Virtual screening for novel urease inhibitors

The enzyme urease (urea aminohydrolase) occurs in many bacteria like Helicobacter py-lori, Klebsiella aerogenes, and Bacillus pasteurii. It catalyzes the hydrolysis of urea to ammonia and carbonate. The ammonia leads to a pH increase and enables these bacteria to survive in acidic conditions (e.g. stomach). Urease is involved in many types of dis-eases like gastritis and urinary tract infections. In agriculture urease causes nitrogen-loss of urea fertilizers. Although there are known inhibitors, their use is limited due to low efficiency and side effects [1]. Aim of this study is the virtual screening for novel inhibitors as well as the improvement and testing of our screening methodology. For virtual screening we applied the docking tool FlexX [2, 3]. In an initial study, we suc-cessfully docked all known urease-ligand complexes from the Protein Data Bank (Figure 1). Figure 1: Acetohydroxamic acid docked into H. pylori urease. The rank 1 docking result is shown in red and the reference structure (PDB code 1e9y) in yellow. About 2.5 million screening compounds were loaded from SDF files, preprocessed, and screened fully-automatically with a parallel version of FlexX. For preprocessing, Flex