Subject: Re: CCL:when to take a logarithm of biological activity in QSAR studies?

From: Andreas Klamt <klamt{at}cosmologic.de>
Date: Tue, 30 Dec 2003 14:40:03 +0100

Jaroslaw,

since in physical and biological chemistry we are almost always dealing 
with "activities" which are portions of compounds being in one state and 
other portions being in another state, and since the distribution 
between such states is governed by Boltzmann factors, it is most useful 
to convert the partition quantities to free energy quantities by taking 
the logarithm. All of our molecular QSAR descriptors are much more 
likely to be linearly related to the free energies than to the original 
partition properties.

For the same reason I also recommend to convert biological activities as 
binding percentages or percentage of intestinal absorption into 
logarithmic partition properties. But care has to be taken since you 
have to do it in the following way:

Let PA be the percentage being in the specified state A. Then we have a 
percentage

PnonA = 100 - PA

not being in state A and the logarithmic distribution between state A 
and nonA is

log(PA/(100-PA))

Furthermore, typically data measured or collected on a percentage scale 
are quite crude at the ends, i.e. close to 0 and 100, while the 
logarithmic scale is quite sensitive there. So you should exclude 
measurements too close to 0 or 100 from the QSAR regression and may 
finally confirm whether you generated model correctly predicts the 
activities of the respective compounds close eneough to 0 or 100.

Regards

Andreas

Jaroslaw Panek wrote:

>Dear CCLers,
>
>there is an established tradition of taking a LOGARITHM of concentrations
>(e.g. -log (IC50), -log(ED50) ) as biological activity parameter in QSAR
>studies. As I understand, this comes either from the need to bring widely
>different numerical data (like 0.0001 and 0.1) into more balanced scale,
>or from generally logarithmic nature of biological response to external
>stimuli. Now, my question is: do you think that when applying other,
>non-concetration-based types of biological activity, one should also take
>their logarithm for QSAR studies? I am thinking specifically about
>percentages, as in "inhibition percentage", which are commonly encountered
>as results of biological assays.
>
>Happy New Year to everybody!
>
>Jaroslaw Panek
>Faculty of Chemistry, University of Wroclaw
>ul. F. Joliot-Curie 14, 50-383 Wroclaw, Poland
>
>
>
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