Computational Modeling of Cruzain Inhibitors

The HQSAR, AutoQSAR, CoMFA, and CoMSIA models were built as previously described [21 (link),22 (link),23 (link),24 (link)] using SYBYL-X 2.1 (Certara Inc., Princeton, NJ, USA) and Maestro (release 2016-3) (Schrӧdinger LLC, New York, NY, USA). The 3D structures of the compounds were built using Epik at pH 5.5 and minimized using LigPrep and OPLS3 (Schrӧdinger LLC, New York, NY, USA) [25 (link),26 (link),27 (link)]. The X-ray structure of cruzain deposited in the Protein Data Bank (PDB 3KKU, 1.28 Å) [28 (link)] and GOLD 5.3 (Cambridge Crystallographic Data Centre, Cambridge, UK) [29 (link)] were used in the molecular docking studies. The enzyme-inhibitor complexes were visualized using Maestro (release 2016-3) and Chimera (University of California, San Francisco, CA, USA) [30 (link)].