Dispersion interactions between urea and nucleobases contribute to the destabilization of RNA by urea in aqueous solution.

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TitleDispersion interactions between urea and nucleobases contribute to the destabilization of RNA by urea in aqueous solution.
Publication TypeJournal Article
Year of Publication2015
AuthorsKasavajhala, K, Bikkina, S, Patil, I, Mackerell, AD, U Priyakumar, D
JournalJ Phys Chem B
Volume119
Issue9
Pagination3755-61
Date Published2015 Mar 05
ISSN1520-5207
KeywordsBase Pairing, Hydrogen Bonding, Models, Molecular, RNA, RNA Stability, Solutions, Urea, Water
Abstract

Urea has long been used to investigate protein folding and, more recently, RNA folding. Studies have proposed that urea denatures RNA by participating in stacking interactions and hydrogen bonds with nucleic acid bases. In this study, the ability of urea to form unconventional stacking interactions with RNA bases is investigated using ab initio calculations (RI-MP2 and CCSD(T) methods with the aug-cc-pVDZ basis set). A total of 29 stable nucleobase-urea stacked complexes are identified in which the intermolecular interaction energies (up to -14 kcal/mol) are dominated by dispersion effects. Natural bond orbital (NBO) and atoms in molecules (AIM) calculations further confirm strong interactions between urea and nucleobases. Calculations on model systems with multiple urea and water molecules interacting with a guanine base lead to a hypothesis that urea molecules along with water are able to form cage-like structures capable of trapping nucleic acid bases in extrahelical states by forming both hydrogen-bonded and dispersion interactions, thereby contributing to the unfolding of RNA in the presence of urea in aqueous solution.

DOI10.1021/jp512414f
Alternate JournalJ Phys Chem B
PubMed ID25668757
PubMed Central IDPMC4352126
Grant ListR01 GM051501 / GM / NIGMS NIH HHS / United States
R29 GM051501 / GM / NIGMS NIH HHS / United States
GM051501 / GM / NIGMS NIH HHS / United States