title: Computational design of allosteric ribozymes as molecular biosensors.
abstract: Nucleic acids have proven to be a very suitable medium for engineering various nanostructures and devices. While synthetic DNAs are commonly used for self-assembly of nanostructures and devices in vitro, functional RNAs, such as ribozymes, are employed both in vitro and in vivo. Allosteric ribozymes have applications in molecular computing, biosensoring, high-throughput screening arrays, exogenous control of gene expression, and others. They switch on and off their catalytic function as a result of a conformational change induced by ligand binding. Designer ribozymes are engineered to respond to different effectors by in vitro selection, rational and computational design methods. Here, I present diverse computational methods for designing allosteric ribozymes with various logic functions that sense oligonucleotides or small molecules. These methods yield the desired ribozyme sequences within minutes in contrast to the in vitro selection methods, which require weeks. Methods for synthesis and biochemical testing of ribozymes are also discussed.
authors.affiliation: Sofia University "St. Kliment Ohridski", 8 Dragan Tzankov Blvd., 1164 Sofia, Bulgaria. Electronic address: robert.penchovsky@hotmail.com.
authors.forename: Robert
authors.initials: R
authors.lastname: Penchovsky
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D001483:Base Sequence; D015374:Biosensing Techniques; D019295:Computational Biology / Q000379:methods*; D006801:Humans; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000378:metabolism; D016337:RNA, Catalytic / Q000737:chemistry / Q000378:metabolism*
chemical_list: D009841:Oligonucleotides; D016337:RNA, Catalytic
keywords: Allosteric ribozymes; Computational design; Hammerhead ribozymes; High-speed allosteric ribozymes; Molecular biosensors; Nucleic acid engineering; Oligonucleotide-sensing ribozymes; RNA length-sensing ribozymes; RNA-based computing; Small molecule-sensing ribozymes