Evolutionary computational methods to predict oral bioavailability QSPRs.
This review discusses evolutionary and adaptive methods for predicting oral bioavailability (OB) from chemical structure. Genetic Programming (GP), a specific form of evolutionary computing, is compared with some other advanced computational methods for OB prediction. The results show that classifying drugs into 'high' and 'low' OB classes on the basis of their structure alone is solvable, and initial models are already producing output that would be useful for pharmaceutical research. The results also suggest that quantitative prediction of OB will be tractable. Critical aspects of the solution will involve the use of techniques that can: (i) handle problems with a very large number of variables (high dimensionality); (ii) cope with 'noisy' data; and (iii) implement binary choices to sub-classify molecules with behavior that are qualitatively different. Detailed quantitative predictions will emerge from more refined models that are hybrids derived from mechanistic models of the biology of oral absorption and the power of advanced computing techniques to predict the behavior of the components of those models in silico.
Bains
William
W
Amedis Pharmaceuticals, Unit 209, Cambridge Science Park, Milton Road, Cambridge, CB4 OGZ, UK. william.bains@amedis-pharma.com
Gilbert
Richard
R
Sviridenko
Lilya
L
Gascon
Jose-Miguel
JM
Scoffin
Robert
R
Birchall
Kris
K
Harvey
Inman
I
Caldwell
John
J
D000818:Animals; D001185:Artificial Intelligence; D001682:Biological Availability; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D008956:Models, Chemical; D011237:Predictive Value of Tests; D012984:Software