Double-stranded helices are among the most significant components of DNA and RNA, and they display a surprising amount of structural diversity. For example, tandem repeating units of A-tracts and G-tracts in dsDNA show structural variations which enhance the vital coding functions of these molecules. These variations likely serve as signaling units for protein binding partners. Therefore, elucidating the mechanisms and factors that modulate these variations is of fundamental importance. While the structural diversity of dsDNA has been extensively studied, similar studies have not yet been performed for dsRNA. Because of the increasing awareness of RNA's diverse biological roles, such studies are timely and increasingly important. Progress towards the challenging goal of accurately modeling RNA duplexes and their variations requires tight integration of extensive experimental data with accurate theoretical studies. Here, to elucidate the structural variations in DNA and RNA duplexes we integrate solution x-ray scattering at wide-angles (WAXS) with all-atom molecular dynamics simulations. We successfully explore the conformational ensemble of duplex topologies for different sequences and salt conditions, identifying robust correlations between features in the WAXS profiles and duplex geometry. The synergy of these methods enables atomic-level insights, and reveals a marked contrast in the structural diversity of DNA and RNA duplexes. We find that dsRNA displays a marked sensitivity to the valence and identity of its associated cations. MD simulations of these ion distributions help to identify the factors that modulate the structural response of the duplexes. This study connects all-atom theoretical models of short DNA and RNA duplexes to measurement, and offers a robust method that can be readily expanded to study more general nucleic acid structures, dynamics, and energetics.

The structural plasticity of double stranded nucleic acids revealed by simulations and wide angle x-ray scattering (WAXS)

ACS Spring Meeting 2021

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