Abstract
Reaction mechanisms of ribozymes (“RNA enzymes”) revealed by the first-principles molecular dynamics simulations are discussed. The calculations are performed on an RNA fragment as a model structure of the catalytic site of ribozymes, in the absence/presence of explicit solvent water molecules, leading us to understanding the detailed mechanisms and the catalytic roles of divalent cations and solvent in in vitro reaction. Two cations, which are bound to the O2’/O5’ atoms of the catalytic nucleotide, and a hydroxide ion involved in a solvation shell of the cation bonding to the O2’ atom are indicated to concertedly decrease the activation barrier. The entire structure of a ribozyme molecule is now being investigated by using QM/MM hybrid molecular dynamics simulation. The computational methodology mentioned here is applicable also to other biological macromolecular systems.
