Very helpful.
As always, thanks Jason!
On Mon, Dec 17, 2012 at 8:10 PM, Jason Swails <jason.swails.gmail.com>wrote:
> The idea of computational alanine scanning is that a mutating single
> residue from XYZ to ALA is a minimal perturbation that does not affect the
> overall conformational ensemble. Therefore, a reasonable approximation is
> to use the trajectory you generated in step 1 in place of the trajectory
> you generated in step 2. You still need a topology file of the alanine
> mutant, but once you have that, you can feed MMPBSA.py the mutated complex
> and receptor files (or complex and ligand files if the mutation is in the
> ligand), after which MMPBSA.py will automatically figure out which residue
> has been mutated, then generate a matching trajectory file in which the
> 'new' alanine is in exactly the same conformation as the original residue.
>
> This procedure eliminates the (long) MD step in your step #2. See the
> MMPBSA.py paper for some more details on the implementation and method.
>
> HTH,
> Jason
>
> On Mon, Dec 17, 2012 at 5:01 PM, Jonathan Gough
> <jonathan.d.gough.gmail.com>wrote:
>
> > Dear Guru's,
> >
> > I'm not sure I completely understand the alanine scanning
> > experiment/algorithm in MMPBSA.py and if anyone can set me straight, that
> > would be AWESOME.
> >
> > Here is what I THOUGHT i needed to do.
> >
> > 1. create a system of 2 proteins. save prmtop and inpcrd for unsolvated
> > complex and individual proteins.
> > - solvate, minimize, heat, density, equilibrate, and then do a production
> > run to get snapshots. (MMPBSA calculations can be done on this alone
> > obviously)
> >
> > 2. mutate 1 residue from one protein. save prmtop and inpcrd for
> > unsolvated complex and individual proteins.
> > - solvate, minimize, heat, density, equilibrate, and then do a production
> > run to get snapshots. (MMPBSA calculations can be done on the mutant
> alone
> > obviously)
> >
> > 3. Run MMPBSA using both sets of MD snapshots to find the difference
> > between the 2.
> >
> >
> > in re-reading I am getting the impression that I didn't really need to do
> > step 2. Is that correct?
> > Sorry if this is basic - I think i have just confused myself...
> >
> > Can I compare the energy between the 2 different MD runs directly? or
> > would I be missing something if I did?
> >
> > Thanks,
> > JOnathan
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> >
>
>
>
> --
> Jason M. Swails
> Quantum Theory Project,
> University of Florida
> Ph.D. Candidate
> 352-392-4032
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Received on Mon Dec 17 2012 - 17:30:04 PST
