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



 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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