Computational prediction of riboswitch tertiary structures including pseudoknots by RAGTOP: A hierarchical graph sampling approach

Namhee Kim, Mai Zahran, Tamar Schlick

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The modular organization of RNA structure has been exploited in various computational and theoretical approaches to identify RNA tertiary (3D) motifs and assemble RNA structures. Riboswitches exemplify this modularity in terms of both structural and functional adaptability of RNA components. Here, we extend our computational approach based on tree graph sampling to the prediction of riboswitch topologies by defining additional edges to mimick pseudoknots. Starting from a secondary (2D) structure, we construct an initial graph deduced from predicted junction topologies by our data-mining algorithm RNAJAG trained on known RNAs; we sample these graphs in 3D space guided by knowledge-based statistical potentials derived from bending and torsion measures of internal loops as well as radii of gyration for known RNAs. We present graph sampling results for 10 representative riboswitches, 6 of them with pseudoknots, and compare our predictions to solved structures based on global and local RMSD measures. Our results indicate that the helical arrangements in riboswitches can be approximated using our combination of modified 3D tree graph representations for pseudoknots, junction prediction, graph moves, and scoring functions. Future challenges in the field of riboswitch prediction and design are also discussed.

Original languageEnglish (US)
Title of host publicationMethods in Enzymology
PublisherAcademic Press Inc.
Pages115-135
Number of pages21
DOIs
StatePublished - 2015

Publication series

NameMethods in Enzymology
Volume553
ISSN (Print)0076-6879
ISSN (Electronic)1557-7988

Keywords

  • Hierarchical graph sampling
  • RAG
  • RAGTOP
  • RNAJAG
  • Riboswitch
  • Structure prediction

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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    Kim, N., Zahran, M., & Schlick, T. (2015). Computational prediction of riboswitch tertiary structures including pseudoknots by RAGTOP: A hierarchical graph sampling approach. In Methods in Enzymology (pp. 115-135). (Methods in Enzymology; Vol. 553). Academic Press Inc.. https://doi.org/10.1016/bs.mie.2014.10.054