.ambermd.org
> > > > http://lists.ambermd.org/mailman/listinfo/amber
> > > >
> > >
> > >
> > >
> > > --
> > > ---------------------------------------
> > > 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
> > >
> > _______________________________________________
> > AMBER mailing list
> > AMBER.ambermd.org
> > http://lists.ambermd.org/mailman/listinfo/amber
> >
>
>
>
> --
> ---------------------------------------
> 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 - 07:30:02 PST
