With the recent competitiveness of GPUs (graphical processing units) compared to CPUs in terms of scientific computation researchers have been able to conduct more extensive Molecular Dynamics research in terms of both simulation length and system size. In this study we observe the effect of 150 millimolar ammonium chloride on the dynamics of Helicobacter pylori (HP) urease, a 308,741 atom system over 500 nanoseconds. HP urease is an enzyme that hydrolyzes urea to form ammonium and carbamate, which in turn help to regulate the pH of the bacteria’s immediate environment, enabling the survival of HP in the harshly acidic stomach. Inhibitors of HP urease prevent the acid defense mechanism from occurring and thus will prevent the survival of these bacterial colonies in humans. This lengthy simulation allowed us to carefully monitor the interaction of NH4+ ions with the protein. Of particular interest was the interaction of ammonium ions near a deprotonated lysine residue near both the postulated active site exit flap from our previous work and the ovoid openings leading to the interior of the protein. The proximity of ammonium ions to the deptrotonated lysine side chain provides a possible proton transfer mechanism allowing the departing ammonium to convert to ammonia, an excellent base for neutralization of acid in the H. pylori immediate vicinity. Two deptrotonated lysine residues reside on opposite sides of the ovoid openings with a sweeping motion spanning over half of the opening’s longer diameter. If the deprotonated lysine residue indeed facilitates the conversion of hydrolysis products into ammonia a potential product line target for enzyme inhibition exists.

Interaction of aqueous ammonium chloride with Helicobacter pylori urease

249th National Meeting (2015)

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