[AMBER] Help with GIST analysis

From: Sérgio Marques <smar96.gmail.com>
Date: Wed, 19 Oct 2016 17:31:59 +0200


I have one template protein and we have recently discovered several mutants
with higher stability (e.g. Glu to Ser). This stabilization could not be
predicted computationally with any energy-based method (e.g. Rosetta,
FoldX, etc.), and we are trying to explain it. After several computational
studies and experiments, everything points out to the observed
stabilization being due to the entropic effects of the solvent, since we
failed at predicting any structural stabilization.

So I have run GIST calculations on those systems in an attempt to find the
possibly different entropic contributions from the solvent, but I am facing
some difficulties in interpreting the results. I ran the GIST on 200 ns
long MD simulations and used 4 ns-spaced snapshots, with boxes of 15 A
width centered in the mutated residues. The calculations were performed on
the aligned template protein single-point mutants using exactly the same
size and coordinates of the box (so the boxes match exactly in space).

My main questions are:

- Can I compute the mutant-wild type differences of the total quantities
(dTSorient, dTStrans, Esw and Eww) obtained for the box in order to explain
the different contributions? I tried to do that but it did not provide the
results I expected. Moreover, for some systems the Eww was huge (e.g.
1.12E+06 kca/mol, while for other systems it was more reasonable, e.g. -600

- When visualizing the results, the patterns of entropy and enthalpy around
the target residues are slightly different but not very significantly. I
was expecting the paterns with a certain negative isovalue of dTStotal to
shift farther away from the mutant. How different patterns should I expect
for a mutant that has stabilization due to the entropic contribution of the

Thank you in advance for any possible help with this matter!!

Sergio Marques
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Received on Wed Oct 19 2016 - 09:00:03 PDT
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