RNAiFold2T: Constraint Programming design of thermo-IRES switches

• DOI: 10.1093/bioinformatics/btw265
• Publication Date: 2016-06-15T15:43:52Z
• Authors: Juan Antonio Garc...; Ivan Dotu; Javier Fernandez-...; Gloria Lozano; Jorge Ramajo; Encarnacion Marti...; Peter Clote
• Keywords: Folding (DSP implementation)

Abstract Motivation: RNA thermometers (RNATs) are cis -regulatory elements that change secondary structure upon temperature shift. Often involved in the regulation of heat shock, cold shock and virulence genes, RNATs constitute an interesting potential resource synthetic biology, where engineered could prove to be useful tools biosensors conditional gene regulation. Results: Solving 2-temperature inverse folding problem is critical for RNAT engineering. Here we introduce RNAiFold2T, first Constraint Programming (CP) Large Neighborhood Search (LNS) algorithms solve this problem. Benchmarking tests RNAiFold2T against existent programs (adaptive walk genetic algorithm) show our software generates two orders magnitude more solutions, thus allowing ample exploration space solutions. Subsequently, solutions can prioritized by computing various measures, including probability target ensemble, melting temperature, etc. Using strategy, rationally designed thermosensor internal ribosome entry site ( thermo -IRES) elements, whose normalized cap-independent translation efficiency approximately 50% greater at 42 °C than 30 °C, when tested reticulocyte lysates. Translation lower wild-type IRES element, which on other hand fully resistant shift-up. This appears purely computational design functional thermoswitches, certainly thermo-IRES elements. Availability: publicly available as part new release RNAiFold3.0 https://github.com/clotelab/RNAiFold http://bioinformatics.bc.edu/clotelab/RNAiFold , latter has a web server well. The written C ++ uses OR-Tools CP search engine. Contact: [e-mail] Supplementary information: data Bioinformatics online.