Subject: RE: summary on adding charges to thousands of molecule via MOPAC

From: Stephen Bowlus <[email-masked]>
Date: Mon, 22 Jul 2002 08:12:04 -0700

Charges from Huckel and extended Huckel theory rely only on the connectivity
of the system.  To the extent that Gasteiger charges (and its several
variants) are elaborations of Huckel theory, I would expect these would give
reliable charges, within the framework of that theory.  In fact, adding
Gasteiger-Huckel charges to a 2D molecule (MDL sdf files) before optimizing
the molecule in Sybyl (using a force field, which captures the connectivity
information) is a fairly common task in our lab.  You can do these
calculations in Alchemy (cheap) or VEGA (free!).  You might also check
TINKER (as a free/cheapware), but I am not experienced in its use. 

Doing 1SCF in MOPAC on a 2D molecule will give you meaningless charges (not
just inaccurate!).  This is because MOPAC's (NDO) methods do not depend on
the "bonding" information implied by a connection table - bonding is
inferred after a stable (optimized) configuration of the nuclei in the
electron soup is calculated.  The charges will be calculated (you can always
do the calculation!) but the 2D molecule is so far from a stable
configuration that heaven alone knows what they will mean. 

"Inflating" a 2D molecule to 3D in MOPAC _may_ work, but again, since
bonding is inferred after optimization, there is a good chance that your
structures will be ... ummm, novel?  This is particularly true if you start
with Cartesian coordinates.  With the Z-matrix (internal coordinates) ...
maybe yes, maybe not.  I've had some wonderful experiences with poorly
defined (in 3-space) starting structures giving very strange molecules after
optimization when I drew in the lines representing what I thought were
bonds.  At best, you will need to carefully review each structure after the
calculation. 

Hope this helps,
Steve