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An Adaptive Defect Weighted Sampling Algorithm to Design Pseudoknotted RNA Secondary Structures


An Adaptive Defect Weighted Sampling Algorithm to Design Pseudoknotted RNA Secondary Structures

Zandi, Kasra, Butler, Greg and Kharma, Nawwaf (2016) An Adaptive Defect Weighted Sampling Algorithm to Design Pseudoknotted RNA Secondary Structures. Frontiers in Genetics, 7 . p. 129. ISSN 1664-8021

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Official URL: http://dx.doi.org/10.3389/fgene.2016.00129


Computational design of RNA sequences that fold into targeted secondary structures has many applications in biomedicine, nanotechnology and synthetic biology. An RNA molecule is made of different types of secondary structure elements and an important RNA element named pseudoknot plays a key role in stabilizing the functional form of the molecule. However, due to the computational complexities associated with characterizing pseudoknotted RNA structures, most of the existing RNA sequence designer algorithms generally ignore this important structural element and therefore limit their applications. In this paper we present a new algorithm to design RNA sequences for pseudoknotted secondary structures. We use NUPACK as the folding algorithm to compute the equilibrium characteristics of the pseudoknotted RNAs, and describe a new adaptive defect weighted sampling algorithm named Enzymer to design low ensemble defect RNA sequences for targeted secondary structures including pseudoknots. We used a biological data set of 201 pseudoknotted structures from the Pseudobase library to benchmark the performance of our algorithm. We compared the quality characteristics of the RNA sequences we designed by Enzymer with the results obtained from the state of the art MODENA and antaRNA. Our results show our method succeeds more frequently than MODENA and antaRNA do, and generates sequences that have lower ensemble defect, lower probability defect and higher thermostability. Finally by using Enzymer and by constraining the design to a naturally occurring and highly conserved Hammerhead motif, we designed 8 sequences for a pseudoknotted cis-acting Hammerhead ribozyme. Enzymer is available for download at https://bitbucket.org/casraz/enzymer.

Divisions:Concordia University > Gina Cody School of Engineering and Computer Science > Computer Science and Software Engineering
Item Type:Article
Authors:Zandi, Kasra and Butler, Greg and Kharma, Nawwaf
Journal or Publication:Frontiers in Genetics
  • Concordia Open Access Author Fund
Digital Object Identifier (DOI):10.3389/fgene.2016.00129
Keywords:RNA secondary structure, sequence design algorithm, pseudoknot, hammerhead ribozyme, Pseudobase
ID Code:982265
Deposited On:21 Mar 2017 17:28
Last Modified:18 Jan 2018 17:54
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