Coupling of fast and slow modes in the reaction pathway of the minimal hammerhead ribozyme cleavage.

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 (Mg(2+)) 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.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Radhakrishnan R

doi

10.1529/biophysj.107.104661

subject

Has Abstract

pub_date

2007-10-01 00:00:00

pages

2391-9

issue

7

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(07)71494-7

journal_volume

93

pub_type

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