title: Intrinsic contribution of the 2'-hydroxyl to RNA conformational heterogeneity.
abstract: Canonical duplex RNA assumes only the A-form conformation at the secondary structure level while, in contrast, a wide range of noncanonical, tertiary conformations of RNA occur. Here, we show how the 2'-hydroxyl controls RNA conformational properties. Quantum mechanical calculations reveal that the orientation of the 2'-hydroxyl significantly alters the intrinsic flexibility of the phosphodiester backbone, favoring the A-form in duplex RNA when it is in the base orientation and facilitating sampling of a wide range of noncanonical, tertiary structures when it is in the O3' orientation. Influencing the orientation of the 2'-hydroxyl are interactions with the environment, as evidenced by crystallographic survey data, indicating the 2'-hydroxyl to sample more of the O3' orientation in noncanonical RNA structures. These results indicate that the 2'-hydroxyl acts as a "switch", both limiting the conformation of RNA to the A-form at the secondary structure level and allowing RNA to sample a wide range of noncanonical tertiary conformations.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland 21201, USA.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Denning
authors.forename: Alexander D
authors.initials: AD
authors.lastname: MacKerell
mesh_terms: D004247:DNA / Q000737:chemistry; D006878:Hydroxides / Q000737:chemistry*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011789:Quantum Theory; D012313:RNA / Q000737:chemistry*
chemical_list: D006878:Hydroxides; D012313:RNA; D004247:DNA; C031356:hydroxide ion