Designing a New Diels-Alderase : A Combinatorial, Semirational Approach Including Dynamic Optimization

• A computationally inexpensive design strategy involving 'semirational' 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-Alder, for which a successful computational design has recently been published (Siegel, J. B. et al. Science 2010, 329, 309-313). 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 substrate candidate is generated with relatively little effort. We estimate catalytic rate accelerations of up to 10(5).

Ämnesord

NATURVETENSKAP  -- Kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences (hsv//eng)

Nyckelord

Chemistry

Multidisciplinary

Computer Science

Information Systems

Computer Science

Interdisciplinary Applications

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