AMBER: Gas-phase energies (and more)

From: Jason K <>
Date: Thu, 25 Jan 2007 23:04:16 +0000

Dear AMBER users,

Much of the research in the group where I work addresses the structures of
boimolecules in a solvent-free environment. We are trying to reproduce our
experimental results by molecular mechanical simulations and -subsequently-
the concern that most AMBER parameter sets are tuned to replicate
condensed-phase energies for small peptides becomes quite relevant. Since
the electrostatics contribute the most to the energy of the system
(especially in vacuo), also being the kind of interactions that differ the
most between the gas phase and solution, I would like to know what approach
I could adopt to generate charge assignments that are more likely to mirror
the electrostatics in the absence of solvent. So far (to partially answer my
own question) I have come across two approaches, (excluding, of course
re-parameterising the force field in the gas-phase):

1) Use the "ff02" residues but with ipol=0 (thus using the "gas phase",
"static" point-charges). [From what I have gathered, a polarisable force
field should handle the electrostatics in a vacuum, implicit or explicit
solvent, at least in theory, but I do not know to what extent this is true
for the models in AMBER or to what extent they have been tested and hence I
am unwilling to make this assumption]. I am still unsure on whether this is
indeed appropriate, what objections could one raise against using ff02
charges for gas-phase calculations?

2) "Scaling down" the HF/6-31G* charges (by e.g. a factor of 0.8) to
somewhat relieve the overestimated dipoles. I would be extremely grateful if
someone could tell me how to calculate the partial charges for residues with
non-integer charge. Has this approach been tested?

Does anyone know any other methods for a "better" representation of
gas-phase electrostatics of biomolecules?

Finally, I am bound to ask about other parameters, especially dihedrals.
Will the tortional terms in parm99.dat or even frcmod.02 (dot
somethingsomething) drive the peptide away from the "real" gas-phase minima?
I am currently running calculations on a small system
(Ace-Arg(+)-Ala-Ala-Ala-Ala-Nme) which has been addressed previously and see
which parameter set of the ones available gives "better" energies compared
with QM, or correspondence with experiment. Yet if anyone could propose me a
different testing method or a more "standard" system, please do so. (The
reason a protonated peptide is needed is that neutral peptides are not
directly observable by mass spectrometry and related techniques).

Thanks in advance


PS1. I haven't read the paper carefully yet, but in Wang et al. J. Comp.
Chem. (2006) 27(6):781-790 were both the MM and QM calculations performed in
water for the Ace-Ala-Nme dihedral scan ("figure 3") or was the QM done in
the absence of (implicit) solvation?

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Received on Sun Jan 28 2007 - 06:07:27 PST
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