title: Structural stability, acidity, and halide selectivity of the fluoride riboswitch recognition site.
abstract: Using static and dynamics DFT methods we show that the Mg(2+)/F(-)/phosphate/water cluster at the center of the fluoride riboswitch is stable by its own and, once assembled, does not rely on any additional factor from the overall RNA fold. Further, we predict that the pKa of the water molecule bridging two Mg cations is around 8.4. We also demonstrate that the halide selectivity of the fluoride riboswitch is determined by the stronger Mg-F bond, which is capable of keeping together the cluster. Replacing F(-) with Cl(-) results in a cluster that is unstable under dynamic conditions. Similar conclusions on the structure and energetics of the cluster in the binding pocket of fluoride-inhibited pyrophosphatase suggest that the peculiarity of fluoride is in its ability to establish much stronger metal-halide bonds.
authors.affiliation: KAUST Catalysis Research Center, Physical Sciences and Engineering Division, King Abdullah University of Science and Technology , Thuwal 23955-6900, Kingdom of Saudi Arabia.
authors.forename: Mohit
authors.initials: M
authors.lastname: Chawla
authors.forename: Raffaele
authors.initials: R
authors.lastname: Credendino
authors.forename: Albert
authors.initials: A
authors.lastname: Poater
authors.forename: Romina
authors.initials: R
authors.lastname: Oliva
authors.forename: Luigi
authors.initials: L
authors.lastname: Cavallo
mesh_terms: D005459:Fluorides / Q000737:chemistry*; D008274:Magnesium / Q000737:chemistry; D015394:Molecular Structure; D010710:Phosphates / Q000737:chemistry; D011789:Quantum Theory; D059370:RNA Folding; D058928:Riboswitch / Q000235:genetics*; D013379:Substrate Specificity; D014867:Water / Q000737:chemistry
chemical_list: D010710:Phosphates; D058928:Riboswitch; D014867:Water; D008274:Magnesium; D005459:Fluorides