The nuclear magnetic resonance of CCCC RNA reveals a right-handed helix, and revised parameters for AMBER force field torsions improve structural predictions from molecular dynamics

Biochemistry. 2013 Feb 12;52(6):996-1010. doi: 10.1021/bi3010347. Epub 2013 Jan 29.

Abstract

The sequence dependence of RNA energetics is important for predicting RNA structure. Hairpins with C(n) loops are consistently less stable than hairpins with other loops, which suggests the structure of C(n) regions could be unusual in the "unfolded" state. For example, previous nuclear magnetic resonance (NMR) evidence suggested that polycytidylic acid forms a left-handed helix. In this study, UV melting experiments show that the hairpin formed by r(5'GGACCCCCGUCC) is less stable than r(5'GGACUUUUGUCC). NMR spectra for single-stranded C(4) oligonucleotide, mimicking the unfolded hairpin loop, are consistent with a right-handed A-form-like helix. Comparisons between NMR spectra and molecular dynamics (MD) simulations suggest that recent reparametrizations, parm99χ_YIL and parm99TOR, of the AMBER parm99 force field improve the agreement between structural features for C(4) determined by NMR and predicted by MD. Evidently, the force field revisions to parm99 improve the modeling of RNA energetics and therefore structure.

MeSH terms

  • Magnetic Resonance Spectroscopy
  • Models, Chemical
  • Molecular Dynamics Simulation*
  • Nucleic Acid Conformation
  • RNA / chemistry*
  • RNA / genetics
  • Thermodynamics

Substances

  • RNA