Yong makes a lot of very good points here.
I would add, though, that if we had a good model
for polarization, one could make the argument that
fitting the gas-phase data would be a good goal.
Then all solvent effects on charges could be included
in the polarization. However, as Yong points out,
it is in appropriate to use partial charges designed
for aqueous solution to reproduce gas-phase QM
relative energies. Whether one should be able
to reproduce the actual minima (not the energies)
is less clear.
Carlos
===================================================================
Carlos L. Simmerling, Ph.D.
Assistant Professor Phone: (631) 632-1336
Center for Structural Biology Fax: (631) 632-1555
Stony Brook University Web: http://comp.chem.sunysb.edu/carlos
Stony Brook, NY 11794-5115 E-mail: carlos.simmerling.stonybrook.edu
===================================================================
----- Original Message -----
From: "Yong Duan" <yduan.udel.edu>
To: <amber.heimdal.compchem.ucsf.edu>; "'Sia Meshkat'"
<sMeshkat.proteinmechanics.com>
Sent: Monday, July 07, 2003 7:28 PM
Subject: RE: Valdiation of Latest Amber parameters
>
> 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.scripps.edu]
> Sent: Monday, July 07, 2003 5:24 PM
> To: Sia Meshkat
> Cc: amber.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
>
> --
>
> ==================================================================
> David A. Case | e-mail: case.scripps.edu
> Dept. of Molecular Biology, TPC15 | fax: +1-858-784-8896
> The Scripps Research Institute | phone: +1-858-784-9768
> 10550 N. Torrey Pines Rd. | home page:
> La Jolla CA 92037 USA | http://www.scripps.edu/case
> ==================================================================
>
>
>
Received on Tue Jul 08 2003 - 01:53:01 PDT
