Subject: COSMO vs. the water box

From: "Hr. Dr. S. Shapiro" <[email-masked]>
Date: Fri, 24 Apr 1998 11:47:05 +0200

Dear Colleagues;

	I have recently gained access to CambridgeSoft's programme "Chem3D", and
have been experimenting with one of its modules, MOPAC97.  Towards this
end, I have attempted the energy minimisation of a "semi-optimised"
structure of chloramphenicol using the PM3 Hamiltonian with COSMO (EPS =
78.4, NSPA = 60).  However, no matter what combination of keywords I try, I
cannot get gnorm < 1.9.  I read in the MOPAC93 manual that gnorm for a
COSMO calculation may not go below 1% of the value of the "dielectric
energy"; I'm not sure what Dr. Stewart means by "dielectric energy".

	My questions are as follows:

(a)  Does "dielectric energy" = dielectric constant?  If not, what _is_ the
dielectric energy?

(b)  What is it about COSMO that usually precludes gnorm going below ca. 1%
of the "dielectric energy"?

(c)  What would be the "quality" of a COSMO-miminised structure for which
the terminal gnorm value is ca. 1.9?

(d)  Generally speaking, how does the quality of a COSMO-mimimised
aqueous-solvated structure compare to the same structure minimised using
molecular mechanical techniques when that structure is embedded in a water
box?

(d)  I am given to understand that the Miertus-Scirocco-Tomasi solvation
model works best with the AM1 Hamiltonian.  I would appreciate hearing from
person who have had the opportunity to compare results of energy
minimisations of aqeuous-solvated molecules using the AM1 Hamiltonian + MST
and AM1 + COSMO, particularly with respect to the quality of the final
structures obtained.

Thanks in advance to all responders,

S. Shapiro
[email-masked]