Origin of Mutational Effects at the C3 and G8 Positions on Hammerhead Ribozyme Catalysis from Molecular Dynamics Simulations

Journal of the American Chemical Society vol. 130  p. 7168-7169  DOI: 10.1021/ja711242b
PMID/PMCID: PMC2733889 Published: 2008-06-11 

Tai-Sung Lee [ ] , Darrin M. York [ ]

  View Full Article
 Download PDF


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.