Publication details

Understanding the Sequence Preference of Recurrent RNA Building Blocks using Quantum Chemistry: The Intrastrand RNA Dinucleotide Platform

Authors

MLÁDEK Arnošt ŠPONEROVÁ Judit KULHÁNEK Petr LU Xiang-Jun OLSON Wilma K. ŠPONER Jiří

Year of publication 2012
Type Article in Periodical
Magazine / Source Journal of Chemical Theory and Computation
MU Faculty or unit

Central European Institute of Technology

Citation
Web http://pubs.acs.org/doi/abs/10.1021/ct200712b
Doi http://dx.doi.org/10.1021/ct200712b
Field Biophysics
Keywords WATSON-CRICK/SUGAR-EDGE; MOLECULAR-DYNAMICS SIMULATIONS; BASE-PHOSPHATE INTERACTIONS; DENSITY-FUNCTIONAL THEORY; NUCLEIC-ACID STRUCTURES; BASIS-SET CONVERGENCE; AB-INITIO; FORCE-FIELD; TERTIARY INTERACTIONS; CHEMICAL CALCULATIONS
Description Folded RNA molecules are shaped by an astonishing variety of highly conserved non-canonical molecular interactions and backbone topologies. The dinucleotide platform is a widespread recurrent RNA modular building submotif formed by the side-by-side pairing of bases from two consecutive nucleotides within a single strand, with highly specific sequence preferences. This unique arrangement of bases is cemented by an intricate network of noncanonical hydrogen bonds and facilitated by a distinctive backbone topology. The present study investigates the gas-phase intrinsic stabilities of the three most common RNA dinucleotide platforms, 5'-GpU-3', ApA, and UpC, via state-of-the-art quantum-chemical (QM) techniques. The mean stability of base-base interactions decreases with sequence in the order GpU > ApA > UpC. Bader’s atoms-in-molecules analysis reveals that the N2(G)...O4(U) hydrogen bond of the GpU platform is stronger than the corresponding hydrogen bonds in the other two platforms. The mixed-pucker sugar-phosphate backbone conformation found in most GpU platforms, in which the 5'-ribose sugar (G) is in the C2'-endo form and the 3'-sugar (U) in the C3'-endo form, is intrinsically more stable than the standard A-RNA backbone arrangement, partially as a result of a favorable O2'...O2P intra-platform interaction. Our results thus validate the hypothesis of Lu et al. (Lu Xiang-Jun, et al. Nucleic Acids Res. 2010, 38, 4868-4876), that the superior stability of GpU platforms is partially mediated by the strong O2'...O2P hydrogen bond. In contrast, ApA and especially UpC platform-compatible backbone conformations are rather diverse and do not display any characteristic structural features. The average stabilities of ApA and UpC derived backbone conformers are also lower than those of GpU platforms. Our work also gives methodological insights into QM calculations of experimental RNA backbone geometries.
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