To the top

Page Manager: Webmaster
Last update: 9/11/2012 3:13 PM

Tell a friend about this page
Print version

De novo tertiary structur… - University of Gothenburg, Sweden Till startsida
Sitemap
To content Read more about how we use cookies on gu.se

De novo tertiary structure prediction using RNA123-benchmarking and application to Macugen

Journal article
Authors Emma S. E. Eriksson
L. Joshi
Martin Billeter
Leif A Eriksson
Published in Journal of Molecular Modeling
Volume 20
Issue 8
Pages 18
ISSN 1610-2940
Publication year 2014
Published at Department of Chemistry and Molecular Biology
Pages 18
Language en
Links dx.doi.org/10.1007/s00894-014-2389-...
Keywords RNA, RNA123, Tertiary structure prediction, Macugen, RNA SECONDARY STRUCTURE, G-CENTER-DOT, DIPOLAR COUPLING DATA, GROUP-I-INTRON, RIBOSOMAL-SUBUNIT, ANGSTROM RESOLUTION, CRYSTAL-STRUCTURE, INTERNAL LOOP, FORCE-FIELD, SEQUENCE
Subject categories Biochemistry, Biophysics

Abstract

The present benchmarking study utilizes the RNA123 program for de novo prediction of tertiary structures of a set of 50 RNA molecules for which X-ray/NMR structures are available, based on the nucleic acid sequence only. All molecules contain a hairpin loop motif and a helical structure of canonical and non-canonical base pairs, interrupted by bulges and internal loops to various degrees. RNA molecules with double helices made up purely by canonical base pairing, and molecules containing symmetric internal loops of non-canonical base pairing are, overall, very well predicted. Structures containing bulges and asymmetric internal loops, and more complex structures containing multiple bulges and internal loops in the same molecule, result in larger deviations from their X-ray/NMR predicted structures due to higher degree of flexibility of the nucleotide bases in these regions. In a majority of the molecules included herein, the RNA123 program was, however, able to predict the tertiary structure with a heavy atom RMSD of less than 5 angstrom to the X-ray/NMR structure, and the models were in most cases structurally closer to the X-ray/NMR structures than models predicted by MC-Fold and MC-Sym. A set of RNA molecules containing pseudoknot tertiary structure motifs were included, but neither of the programs was able to predict the folding of the single-stranded stem onto the helix without additional structural input. The RNA123 program was then applied to predict the tertiary structure of the RNA segment of Macugen (R), the first RNA aptamer approved for clinical use, and for which no tertiary structure has yet been solved. Four possible tertiary structures were predicted for this 27-nucleic-acid-long RNA molecule, which will be used in constructing a full model of the PEGylated aptamer and its interaction with the vascular endothelial growth factor target.

Page Manager: Webmaster|Last update: 9/11/2012
Share:

The University of Gothenburg uses cookies to provide you with the best possible user experience. By continuing on this website, you approve of our use of cookies.  What are cookies?