Hi
Though I am no expert but the biggest issue which I see which you have
addressed below is *sampling*. There have been many debates on whether one
long simulation or many short simulations with different initial seeds will
give you better sampling. In my opinion both approaches have their pros and
cons so might want to research some papers which address this issue.
This is a website which goes over Energy Decomposition:
http://ambermd.org/tutorials/advanced/tutorial3/py_script/section6.htm
On Fri, Jun 4, 2010 at 11:03 AM, Sushil Mishra <sushilbioinfo.gmail.com>wrote:
> Thanks a lot for the response !
> Yes I am getting fluctuation in binding energy by making the R17A mutation
> but it is quite high change (about + 14 Kcal/mol). although I am trying to
> repeat the calculation with much longer trajectory (15ns) and with more
> number of snapshots (500 for each) so to avoid the problem of sampling. Can
> u point out some issue which should be considered carefully during this
> type
> of calculation ? could u direct me in any tutorial or paper regarding per
> residue decomposition of free energy ?
>
> Regards
> Sushil
>
> On Fri, Jun 4, 2010 at 4:52 PM, Dwight McGee <dwight.mcgee.gmail.com>
> wrote:
>
> > Hi
> >
> > Based off the information below I would say yes to your approach. If
> you
> > see a fluctuation in the binding energy from making the R17A mutation
> than
> > you know whether or not that particular residue has an important
> > contribution to the binding free energy. I am not aware of any tutorials,
> > which demonstrate this using the mm_pbsa.pl though they might exist.
> There
> > is however a tutorial demonstrating this using MMPBSA.py. No matter how
> > many
> > mutations you make at once it will only return back one free energy. You
> > may
> > want to look at doing Energy Decomposition because this will give you a
> > better breakdown of each residue's contribution to the free energy.
> > Good Luck
> >
> > On Thu, Jun 3, 2010 at 1:09 PM, Sushil Mishra <sushilbioinfo.gmail.com
> > >wrote:
> >
> > > Hi all,
> > >
> > > I would like to share some experiences, with researchers tried Alanine
> > > scanning mutagenesis using mm_pbsa.pl in amber 10. I am writing the
> > steps
> > > I
> > > tried to attempt the problem (R17A mutation).
> > >
> > > 1 - I run a 20ns production run of protein with 12 A water box.
> > > 2- run MM/PBSA calculation with wild type.
> > > 3 - Then I mutated Arg17 in to Ala17 and created .prmtop and .inpcrd
> file
> > > of
> > > the mutated protein
> > > 4 - I used that this prmtop file of complex and protein to run MM/PBSA
> > > again. This time i used AS=1 and in .ALASCAN section i putted all the
> > > information regarding mutation of Arg17 in to Ala17. As this info was
> > > passed
> > > to make_crd_hg and snapshot generated with these parameters were having
> > > Ala17, so i used prmtop file fof rec and complex generated in step 3
> for
> > > calculation of free MM/PBSA.
> > > 5- Now i compare the delta PBTOT of MM/PBSA run in wild type and delta
> > > PBTOT
> > > of MM/PBSA in mutant (R17A).
> > >
> > > Is the the correct way i used to find the change in free energy when
> Arg
> > 17
> > > was mutated in Ala17 ?
> > > can u direct me to some tutorial where this thing have been tried with
> > perl
> > > script ?
> > > As i read in manual it is possible to maximum 40 mutations in single
> run
> > > but
> > > will it return delta PBTOT of all 40 mutation at a time, or separately
> of
> > > each one mutation at a time and for all 40 such mutatation?
> > >
> > > Regards
> > > ..Sushil
> > > _______________________________________________
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> > > AMBER.ambermd.org
> > > http://lists.ambermd.org/mailman/listinfo/amber
> > >
> >
> >
> >
> > --
> > T. Dwight McGee Jr.
> > Quantum Theory Project
> > University of Florida
> > dwight.mcgee.gmail.com
> >
> > "Problems cannot be solved at the same level of awareness that created
> > them."
> > Albert Einstein
> > _______________________________________________
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> > http://lists.ambermd.org/mailman/listinfo/amber
> >
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>
--
T. Dwight McGee Jr.
Quantum Theory Project
University of Florida
dwight.mcgee.gmail.com
"Problems cannot be solved at the same level of awareness that created
them."
Albert Einstein
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Received on Fri Jun 04 2010 - 09:00:03 PDT
