Departmental Papers (BE)
Title
Coupling of Fast and Slow Modes in the Reaction Pathway of the Minimal Hammerhead Ribozyme Cleavage
Document Type
Journal Article
Date of this Version
October 2007
Abstract
By employing classical molecular dynamics, correlation analysis of coupling between slow and fast dynamical modes, and free energy (umbrella) sampling using classical as well as mixed quantum mechanics molecular mechanics force fields, we uncover a possible pathway for phosphoryl transfer in the self-cleaving reaction of the minimal hammerhead ribozyme. The significance of this pathway is that it initiates from the minimal hammerhead crystal structure and describes the reaction landscape as a conformational rearrangement followed by a covalent transformation. The delineated mechanism is catalyzed by two metal (Mg2+) ions, proceeds via an in-line-attack by CYT 17 O2′ on the scissile phosphorous (ADE 1.1 P), and is therefore consistent with the experimentally observed inversion configuration. According to the delineated mechanism, the coupling between slow modes involving the hammerhead backbone with fast modes in the cleavage site appears to be crucial for setting up the in-line nucleophilic attack.
Supplemental Documentation
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Supplemental movie 1
104661movie_S1.avi (8512 kB)
Supplemental movie 2
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Supplemental movie 3
Date Posted: 14 October 2008
This document has been peer reviewed.
Comments
Reprinted from Biophysical Journal, Volume 93, Issue 7, October 2007, pages 2391-2399.
Publisher URL: http://dx.doi.org/10.1529/biophysj.107.104661