title: Molecular mechanism for preQ1-II riboswitch function revealed by molecular dynamics.
abstract: Riboswitches are RNA molecules that regulate gene expression using conformational change, affected by binding of small molecule ligands. A crystal structure of a ligand-bound class II preQ1 riboswitch has been determined in a previous structural study. To gain insight into the dynamics of this riboswitch in solution, eight total molecular dynamic simulations, four with and four without ligand, were performed using the Amber force field. In the presence of ligand, all four of the simulations demonstrated rearranged base pairs at the 3' end, consistent with expected base-pairing from comparative sequence analysis in a prior bioinformatic analysis; this suggests the pairing in this region was altered by crystallization. Additionally, in the absence of ligand, three of the simulations demonstrated similar changes in base-pairing at the ligand binding site. Significantly, although most of the riboswitch architecture remained intact in the respective trajectories, the P3 stem was destabilized in the ligand-free simulations in a way that exposed the Shine-Dalgarno sequence. This work illustrates how destabilization of two major groove base triples can influence a nearby H-type pseudoknot and provides a mechanism for control of gene expression by a fold that is frequently found in bacterial riboswitches.
authors.affiliation: Department of Biochemistry & Biophysics and Center for RNA Biology, University of Rochester Medical Center, Rochester, New York 14642, USA.
authors.forename: Asaminew H
authors.initials: AH
authors.lastname: Aytenfisu
authors.affiliation: Department of Biochemistry & Biophysics and Center for RNA Biology, University of Rochester Medical Center, Rochester, New York 14642, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Liberman
authors.affiliation: Department of Biochemistry & Biophysics and Center for RNA Biology, University of Rochester Medical Center, Rochester, New York 14642, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Wedekind
authors.affiliation: Department of Biochemistry & Biophysics and Center for RNA Biology, University of Rochester Medical Center, Rochester, New York 14642, USA Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, New York 14642, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Mathews
mesh_terms: D020029:Base Pairing / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D008024:Ligands; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D059370:RNA Folding / Q000235:genetics; D012329:RNA, Bacterial / Q000235:genetics; D058928:Riboswitch / Q000235:genetics*
chemical_list: D008024:Ligands; D012329:RNA, Bacterial; D058928:Riboswitch
keywords: RNA structure; amber; molecular dynamics; riboswitch