Molecular Dynamics Study of Twister Ribozyme: Role of Mg2+ Ions and the Hydrogen-Bonding Network in the Active Site

The recently discovered twister ribozyme is thought to utilize general acid–base catalysis in its self-cleavage mechanism, but the roles of nucleobases and metal ions in the mechanism are unclear. Herein, molecular dynamics simulations of the env22 twister ribozyme are performed to elucidate the structural and equilibrium dynamical properties, as well as to examine the role of Mg2+ ions and possible candidates for the general base and acid in the self-cleavage mechanism. The active site region and the ends of the pseudoknots were found to be less mobile than other regions of the ribozyme, most likely providing structural stability and possibly facilitating catalysis. A purported catalytic Mg2+ ion and the closest neighboring Mg2+ ion remained chelated and relatively immobile throughout the microsecond trajectories, although removal of these Mg2+ ions did not lead to any significant changes in the structure or equilibrium motions of the ribozyme on the microsecond time scale. In addition, a third metal ion...