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

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• 作者：Herbert E. Klei ; Kevin Kish ; Mark F. Russo ; Steve J. Michalczyk ; Matthew H. Cahn ; Jeffrey Tredup ; ChiehYing Chang ; Javed Khan ; Eric T. Baldwin
• 刊名：Crystal Growth & Design
• 出版年：2011
• 出版时间：April 6, 2011
• 年：2011
• 卷：11
• 期：4
• 页码：1143-1151
• 全文大小：1009K
• 年卷期：v.11,no.4(April 6, 2011)
• ISSN：1528-7505

文摘

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.