Noncanonical alpha/gamma Backbone Conformations in RNA and the Accuracy of Their Description by the AMBER Force Field

0476549 - BFÚ 2018 RIV US eng J - Journal Article
Zgarbová, M. - Jurečka, P. - Banáš, P. - Havrila, Marek - Šponer, Jiří - Otyepka, M.
Noncanonical alpha/gamma Backbone Conformations in RNA and the Accuracy of Their Description by the AMBER Force Field.
Journal of Physical Chemistry B. Roč. 121, č. 11 (2017), s. 2420-2433. ISSN 1520-6106. E-ISSN 1520-5207
Institutional support: RVO:68081707
Keywords : molecular-dynamics simulations * sugar-phosphate backbone * free-energy landscape * ribosomal-rna
OECD category: Physical chemistry
Impact factor: 3.146, year: 2017

The sugar-phosphate backbone of RNA can exist in diverse rotameric substates, giving RNA molecules enormous conformational variability. The most frequent noncanonical backbone conformation in RNA is alpha/gamma = t/t, which is derived from the canonical backbone by a crankshaft motion and largely preserves the standard geometry of the RNA duplex. A similar conformation also exists in DNA, where it has been extensively studied and shown to be involved in DNA-protein interactions. However, the function of the alpha/gamma = t/t conformation in RNA is poorly understood. Here, we present molecular dynamics simulations of several prototypical RNA structures obtained from X-ray and NMR experiments, including canonical and mismatched RNA duplexes, UUCG and GAGA tetraloops, Loop E, the sarcin ricin loop, a parallel guanine quadruplex, and a viral pseudoknot. The stability of various noncanonical alpha/gamma backbone conformations was analyzed with two AMBER force fields, ff99bscO chi(OL3) and ff99bscO chi(OL3) with the recent epsilon zeta(OL1) and beta(OL1) corrections for DNA. Although some alpha/gamma substates were stable with seemingly well-described equilibria, many were unstable in our simulations. Notably, the most frequent noncanonical conformer alpha/gamma = t/t was unstable in both tested force fields. Possible reasons for this instability are discussed. Our work reveals a potentially important artifact in RNA force fields and highlights a need for further force field refinement.
Permanent Link: http://hdl.handle.net/11104/0273031