AMBER Archive (2003)

Subject: RE: Valdiation of Latest Amber parameters

From: Yong Duan (yduan_at_udel.edu)
Date: Mon Jul 07 2003 - 18:28:41 CDT

Dear Sie Meshkat:

As David pointed out in his reply, there is no systematic test on these
peptides as far as the comparison with the Beachy et al energies is
concerned.

I would probably suggest you think a little differently when you use QM
data as the basis for comparison.

Let us not forget that the Beachy et al energies (and conformations)
were calculated in gas-phase. In my opinion, it is almost irrelevent as
far as these energies are concerned. So, please do not treat them as
something written by a mysterious force (e.g., God or Buhda or someone
in that capacity). It is probably more approperiate to treat them as a
MISGUIDED attempt to compare force fields that are designed to mimick
condensed-phase energies. The later is just simply too different from
the gas-phase energies. It is misleading to mix these two things.
Although it sounds too extreme (it probably is), I will go a step
further to suggest those who did the comparison either did not
understand the basics of electronic strucutres or intentionally mislead
readers.

Besides, half of the 10 conformers in the Beachy et al studies contains
the left-handed-alpha-helical conformation. For small peptides (in
gas-phase), this could be very important. This, of course, assumes that
you (or majority of our user community) is interested in studying
gas-phase behavior of small peptides. As far as I know, (I can be
wrong), almost none of the users do it. For large peptide or proteins,
these are almost irrelevant since the region is rarely sampled in
experiments. So, disaggreement in this area does not really mean much.

A more interesting and relevant comparison is the energies in the beta-
and helical- regions. Even that, gas-phase energies are just gas-phase
energies.

Sorry if I sound too deffensive (and perhaps too edgy, which is the
effect of a bottle of wine). Although I did not do the work, I thought
it is quite important to clear up some of the misunderstandings, in
large part, due to the work by Beachy et al. I hope I am not alone. In
short, I suggest dismiss the comparison. If we are serious, we almost
have to do better QM calculations in which solvation effect is properly
taken into account. Then, we will see just how much off we are from the
mark.

Yong
*************
PS: These are just my personal 2-cents. Have nothing to do with AMBER or
people who developed AMBER and its force field.
************
-----Original Message-----
From: David A. Case [mailto:case_at_scripps.edu]
Sent: Monday, July 07, 2003 5:24 PM
To: Sia Meshkat
Cc: amber_at_heimdal.compchem.ucsf.edu
Subject: Re: Valdiation of Latest Amber parameters

On Mon, Jul 07, 2003, Sia Meshkat wrote:

> Are there any papers or data available on the results of the latest
> Amber parameters for simple peptides?

Not as far as I am aware.

>
> I have attached two conformations of Alanine Tetrapeptide from the
> frequently cited Beechy et al paper in JACS 1997-119.
>
> In the following experiment, I minimized the potential energy of these
> two conformations using the parm99.dat parameters + 2002 charges
> (all_amino02.in). As a result of energy minimization, both
> conformations converge to a single conformation. In earlier Amber
> parameter sets, such as ff94, these two conformations remain distinct,
> when minimized.

Just to be sure: you should only use the above parameters with
polarization
turned on. But (to repeat the above) there has not yet been a lot of
testing
of ff02. My best guess would be that ff02EP is likely to be better than
ff02,
but that both will continue to have some of the phi-psi problems that
have
been noticed for other force fields that use parm94.dat or parm99.dat.
But this is a "guess", not an observation.

..dac 

-- 

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