lsosteric and Nonisosteric Base Pairs in RNA Motifs: Molecular Dynamics and Bioinformatics Study of the Sarcin Ricin Internal Loop

0422258 - BFÚ 2014 RIV US eng J - Journal Article
Havrila, Marek - Réblová, K. - Zirbel, C.L. - Leontis, N. B.
lsosteric and Nonisosteric Base Pairs in RNA Motifs: Molecular Dynamics and Bioinformatics Study of the Sarcin Ricin Internal Loop.
Journal of Physical Chemistry B. Roč. 117, č. 46 (2013), s. 14302-14319. ISSN 1520-6106. E-ISSN 1520-5207
R&D Projects: GA ČR GBP305/12/G034; GA MŠMT ED1.1.00/02.0068
Institutional research plan: CEZ:AV0Z50040702
Institutional support: RVO:68081707
Keywords : 23S RIBOSOMAL-RNA * PARTICLE MESH EWALD * NUCLEIC-ACIDS
Subject RIV: BO - Biophysics
Impact factor: 3.377, year: 2013

The sarcin-ricin RNA motif (SR motif) is one of the most prominent recurrent RNA building blocks that occurs in many different RNA contexts and folds autonomously, that is, in a context-independent manner. In this study, we combined bioinformatics analysis with explicit-solvent molecular dynamics (MD) simulations to better understand the relation between the RNA sequence and the evolutionary patterns of the SR motif. A SHAPE probing experiment was also performed to confirm the fidelity of the MD simulations. We identified 57 instances of the SR motif in a nonredundant subset of the RNA X-ray structure database and analyzed their base pairing, base phosphate, and backbone backbone interactions. We extracted sequences aligned to these instances from large rRNA alignments to determine the frequency of occurrence for different sequence variants. We then used a simple scoring scheme based on isostericity to suggest 10 sequence variants with a highly variable expected degree of compatibility with the SR motif 3D structure. We carried out MD simulations of SR motifs with these base substitutions.
Permanent Link: http://hdl.handle.net/11104/0228459