AMBER Archive (2007)

Subject: RE: AMBER: Gas-phase energies (and more)

From: Yong Duan (duan_at_ucdavis.edu)
Date: Thu Jan 25 2007 - 17:58:48 CST

Jason,

Actually the term "gas-phase" or "condensed phase" is somewhat relative.

Taking your system as an example, if the charges are developed using the QM
esp of the entire molecule, it is probably justified to use gas-phase esp if
the intention is to model its gas-phase behavior, assuming you use multiple
representative conformations in the esp calculation. However, if the
approach is to obtain the charges of the di-peptides and piece together the
charges for the whole molecule, it is not a clear cut as to how to obtain
the charges. The reason for this is that, as you might anticipate, the
peptide (Ace-Arg(+)-Ala-Ala-Ala-Ala-Nme) is sufficiently large that it may
have tendency to form compact (collapsed) structures, even in gas-phase. If
this is the case, the residues that tend to be burried should perhaps use
the condensed-phase charges. Intuitively, only those exposed atoms should
assume gas-phase charges and other atoms should behave like in some sort of
solvent. This is not exactly "hair-splitting". I would say that only the
fully polarizable force field can do this (or, in a more modest tone, has
the potential to do the job).

If you only want to simulate these small peptides in gas-phase, I think you
should use the ff02 charges with polarizability because, theoretically, it
should be able to deal with it. In fact, if you go through the paper of
Cieplak et al (JCC paper with Kollman and Caldwell), the charges of ff02 was
fitted in gas-phase with polarization. If you are concerned by the added
cost, simulating such small peptides is really pretty easy these days even
using the fully polarizable force field.

As for the torsion parameters, because each torsion parameter set is closely
related to the charges, it makes sense to try Wang et al's torsion
parameters first. In the work of Wang, the torsion tuning was done in
gas-phase. In other words, the fitting of the torsion was done by comparing
the di-ala gas-phase energies. But the tests were done in aqueous solution.
So, it should work.

Hope this helps.

Good luck!

yong

-----Original Message-----
From: owner-amber_at_scripps.edu [mailto:owner-amber_at_scripps.edu] On Behalf Of
Jason K
Sent: Thursday, January 25, 2007 3:04 PM
To: amber_at_scripps.edu
Subject: AMBER: Gas-phase energies (and more)

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

Jason

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?

-----------------------------------------------------------------------
The AMBER Mail Reflector
To post, send mail to amber_at_scripps.edu
To unsubscribe, send "unsubscribe amber" to majordomo_at_scripps.edu