The crystal structure of the precleaved form of the hepatitis delta virus (HDV) ribozyme reveals two G center dot U wobbles near the active site: a rare reverse G center dot U wobble involving a syn G base, and a standard G center dot U wobble at the cleavage site. The catalytic mechanism for this ribozyme has been proposed to involve a Mg(2+) ion bound to the reverse G center dot U wobble, as well as a protonated C75 base. We carried out molecular dynamics simulations to analyze metal ion interaction with the reverse and standard G center dot U wobbles and to investigate the impact of C75 protonation on the structure and motions of the ribozyme. We identified two types of Mg(2+) ions associated with the ribozyme, chelated and diffuse, at the reverse and standard G center dot U wobbles, respectively, which appear to contribute to catalysis and stability, respectively. These two metal ion sites exhibit relatively independent behavior. Protonation of C75 was observed to locally organize the active site in a manner that facilitates the catalytic mechanism, in which C75(+) acts as a general add and Mg(2+) as a Lewis acid. The simulations also indicated that the overall structure and thermal motions of the ribozyme are not significantly influenced by the catalytic Mg(2+) interaction or C75 protonation. This analysis suggests that the reaction pathway of the ribozyme is dominated by small local motions at the active site rather than large-scale global conformational changes. These results are consistent with a wealth of experimental data.