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Image Annotation and Database Mining to Create a Novel Screen for the Chemotype-Dependent Crystallization of HCV NS3 Protease

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journal contribution
posted on 06.04.2011, 00:00 authored by Herbert E. Klei, Kevin Kish, Mark F. Russo, Steve J. Michalczyk, Matthew H. Cahn, Jeffrey Tredup, ChiehYing Chang, Javed Khan, Eric T. Baldwin
An effective 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 crystallization database enables the creation of custom crystallization screening strategies. Because of the strong chemotype-dependent crystallization observed with HCV NS3 protease (HCVPr), this strategy was applied to a chemotype resistant to all prior crystallization efforts. The crystallization database was mined for ingredients used to generate earlier HCVPr/inhibitor co-crystals. A random screen was created from the most prolific ingredients. A previously untested combination of proven ingredients was identified that led to a successful crystallization condition for the resistant chemotype.