title: Noncanonical α/γ Backbone Conformations in RNA and the Accuracy of Their Description by the AMBER Force Field.
abstract: 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 α/γ = 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 α/γ = 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 α/γ backbone conformations was analyzed with two AMBER force fields, ff99bsc0χOL3and ff99bsc0χOL3with the recent εζOL1and βOL1corrections for DNA. Although some α/γ substates were stable with seemingly well-described equilibria, many were unstable in our simulations. Notably, the most frequent noncanonical conformer α/γ = 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.
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacky University , 17. listopadu 12, 77146 Olomouc, Czech Republic.
authors.forename: Marie
authors.initials: M
authors.lastname: Zgarbová
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacky University , 17. listopadu 12, 77146 Olomouc, Czech Republic.
authors.forename: Petr
authors.identifier: 0000-0002-3741-3672
authors.initials: P
authors.lastname: Jurečka
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacky University , 17. listopadu 12, 77146 Olomouc, Czech Republic.
authors.forename: Pavel
authors.initials: P
authors.lastname: Banáš
authors.affiliation: Institute of Biophysics, Academy of Sciences of the Czech Republic , Královopolská 135, 612 65 Brno, Czech Republic.
authors.forename: Marek
authors.initials: M
authors.lastname: Havrila
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacky University , 17. listopadu 12, 77146 Olomouc, Czech Republic.|Institute of Biophysics, Academy of Sciences of the Czech Republic , Královopolská 135, 612 65 Brno, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Šponer
authors.affiliation: Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacky University , 17. listopadu 12, 77146 Olomouc, Czech Republic.
authors.forename: Michal
authors.identifier: 0000-0002-1066-5677
authors.initials: M
authors.lastname: Otyepka
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry; D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry*; D020871:RNA Stability
chemical_list: D052157:Aptamers, Nucleotide; D012313:RNA