Designing a New Diels-Alderase: A Combinatorial, Semirational Approach Including Dynamic Optimization
2011 (English)In: JOURNAL OF CHEMICAL INFORMATION AND MODELING, ISSN 1549-9596, Vol. 51, no 8, 1906-1917 p.Article in journal (Refereed) Published
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).
Place, publisher, year, edition, pages
2011. Vol. 51, no 8, 1906-1917 p.
Chemistry, Multidisciplinary, Computer Science, Information Systems, Computer Science, Interdisciplinary Applications
IdentifiersURN: urn:nbn:se:kth:diva-39525DOI: 10.1021/ci200177dISI: 000294081800017ScopusID: 2-s2.0-80052015812OAI: oai:DiVA.org:kth-39525DiVA: diva2:441587
FunderSwedish Research Council
QC 201109162011-09-162011-09-122012-09-03Bibliographically approved