Confirmation of usefulness of a structure construction program based on three-dimensional receptor structure for rational lead generation.
Skeletal structures very similar to those of four known inhibitors were automatically output from our computer program LEGEND, based on the three-dimensional structure of the active site of the target enzyme, dihydrofolate reductase. Besides them, the program output novel promising structures that are stable intra- and intermolecularly. This result strongly supports the usefulness of this method for rational lead generation. New lead compounds can be obtained, not relying on chance or trial and error, if appropriate structural selection and modification of the output structures are made.
Nishibata
Y
Y
Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Itai
A
A
D001665:Binding Sites; D003198:Computer Simulation; D015195:Drug Design; D004926:Escherichia coli / Q000201:enzymology; D005493:Folic Acid Antagonists; D006860:Hydrogen Bonding; D008958:Models, Molecular; D015394:Molecular Structure; D012984:Software; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry*
D005493:Folic Acid Antagonists; D013762:Tetrahydrofolate Dehydrogenase