Subject: Re: CCL:G:Fitting point charges to ESP with Spartan

From: [email-masked] (Michelle M Francl)
Date: Mon, 4 Nov 1996 13:23:02 -0500

Wayne Huang notes:

>As there is discrepancy on resulting charges from G9x and Spartan, that
>would not be surprising. Although based on the same idea, the implementation
>could be different. It is somewhat arbitrary in at least two ways, the
>number of grid points chosen and the how far the region included. In plain
>English, it basically paints a layer of grease on the vdw surface. Too far
>beyond the vdw surface would get the charges too small (eventually approach
>zero). The extent of the exclusion of the inner volume will also affect the
>outcome (too close to the centers results in charges being too large). I would
>tend to believe the two implementations should differ by a factor, may or may
>not be linearly scalable.
>

As a clarification, most of these algorithms do not "paint a layer of
grease" onthe VDW surface, but take some collection of points outside the
VDW.  This collection is sometimes a shell around the molecules, othertimes
a box.  The size of the box is generally much larger than the molecule. 
Points within
the VDW are excluded.  The implementation of CHELP in Spartan may be
different, I know that the algorithm was recoded for Spartan based on the
original CHELP paper.

I would tend to believe the last comment regarding the relationship of the
magnitude of the charges to the selection of the surface is not correct. 
For example, when points within 2.0 x the VDW surface are excluded in
phenol, the charge on oxygen is 0.95, when points withing 0.75 of the VDW
are excluded (more points now selected closer to the atomic centers), the
charge actually _drops_ to 0.23.

As Konrad Hinsen notes:  this type of fitting is VERY unstable, and charges
should be used with great care.  More discussion can be found in our paper
which uses the singular value decomposition or SVD to examine the problem
(the paper I think Hinsen is refering to in his last post:  J.Comp. Chem.,
Francl, Carey, Chirlian and Gange, v. 17 pp368-383), as well as in papers
by Stouch and Williams.  I don't disagree with Dr. Hinsen's contention  
that computational chemists, in general, have been quite naive in their use
of the linear least squares regression for this problem.  All I can say is
that I was young and foolish when we wrote the first CHELP paper in 1987
which suggested replacing the older iterative methods with a slightly more
sophisticated method.

_____________________                                   ____________________
Michelle M. Francl                                      phone:  610.526.5108
Associate Professor                                     FAX: 610.526.5086
Dept. of Chemistry                                      
Bryn Mawr College
101 N. Merion Ave.
Bryn Mawr, PA 19010
USA

Internet:  [email-masked]
WWW:  http://fieser.brynmawr.edu/~dept/chemistry.html