Departmental Papers (BE)

Document Type

Journal Article

Date of this Version

October 2007


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.


Reprinted from Biophysical Journal, Volume 93, Issue 7, October 2007, pages 2391-2399.
Publisher URL:

Additional Files

104661SupplementaryInformation.doc (2408 kB)
Supplemental Documentation

104661movie_S1.avi (8512 kB)
Supplemental movie 1

104661movie_S1.avi (8512 kB)
Supplemental movie 2

104661movie_S3.avi (11896 kB)
Supplemental movie 3



Date Posted: 14 October 2008

This document has been peer reviewed.