Most organisms use ATP for substrate level phosphorylations during glycolysis; however, it is recognized that the parasitic protists lacking mitochondria have glycolytic enzymes that utilize inorganic pyrophosphate(PPi) as the high energy phosphate donor instead of ATP. PPi-phosphofructokinase (PPi-PFK) is the rate limiting glycolytic enzyme found in Entamoeba histolytica, Giardia lamblia, Toxoplasma gondii, Trichomonas vaginalis, and Naegleria fowleri, and as such represents an important drug target. Current therapy for these infections is not ideal, especially for pregnant women and children, and newer more selective agents would be welcome.

Using the PPi-PFK amino acid sequence from E. histolytica, a model has been constructed based on the three dimensional structure of the ATP-PFK from Bacillus stearothermophilus. This model was constructed using the computer program Look (Molecular Applications Group, Palo Alto, CA), and has been validated using several computational strategies including comparison with a backbone dependent rotamer library for analysis of side chain orientation.

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