Subject: CoMFA

From: Christian Pilger <[email-masked]>
Date: Wed, 6 Sep 2000 11:05:06 +0200

Dear CClers,

	I generated an alignment for the compounds of my dataset which I
want to use for CoMFA. How should the grid-points be treated that are
positioned within the common volume of the aligned structures ? Many
programs simply use a maximum cutoff-value, keeping these grid points and
including them into the statistical analysis. However, wouldn't it be
more reasonable to exclude such grid points at all ?

Regards,

Christian

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From: David Turner <[email-masked]>
Date: Wed, 06 Sep 2000 15:03:57 +0200

Dear Christian

I don't think there's a right answer to this - possibly it is best
to try both and determine whether there is any information change
when using the different approaches ie as reflected in the PLS results. 
My experience is that it usually doesn't matter whether you include or 
exclude these points. Alternatively, you could try CoMSIA which has 
smoother Gaussian-based distance potentials than the Lennard-Jones 6-12
and no possibility for singularities. Also, for steric so-called "fields" 
indicator variables seem to work just as well. This is because the LJ 
potential is very small (low variance) once you move a little way from 
the vdw surface while the high variance variables, to which PLS is sensitive, 
are concentrated close to the surfaces.

David Turner

-- 
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David Turner                                             Synt:em
Senior Modeling Scientist              Parc Scientifique G.Besse
Computational Drug Discovery                         30000 Nimes
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