Conformational analysis of nucleic acids for optimizing DNA and RNA topological models.

Conformational and configurational states of the sugar-phosphate backbone play an important role in DNA transcriptional and RNA translational events. In particular, the geometric parameters of the sugar ring dictate the degree of pucker, influencing the overall conformational state of the nucleic acid structure and its potential for base pairing and stacking. In this work, we explore nearly 50 years of nucleic acid structural data and compare over 4 million backbone torsion profiles of experimentally derived nucleic acid structures, and present a set of refined geometric parameters for nucleotides in common helix structures (A-, B-, and Z-helix). A comparison between X-ray and NMR structures for A- and B-helices underscores modelling challenges in accurately representing their conformational space. Furthermore, given the current interest in expanding the nucleoside library to include synthetic derivatives, these refined geometric parameters can serve in the development of conformational descriptors for analysing nucleic acid-based systems (e.g. small interfering RNA, microRNA, aptamers) with canonical and non-canonical base pairings.