Hi AMBER users,
I'm wondering if it is theoretically possible to decompose the entropy term
from an MM PBSA/GBSA calculation to determine the contribution of each
residue?
I realize the script currently does not support this, and the manual makes
that quite clear. I also believe I understand that in taking in the whole
complex there would be no way to actually do this decomposition easily.
What I'm wondering is, from a theoretical perspective, if one did the
normal alignment of the whole complex to remove those irrelevant rotations
and translations, and then stripped out all but the residue of interest,
and performed the entropy calculations (Quasi-harmonic or nmode) on just
that reduced trajectory (which has been pre-aligned as part of the whole
complex), would you get something sensible? That is, would doing this for
each residue give a final result that more or less added up to what you
would get from doing the whole complex (I realize there is a lot of
uncertainty in entropy calculations as it is, and so there would be a
tremendous propagation of error involved)?
I'm asking about this because MM/PBSA calculations seem to offer a very
nice advantage over other methods for determining say ligand binding energy
(umbrella sampling, thermodynamic integration etc..) in that one can get
these per residue decompositions of the energy terms, and thereby get a
clue as to how the protein for instance, might be re-engineered for better
binding, whereas methods like umbrella sampling would essentially require a
guess, followed by another whole analysis of the mutated complex in order
to test only one potential mutation.
Thanks,
~Aron
--
Aron Broom M.Sc
PhD Student
Department of Chemistry
University of Waterloo
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Received on Sat Feb 16 2013 - 10:30:02 PST
