Designing a New Diels鈥揂lderase: A Combinatorial, Semirational Approach Including Dynamic Optimization.

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• 作者：Mats Linder ; Adam Johannes Johansson ; Tjelvar S. G. Olsson ; John Liebeschuetz ; Tore Brinck
• 刊名：Journal of Chemical Information and Modeling
• 出版年：2011
• 出版时间：August 22, 2011
• 年：2011
• 卷：51
• 期：8
• 页码：1906-1917
• 全文大小：1196K
• 年卷期：v.51,no.8(August 22, 2011)
• ISSN：1549-960X

文摘

A computationally inexpensive design strategy involving 鈥榮emirational鈥?screening for enzymatic catalysis is presented. The protocol is based on well-established computational methods and represents a holistic approach to the catalytic process. The model reaction studied here is the Diels鈥揂lder, for which a successful computational design has recently been published (Siegel, J. B. et al. Science2010, 329, 309鈥?13). While it is a leap forward in the field of computational design, the focus on designing only a small fraction of the active site gives little control over dynamics. Our approach explicitly incorporates mutagenesis and the analysis of binding events and transition states, and a promising enzyme鈥搒ubstrate candidate is generated with relatively little effort. We estimate catalytic rate accelerations of up to 10⁵.