In silico study of Plasmodium falciparum proteases Plasmepsin II and IV: Prediction of biological activity of newly designed inhibitors

CHED 1305

C. Badi' Abdul-Wahid, abdulwahidc@cwu.edu1, Sarah Abdul-Wahid2, Levente Fabry-Asztalos, fabryl@cwu.edu1, and Razvan Andonie2. (1) Department of Chemistry, Central Washington University, 400 East University Way, Ellensburg, WA 98926-7539, (2) Department of Computer Science, Central Washington University, 400 East University Way, Ellensburg, WA 98926
We used the modeling software Sybyl and Chimera to study P. falciparum's Plasmepsins II and IV (PM II and IV) and their inhibitors. Sybyl was used to model 146 known inhibitors of PM II and 37 known inhibitors of PM IV. Chimera was used to study the active sites of the enzymes. Sets of molecular descriptors were compiled, which were used to train a fuzzy neural network optimized by a genetic algorithm. The fuzzy IF/THEN rules relating the physico-chemical properties to biological activities were extracted and used as a screen in the design of novel inhibitors. The biological activities of the novel compounds were then predicted by the trained neural network. Our results show that the neural network predicts reasonably well for the available data sets.
 

Undergraduate Research Poster Session: Medicinal
2:00 PM-4:00 PM, Monday, March 26, 2007 Hyatt Regency Chicago -- Riverside Center, Poster

Division of Chemical Education

The 233rd ACS National Meeting, Chicago, IL, March 25-29, 2007