Structural and Dynamical Classification of RNA Single-Base Bulges for Nanostructure Design

A comprehensive examination of the bulge motif is presented for a set of twenty single-base bulge structures obtained from the Protein Data Bank. Examples of the bulge motif found in X-ray-crystal and NMR structures are analyzed using molecular dynamics simulations. Three classes of the single-base bulge motif are defined according to the bulge residue type, and its surrounding base-pairs. The first class contains bulges in a stacked conformation, while the other two classes have the bulge predominantly or exclusively in a looped-out conformation. In the first class the bulges participate in hydrogen bond interactions with one of the neighboring base-pairs. While this modifies the backbone of the structure, the overall backbone shape typically remains relatively constant due to the absence of distal bonding across the helix grooves. In contrast, most of the bulges in the looped-out conformations (second and third class) create a more flexible and a more distinctive kink or induced bending along the backbone. In the second class, the orientation of bulge bases depends on their type and surrounding sequences, whereas the third class contains only cytosine bulges that prefer to remain exclusively in the looped-out conformation. An ultimate goal of this study is to utilize the bulge classes and the structural characteristics of the bulges for the design of RNA-bulge-based nanotemplates.