Article ID Journal Published Year Pages File Type
1375786 Bioorganic & Medicinal Chemistry Letters 2008 8 Pages PDF
Abstract
Molecular dynamics simulations and free energy calculations are presented, exploring previously described experimentally studied interactions of a series of 2′-fluoro-substituted dUMP/FdUMP analogues with thymidylate synthase (TS). The results show the inhibitory behaviors of 2′-F-ara-UMP, 2′,2″-diF-dUMP and 2′,5-diF-ara-UMP to be dependent upon the binding positions and orientations adopted by the molecules of these compounds in the active site of TS. The binding mode of 2′,5-diF-ara-UMP suggests a novel role of the active site residue Trp 80, stabilizing through hydrophobic stacking the binding position of the pyrimidine ring in 2′,5-diF-ara-UMP.
Related Topics
Physical Sciences and Engineering Chemistry Organic Chemistry
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