QSAR - sensitivity to atomic charge models?

QSAR Society,

        I am looking for literature publications, white papers, or other
presentations which show that using
various charge models for small molecules can result in dramatically
different QSAR descriptor-based models.

        I was quite surprised recently to observe that two classification
trees built using the same descriptor, but
calculated using two different charge models had very different R2 values
for the same training set. If I had used only
the first set of charges, I would have concluded that the descriptor does
not fit the data well ! However, using the
second set of charges, I conclude that the descriptor does fit the data
reasonably well. Crossvalidation shows that the
model constructed using the second set of charges is OK. However, why
should I believe that my second set of charges is
"optimal" ?

        Hence, how much effort do you make testing the sensitivity of your
descriptors and resulting models to various
methods of computing atomic charges - Gasteiger-Huckel, MNDO, AM1, etc.

        I would appreciate any thoughts and comments on this issue.

        Regards,
        Jim Metz

James T. Metz, Ph.D.
Research Investigator Chemist

GPRD R46Y AP10-2
Abbott Laboratories
100 Abbott Park Road
Abbott Park, IL 60064-6100
U.S.A.

Office (847) 936 - 0441
FAX (847) 935 - 0548

james.metz]|[abbott.com

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Received on 2004-06-08 - 21:34 GMT