title: An Adaptive Defect Weighted Sampling Algorithm to Design Pseudoknotted RNA Secondary Structures.
abstract: 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.
authors: Computer Science Department, Concordia University Montreal, QC, Canada.
authors: Kasra
authors: K
authors: Zandi
authors: Computer Science Department, Concordia UniversityMontreal, QC, Canada; Centre for Structural and Functional Genomics, Concordia UniversityMontreal, QC, Canada.
authors: Gregory
authors: G
authors: Butler
authors: Centre for Structural and Functional Genomics, Concordia UniversityMontreal, QC, Canada; Electrical and Computer Engineering Department, Concordia UniversityMontreal, QC, Canada.
authors: Nawwaf
authors: N
authors: Kharma
keywords: Pseudobase; RNA secondary structure; hammerhead ribozyme; pseudoknot; sequence design algorithm