RNA Backbone Rotamers and Chiropraxis

RNA backbone is biologically important with many roles in reactions and interactions, but has historically been a challenge in structural determination. It has many atoms and torsions to place, and often there is less data on it than one might wish. This problem leads to both random and systematic error, producing noise in an already high-dimensional and complex distribution to further complicate data-driven analysis. With the advent of the ribosomal subunit structures published in 2000, large RNA structures at good resolution, it became possible to apply the Richardson laboratory's quality-filtering, visualization, and analysis techniques to RNA and develop new tools for RNA as well. A first set of 42 RNA backbone rotamers was identified, developed, and published in 2003; it has since been thoroughly overhauled in conjunction with the backbone group of the RNA Ontology Consortium to combine the strengths of different approaches, incorporate new data, and produce a consensus set of 46 conformers. Meanwhile, extensive work has taken place on developing validation and remodeling tools to correct and improve existing structures as well as to assist in initial fitting. The use of base-phosphate perpendicular distances to identify sugar pucker has proven very useful in both hand-refitting and the semi-automated process of using RNABC (RNA Backbone Correction), a program developed in conjunction with Dr. Jack Snoeyink's laboratory. The guanine riboswitch structure ur0039/1U8D, by Dr. Rob Batey's laboratory, has been collaboratively refit and rerefined as a successful test case of the utility of these tools and techniques. Their testing and development will continue, and they are expected to help to improve RNA structure determination in both ease and quality.