Conformational deformability of RNA: a harmonic mode analysis

The harmonic mode analysis method was used to characterize the conformational deformability of regular Watson-Crick paired, mismatch- and bulge-containing RNA. Good agreement between atomic Debye-Waller factors derived from x-ray crystallography of a regular RNA oligonucleotide and calculated atomic fluctuations was obtained. Calculated helical coordinate fluctuations showed a small sequence dependence of up to approximately 30-50%. A negative correlation between motions at a given base pair step and neighboring steps was found for most helical coordinates. Only very few calculated modes contribute significantly to global motions such as bending, twisting, and stretching of the RNA molecules. With respect to a local helical description of the RNA helix our calculations suggest that RNA bending is mostly due to a periodic change in the base pair step descriptors slide and roll. The presence of single guanine:uridine or guanine:adenine mismatches had little influence on the calculated RNA flexibility. In contrast, for tandem guanine:adenine base pairs the harmonic mode approach predicts a significantly reduced conformational flexibility in the case of a sheared arrangement and slightly enhanced flexibility for a face-to-face (imino proton) pairing relative to regular RNA. The presence of a single extra adenine bulge nucleotide stacked between flanking sequences resulted in an increased local atomic mobility around the bulge site (approximately 40%) and a slightly enhanced global bending flexibility. For an adenine bulge nucleotide in a looped-out conformation a strongly enhanced bulge nucleotide mobility but no increased bending flexibility compared to regular RNA was found.