Re: QSAR - sensitivity to atomic charge models?

James,

I have run numerous 3D QSAR models using numerous charge
calculations, and the results are equivocal...ie, the resulting
models have equivalent predictive strengths. What this says
about the charge calculation may be nothing, since what is
important in a 3D QSAR model is consistency, more so than truth.

-Arthur

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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Received on 2004-06-09 - 12:09 GMT