Comparison of the inhibition of Escherichia coli and Lactobacillus casei dihydrofolate reductase by 2,4-diamino-5-(substituted-benzyl)pyrimidines: quantitative structure-activity relationships, x-ray crystallography, and computer graphics in structure-activity analysis
- 1 July 1982
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 25 (7), 777-784
- https://doi.org/10.1021/jm00349a003
Abstract
The inhibition constants (Ki app) obtained from the action of 44 2,4-diamino-5-(substituted-benzyl)pyrimidines on dihydrofolate reductase (DHFR) from E. coli and L. casei are used to derive quantitative structure-activity relationships (QSAR). These equations bring out a number of differences in the DHFR which can be understood at the atomic level by studying color stereo computer graphics models constructed from the X-ray coordinates of the enzyme-inhibitor complexes. The combination of QSAR and X-ray crystallography interpreted via high-performance computer graphics offers a new level of sophistication to extend understanding of enzyme-ligand interactions, which, when the crystallography is known, opens up a more scientific approach to drug development.This publication has 13 references indexed in Scilit:
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