Swellix: a computational tool to explore RNA conformational space

BMC Bioinformatics

Methodology Article

Nathan Sloat¹  Jui-Wen Liu¹  Susan J. Schroeder¹ 

[1]101 Stephenson Parkway, 73019, Norman, OK, USA

关键词: RNA structure prediction;    RNA ensembles;    Conformational space;    RNA motif search;   

DOI  :  10.1186/s12859-017-1910-7

 received in 2017-07-12, accepted in 2017-11-01,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundThe sequence of nucleotides in an RNA determines the possible base pairs for an RNA fold and thus also determines the overall shape and function of an RNA. The Swellix program presented here combines a helix abstraction with a combinatorial approach to the RNA folding problem in order to compute all possible non-pseudoknotted RNA structures for RNA sequences. The Swellix program builds on the Crumple program and can include experimental constraints on global RNA structures such as the minimum number and lengths of helices from crystallography, cryoelectron microscopy, or in vivo crosslinking and chemical probing methods.ResultsThe conceptual advance in Swellix is to count helices and generate all possible combinations of helices rather than counting and combining base pairs. Swellix bundles similar helices and includes improvements in memory use and efficient parallelization. Biological applications of Swellix are demonstrated by computing the reduction in conformational space and entropy due to naturally modified nucleotides in tRNA sequences and by motif searches in Human Endogenous Retroviral (HERV) RNA sequences. The Swellix motif search reveals occurrences of protein and drug binding motifs in the HERV RNA ensemble that do not occur in minimum free energy or centroid predicted structures.ConclusionsSwellix presents significant improvements over Crumple in terms of efficiency and memory use. The efficient parallelization of Swellix enables the computation of sequences as long as 418 nucleotides with sufficient experimental constraints. Thus, Swellix provides a practical alternative to free energy minimization tools when multiple structures, kinetically determined structures, or complex RNA-RNA and RNA-protein interactions are present in an RNA folding problem.

【 授权许可】

CC BY   
© The Author(s). 2017