%0 Journal Article
%T Molecular dynamics and mutational analysis of the catalytic and translocation cycle of RNA polymerase
%A Maria L Kireeva
%A Kristopher Opron
%A Steve A Seibold
%A C¨¦line Domecq
%A Robert I Cukier
%A Benoit Coulombe
%A Mikhail Kashlev
%A Zachary F Burton
%J BMC Biophysics
%D 2012
%I BioMed Central
%R 10.1186/2046-1682-5-11
%X All atom molecular dynamics simulations of Thermus thermophilus (Tt) RNAP reveal flexible hinges, located within the two helices at the base of the trigger loop, and two glycine hinges clustered near the N-terminal end of the bridge helix. As simulation progresses, these hinges adopt distinct conformations in the closed and open trigger loop structures. A number of residues (described as ¡°switch¡± residues) trade atomic contacts (ion pairs or hydrogen bonds) in response to changes in hinge orientation. In vivo phenotypes and in vitro activities rendered by mutations in the hinge and switch residues in Saccharomyces cerevisiae (Sc) RNAP II support the importance of conformational changes predicted from simulations in catalysis and translocation. During simulation, the elongation complex with an open trigger loop spontaneously translocates forward relative to the elongation complex with a closed trigger loop.Switching between catalytic and translocating RNAP forms involves closing and opening of the trigger loop and long-range conformational changes in the atomic contacts of amino acid side chains, some located at a considerable distance from the trigger loop and active site. Trigger loop closing appears to support chemistry and the fidelity of RNA synthesis. Trigger loop opening and limited bridge helix bending appears to promote forward nucleic acid translocation.
%U http://www.biomedcentral.com/2046-1682/5/11/abstract