Molecular dynamics suggest multifunctionality of an adenine imino group in acid-base catalysis of the hairpin ribozyme.

ABSTRACT: Despite numerous structural and biochemical investigations, the catalytic mechanism of hairpin ribozyme self-cleavage remains elusive. To gain insight into the coupling of active site dynamics with activity of this small catalytic RNA, we analyzed a total of approximately 300 ns of molecular dynamics (MD) simulations. Our simulations predict improved global stability for an in vitro selected "gain of function" mutation, which is validated by native gel electrophoretic mobility shift assay. We observe that active site nucleobases and water molecules stabilize a geometry favorable to catalysis through a dynamic hydrogen bonding network. Simulations in which A38 is unprotonated show its N1 move into close proximity of the active site 2'-OH, indicating that A38 may act as a general base during

SUBMITTER: Ditzler MA 

PROVIDER: S-EPMC2661834 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature