Department of Genetics, Faculty of Biology, Sofia University "St. Kliment Ohridski", 8 Dragan Tzankov Boulevard, 1164 Sofia, Bulgaria. robert.penchovsky@hotmail.com
Biomacromolecules 2013 Apr 8Here I describe accurate and time-efficient computational methods for designing small molecule-sensing allosteric ribozymes that serve as logic gates with NOT or YES Boolean logic functions. Theophylline-sensing ribozymes are engineered to have a high cleavage rate of 1.3 min(-1) under physiologically relevant conditions. They are highly specific to theophylline and do not respond to caffeine, which differs in a single methyl group. These ribozymes are designed by fusing a theophylline aptamer with an extended version of the hammerhead ribozyme by modeling secondary structures. Purine-sensing ribozymes are designed by fusing the minimal version of the hammerhead ribozyme with bacterial guanine or adenine aptamers by modeling 3D interactions. I have developed high-throughput compatible arrays based on purine RNA sensors that can be used for antibacterial drug discovery. The ribozymes can be employed as molecular sensors in various applications, including exogenous control of gene expression, high-throughput screening arrays, and molecular computing.
Robert Penchovsky. Computational design and biosensor applications of small molecule-sensing allosteric ribozymes. Biomacromolecules. 2013 Apr 8;14(4):1240-9
PMID: 23452219
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