Team:TU Darmstadt/Project/Bio/Modeling/sec1
Computational Design of Riboswitches
Abstract
Even usage of already proposed riboswitches in individual projects often require to change nucleobases in RNA or DNA sequences without altering the structure formed by the original sequence. However, minor base interchanges in the sequence may result in completely different structures that would render the intended riboswitch unusable. We used state-of-the-art computational structure prediction algorithms to implement routines that automate the process of base pair interchanges, but preserve the original structure to ensure functionality of the riboswitch. Furthermore, we were able to develop a genetic algorithm that is able to completely design a new riboswitch. Those algorithms are provided in form of a webservice and may be used freely by the community.
Introduction
Biomolecular structure prediction is an essential part in the research of many biological and chemical areas. In the case of riboswitch design, we are especially intereseted in the RNA structure prediction problem. Due to the high conservation of base-pairings in RNA or DNA sequences, most computational methods for this problem direct their efforts to predicting the secondary structure of such sequences.
Goal
Our goal within this subproject is to use secondary structure prediction algorithms of RNA sequences to autonomously search for optimal base pair interchanges that preserve a specific secondary structure or obey conditions on the structure. Regarding riboswitches in particular, we would like to develop programs that can computationally design cis-repressing RNA sequences (crRNAs) that lock specific regions of the sequence and transacting RNA sequences (taRNAs) that unlock them again. Resulting riboswitches may be used by our safety group in the iGEM 2015 project and support the synthetic biology community by facilitating the handcrafted design of such riboswitches.