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

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

Tai-Sung Lee, Darrin M. York
J. Am. Chem. Soc. (2008) 130, 7168-7169
DOI: 10.1021/ja711242b
PMCID: PMC2733889

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.


Keywords: RNA, hammerhead, ribozyme, catalysis, molecular dynamics
Research Areas: RNA Folding, Structure, and Catalysis

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