title: Small Details Matter: The 2'-Hydroxyl as a Conformational Switch in RNA.
abstract: While DNA is mostly a primary carrier of genetic information and displays a regular duplex structure, RNA can form very complicated and conserved 3D structures displaying a large variety of functions, such as being an intermediary carrier of the genetic information, translating such information into the protein machinery of the cell, or even acting as a chemical catalyst. At the base of such functional diversity is the subtle balance between different backbone, nucleobase, and ribose conformations, finely regulated by the combination of hydrogen bonds and stacking interactions. Although an apparently simple chemical modification, the presence of the 2'OH in RNA has a profound effect in the ribonucleotide conformational balance, adding an extra layer of complexity to the interactions network in RNA. In the present work, we have combined database analysis with extensive molecular dynamics, quantum mechanics, and hybrid QM/MM simulations to provide direct evidence on the dramatic impact of the 2'OH conformation on sugar puckering. Calculations provide evidence that proteins can modulate the 2'OH conformation to drive sugar repuckering, leading then to the formation of bioactive conformations. In summary, the 2'OH group seems to be a primary molecular switch contributing to specific protein-RNA recognition.
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology , 08028 Barcelona, Spain.|Joint BSC-IRB Program in Computational Biology, Institute for Research in Biomedicine , 08028 Barcelona, Spain.
authors.forename: Leonardo
authors.identifier: 0000-0001-5280-8579
authors.initials: L
authors.lastname: Darré
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology , 08028 Barcelona, Spain.|Joint BSC-IRB Program in Computational Biology, Institute for Research in Biomedicine , 08028 Barcelona, Spain.
authors.forename: Ivan
authors.initials: I
authors.lastname: Ivani
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology , 08028 Barcelona, Spain.|Joint BSC-IRB Program in Computational Biology, Institute for Research in Biomedicine , 08028 Barcelona, Spain.
authors.forename: Pablo D
authors.identifier: 0000-0002-5927-372X
authors.initials: PD
authors.lastname: Dans
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology , 08028 Barcelona, Spain.|Joint BSC-IRB Program in Computational Biology, Institute for Research in Biomedicine , 08028 Barcelona, Spain.
authors.forename: Hansel
authors.initials: H
authors.lastname: Gómez
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology , 08028 Barcelona, Spain.|Joint BSC-IRB Program in Computational Biology, Institute for Research in Biomedicine , 08028 Barcelona, Spain.
authors.forename: Adam
authors.initials: A
authors.lastname: Hospital
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology , 08028 Barcelona, Spain.|Joint BSC-IRB Program in Computational Biology, Institute for Research in Biomedicine , 08028 Barcelona, Spain.|Department of Biochemistry and Biomedicine, Faculty of Biology, University of Barcelona , 08028 Barcelona, Spain.
authors.forename: Modesto
authors.initials: M
authors.lastname: Orozco
mesh_terms: D006878:Hydroxides / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D011789:Quantum Theory; D012313:RNA / Q000737:chemistry*; D012399:Rotation
chemical_list: D006878:Hydroxides; D012313:RNA; C031356:hydroxide ion