Network análisis in complex protein-inhibitor systems : a Cruzain case study

Abstract

Chagas disease is a neglected tropical disease caused by Trypanosoma cruzi. Cruzain (Cz),the parasite major cysteine-protease, is a viable target for developing new drugs. A survey on public databases with activty activity annotations revealed that several Cz inhibitors containing a halogen a halogen atom (LX, X = CL, Br, I) were up to thousands of times more active than their non-halogenated analogs (LH) giving rise to an activity cliff in the Cz/inhibitor interaction landscape.