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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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