Nonlinear quantitative structure-activity relationship for the inhibition of dihydrofolate reductase by pyrimidines.
A novel method for quantitative structure-activity relationship (QSAR) analysis is presented. The method, which does not assume any particular functional form for the QSAR, develops nonlinear relationships between parameters describing a set of molecules and the activity of the molecules. For the QSAR of the inhibition of Escherichia coli dihydrofolate reductase by 2,4-diamino-5-(substituted benzyl)pyrimidines, the method compares favorably to other nonlinear methods. Cross-validation trials demonstrate that the predictive ability is as accurate as other methods, and the method is simpler and faster than neural network and machine-learning methods. Consequently, its implementation is much easier, and interpretation of the generated QSAR is more straightforward.
Hirst
J D
JD
Department of Molecular Biology, Scripps Research Institute, La Jolla, California 92037, USA, jhirst@scripps.edu
D004926:Escherichia coli / Q000201:enzymology; D005493:Folic Acid Antagonists / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D005493:Folic Acid Antagonists