Stepping through an RNA structure: A novel approach to conformational analysis

Abstract

Drawing from the growing database of complex three-dimensional RNA structures, a systematic method has been developed for classifying and analyzing the variety of conformations adopted by nucleic acids. This method is based on the development of a reduced representation for nucleic acid backbone conformation, simplifying the formidable eight-dimensional problem that has long complicated nucleic acid conformational analysis. Two pseudotorsion angles (η and θ) have been defined, based on the selection of two appropriate pivot points along the RNA backbone, P and C4'. These pseudotorsions, together with a complete library of conventional torsion angles, can be calculated for any RNA structure or all-atom model using a new program called AMIGOS. Having computed η and θ pseudotorsions for each position on an RNA molecule, they can be represented on a two-dimensional plot similar to the φ-φ plots that have traditionally been used for protein conformational analysis. Like a Ramachandran plot, clusters of residues appear at discrete regions on an η-θ plot. Nucleotides within these clusters share conformational properties, often belonging to the same type of structural motif such as A-platforms, sheared tandem purine-purine pairs and GNRA tetraloops. An η-θ plot provides a two-dimensional representation of the conformational properties of an entire RNA molecule, facilitating rapid analysis of structural features. In addition to the utility of η-θ plots for intuitive visualization of conformational space, the pseudotorsional convention described here should significantly simplify approaches to macromolecular modeling of RNA structure.