On Thu, Mar 21, 2013 at 3:05 PM, Amy Davenport <adavenpo.ucsd.edu> wrote:
> > Hi all,
> > I'm hoping someone can help me figure out how to calculate the mmgb dc
> > energies for the interface between two subunits in a large complex. I
> have
> > done this type of calculation before, for a single protein that has been
> > cut to form the ligand and receptor with little problem.
> >
>
> When you say 'cut', you mean what you call the 'receptor' and 'ligand' are
> covalently bound?
>
> Yes, I retain all of the atoms of the full protein, but break one peptide
> bond to form a ligand and receptor.
>
This is dangerous, and not at all something that MM/PBSA is designed to
handle. Note that tleap will automatically convert chain-ending residues
into C- or N-terminal residues, so the number of atoms will not match up.
Even if you 'successfully' generate topologies/coordinate files, you will
get a warning about bonded terms not being consistent, and you will have to
interpret your results (and defend what you did) to account for the effects
of dangling bonds and unfilled valences.
> > This time, the overall complex is made up of two identical proteins (in
> > sequence, not position). I have designated one of them the ligand and one
> > the receptor for the purposes of this calculation. Both DC and non
> > decomposed free energy calculations work well for one of the two
> proteins,
> > and for some reason fail for the second. I have tried switching the
> ligand
> > and receptor definitions, and it still fails for the second, regardless
> of
> > which it is.
> >
>
> You need to be more specific. We have no way of knowing what "failed"
> means -- different 'failures' are indicative of different problems. Did
> the calculation die with an error message? (If so, we need to know exactly
> how you got the error and what that error message is). Do you just get
> ridiculous numbers? Do you get a warning? Etc.
>
> Sorry to be vague. For calculation of the MM-GB or PBSA energies, I get
> ridiculous numbers. But they only come from one of the two subunits (the
> one I set as the ligand).
>
> For calculation of decomposed energies (which I do with GB, as I am using
> Amber 10),
If you are using Amber 10, you will need to use mm_pbsa.pl to perform
decomposition analysis, since MMPBSA.py requires Amber 11 or greater for
decomposition calculations.
> the problem I run into is that random residues return values of
> **********. So they fail because they are missing numbers for particular
> residues. For example, I get
> TDC 573 22914.777 ********* 12.994 -160.534 90.979
>
> I have run into a similar problem before, but it had always been giving
> errors for the same residue in each snapshot.
> TDC 573 22611.434 46476.477 30.092 -160.260 99.821
> As you can see, this isn't the case here, as that is data from the same
> residue, but a different snapshot. I don't know why this is happening, and
> structurally I see nothing wrong with the residues.
>
The issue here is that the numbers are too large. There are lots of
reasons this could happen (especially if you are cutting covalent bonds).
If you are using MMPBSA.py, this is likely to occur after the first frame
is analyzed, since energies are accumulated rather than reset for each
subsequent snapshot.
HTH,
Jason
--
Jason M. Swails
Quantum Theory Project,
University of Florida
Ph.D. Candidate
352-392-4032
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Received on Thu Mar 21 2013 - 16:00:02 PDT
