AMBER Archive (2003)

Subject: Re: Valdiation of Latest Amber parameters

From: Jiri Sponer (sponer_at_ncbr.chemi.muni.cz)
Date: Wed Jul 09 2003 - 12:03:53 CDT

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

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 Jiri Sponer
Institute of Biophysics
Academy of Sciences of the Czech Republic
Kralovopolska 135
CZ-61265 Brno
Czech Republic
e-mail: sponer_at_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
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