title: Molecular dynamics investigations of hammerhead ribozyme RNA.
abstract: The hammerhead ribozyme, a small catalytic RNA molecule, cleaves, in the presence of magnesium ions, a specific phosphodiester bond within its own backbone, leading to 23-cyclic phosphate and 5-OH extremities. In order to study the dynamical flexibility of the hammerhead RNA, we performed molecular dynamics simulations of the solvated crystal structure of an active hammerhead ribozyme, obtained after flash-freezing crystals soaked with magnesium. Because of a careful equilibration protocol and the use of the Ewald summation in calculating the electrostatic interactions, the RNA structure remained close to the crystal structure, as attested by a root-mean-square deviation below 2.5 A after 750 ps of simulation. All Watson-Crick base pairs were intact at the end of the simulations. The tertiary interactions, such as the sheared G.A pairs and the U-turn, important for the stabilisation of the three-dimensional RNA fold, were also retained. The results demonstrate that molecular dynamics simulations can be successfully used to investigate the dynamical behaviour of a ribozyme, thus, opening a road to study the role of transient structural changes involved in ribozyme catalysis.
authors.affiliation: Institut de Biologie Moléculaire et Cellulaire du CNRS, Strasbourg, France.
authors.forename: T
authors.initials: T
authors.lastname: Hermann
authors.forename: P
authors.initials: P
authors.lastname: Auffinger
authors.forename: E
authors.initials: E
authors.lastname: Westhof
mesh_terms: D020029:Base Pairing; D001483:Base Sequence; D002384:Catalysis; D002413:Cations, Divalent; D003198:Computer Simulation; D008274:Magnesium / Q000737:chemistry; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D016337:RNA, Catalytic / Q000737:chemistry* / Q000378:metabolism; D012997:Solvents; D013816:Thermodynamics
chemical_list: D002413:Cations, Divalent; D016337:RNA, Catalytic; D012997:Solvents; D008274:Magnesium