Dear Yong:
going back to the discussion of the "validation",
I would like to make just few points (although
the discussion has moderated already).
I do not thing it is a good idea to dismiss accurate
gas phase data. Although the aqueous solution affects
the electronic structure of segments of biopolymers,
the effects are not so dramatic. Major electronic features
of the species are not changed. AMBER anyway relies
on "gas phase" HF charges. CHARMM relies on gas phase
water ... something charges, this still is a gas phase system.
What is substantially affected by solvent is the order
of various minima, primarily due to complex specific hydration and
solvent screening effetcs. These may even invert the gas phase
(free) energy trends. This however concerns primarily
the long-range electrostatic
contributions while the intrinsic electronic
properties are an order of magnitude less sensitive
to the solvent effects.
(In order to really change the electronic structure
you need to bind for example a transition metal.)
Thus the main problem to use Beachy et al for
a comparison is not the gas phase nature of the
calculations but the selection of the structures.
QM calculations of microhydrated clusters could well
be used for comparison with force fields.
It is obvious why the ff are parametrized for
condensed phase biopolymer simulations. However, in an optimal
case the ff should also be reproduce the gas phase
data and certainly should not be drastically different.
Of course, due to simplicity of the ff this often is
not possible and one needs to calibrate the force field
for biologically relevant geometries. Then, however, we
rely on the compensation of errors and that could sometimes fail.
In any case, substantial problems to reproduce
gas phase data always are a warning sign and should be
investigated.
Best wishes,
Jiri
-------------------------------------------------------
Jiri Sponer
Institute of Biophysics
Academy of Sciences of the Czech Republic
Kralovopolska 135
CZ-61265 Brno
Czech Republic
e-mail: sponer.ncbr.chemi.muni.cz
fax: 420 5412 12179
phone: 420 5415 17133
http://www.ibp.cz/labs/LSDNA/
Wellcome Trust Senior Research Fellow for Biomedical Research
--------------------------------------------------------
Received on Wed Jul 09 2003 - 18:53:01 PDT
