Conformational deformability of RNA: A harmonic mode analysis

The harmonic mode analysis method was used to characterize the conformation al deformability of regular Watson-Crick paired, mismatch- and bulge-contai ning 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 show ed a small sequence dependence of up to similar to 30-50%. A negative corre lation between motions at a given base pair step and neighboring steps was found for most helical coordinates. Only very few calculated modes contribu te significantly to global motions such as bending, twisting, and stretchin g 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 peri odic change in the base pair step descriptors slide and roll. The presence of single guanine:uridine or guanine:adenine mismatches had little influenc e on the calculated RNA flexibility. In contrast, for tandem guanine:adenin e base pairs the harmonic mode approach predicts a significantly reduced co nformational 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 stacke d between flanking sequences resulted in an increased local atomic mobility around the bulge site (similar to 40%) and a slightly enhanced global bend ing flexibility. For an adenine bulge nucleotide in a looped-out conformati on a strongly enhanced bulge nucleotide mobility but no increased bending f lexibility compared to regular RNA was found.