Paper Citing NAMD - Abstract
Durrant, Jacob D.; Urbaniak, Michael D.; Ferguson, Michael A. J.; McCammon, J. Andrew
Computer-Aided Identification of Trypanosoma brucei Uridine Diphosphate Galactose 4 '-Epimerase Inhibitors: Toward the Development of Novel Therapies for African Sleeping Sickness
JOURNAL OF MEDICINAL CHEMISTRY, 53:5025-5032, JUL 8 2010
Trypanosoma brucei, the causative agent of human African trypanosomiasis, affects tens of thousands of sub-Saharan Africans. As current therapeutics are inadequate due to toxic side effects, drug resistance, and limited effectiveness, novel therapies are urgently needed. UDP-galactose 4'-epimerase (TbGalE), an enzyme of the Leloir pathway of galactose metabolism, is one promising T. brucei drug target. We here use the relaxed complex scheme, an advanced computer-docking methodology that accounts for full protein flexibility, to identify inhibitors of TbGalE. An initial hit rate of 62% was obtained at 100 mu M, ultimately leading to the identification of 14 low-micromolar inhibitors. Thirteen of these inhibitors belong to a distinct series with a conserved binding motif that may prove useful in future drug design and optimization.
