The crystal structure of the precleaved form of the hepatitis delta virus (HDV) ribozyme reveals two G•U wobbles near the active site: a rare reverse G•U wobble involving a syn G base, and a standard G•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•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•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•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 acid 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.