Characterization of the Structure and Dynamics of the HDV Ribozyme in Different Stages Along the Reaction Path

The structure and dynamics of the hepatitis delta virus ribozyme (HDVr) are studied using molecular dynamics simulations in several stages along its catalytic reaction path, including reactant, activated precursor, and transition-state mimic and product states, departing from an initial structure based on the C75U mutant crystal structure (PDB: 1VC7). Results of five 350 ns molecular dynamics simulations reveal a spontaneous rotation of U-1 that leads to an in-line conformation and supports the role of protonated C75 as the general acid in the transition state. Our results provide rationale for the interpretation of several important experimental results and make experimentally testable predictions regarding the roles of key active site residues that are not obvious from any available crystal structures.