Re: QSAR - sensitivity to atomic charge models?

I suggest that you have a look into my review paper in Current
Pharmaceutical Design, 2003, 9, 1575-1606, in which this and other
related questions are discussed in a more sophisticated model.
Isaac Bersuker

james.metz~!~abbott.com wrote:

>
> 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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-- 
Dr. Isaac B. Bersuker
Institute for Theoretical Chemistry
The University of Texas at Austin
Chem & Biochem Department
1 University Station A5300
Austin, TX 78712-0165
Phone: (512) 471-4671; Fax: (512) 471-8696
E-mail: bersuker^mail.cm.utexas.edu
http://ne060.cm.utexas.edu/~bersuker