title: Origin of mutational effects at the C3 and G8 positions on hammerhead ribozyme catalysis from molecular dynamics simulations.
abstract: A series of ten 60 ns molecular dynamics (MD) simulations of the native and mutated full length hammerhead ribozymes in the reactant state and in an activated precursor state (G8:2'OH deprotonated) are reported. Mutant simulations include the C3U, G8A, and G8I single mutants and a C3U/G8A double mutant that exhibits an experimental rescue effect. The results provide critical details into the origin of the observed mutation effects and support a mechanism where the 2'OH of G8 acts as a general acid catalyst that is held in position through Watson-Crick hydrogen bonding between G8 and C3.
authors.affiliation: Consortium for Bioinformatics and Computational Biology, and Department of Chemistry, University of Minnesota, 207 Pleasant Street SE, Minneapolis, Minnesota 55455, USA.
authors.forename: Tai-Sung
authors.initials: TS
authors.lastname: Lee
authors.forename: Darrin M
authors.initials: DM
authors.lastname: York
mesh_terms: D001665:Binding Sites; D002384:Catalysis; D003198:Computer Simulation; D006860:Hydrogen Bonding; D007700:Kinetics; D008274:Magnesium / Q000737:chemistry / Q000378:metabolism; D009154:Mutation; D016337:RNA, Catalytic / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D055672:Static Electricity; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry
chemical_list: D016337:RNA, Catalytic; C427204:hammerhead ribozyme; D014867:Water; D008274:Magnesium