Image Annotation and Database Mining to Create a Novel Screen for the Chemotype-Dependent Crystallization of HCV NS3 Protease Published as part of the Crystal Growth & Design virtual special issue on the 13th International Conference on the Crystallization of Biological Macromolecules (ICCBM13)
Herbert E. Klei, Kevin Kish, Mark F. Russo, Steve J. Michalczyk, Matthew H. Cahn, Jeffrey A. Tredup, ChiehYing Y. Chang, Javed Khan, Eric T. Baldwin · 2011
An e !ective process for screening, imaging, and optimizing crystallization trials using a combination of external and internal hardware and software has been deployed. The combination of this infrastructure with a vast annotated crystal- lization database enables the creation of custom crystalliza- tion screening strategies. Because of the strong chemotype- dependent crystallization observed with HCV NS3 protease (HCVPr),thisstrategywasappliedtoachemotyperesistanttoallpriorcrystallizatione !orts.Thecrystallizationdatabasewasmined for ingredients used to generate earlier HCVPr/inhibitor co-crystals. A random screen was created from the most proli c ingredients. Apreviously untested combinationofproven ingredientswas identi edthatled toasuccessful crystallizationcondition for the resistant chemotype.