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Dihydrofolate Reductase (DHFR) is an enzyme important for the process of cell growth in organisms. Thus, an inhibitor for DHFR can be useful to reduce the rate of cell growth. Methotrexate is such an inhibitor and is used as an anticancer drug in chemo therapy [S88]. Dihydrofolate is the natural ligand of DHFR.
The structure of both complexes of DHFR and Methotrexate and of DHFR and Dihydrofolate has been determined by X-ray crystallography. The relative orientation and conformation of Dihydrofolate and Methotrexate in the binding pocket of DHFR is a prominent example for the fact that, by no means, can the correct superposition be found by simply considering the binding skeleton or sterical aspects of the ligands alone but is heavily determined by the possible intermolecular interactions that the molecules are capable of. FlexS is able to reproduce the relative orientation and conformation of this Ligands with 0.8 A RMS (see picture) within seven minutes on a workstation, considering the full flexibility of the test-ligand Methotrexate.
Results: JMC ('98) 
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