(A) Hammerhead ribozyme conformation arising from hybridization between hammerhead ribozyme GUC19 and the target (BCRP) mRNA. The GUC triplet in the target site and the conserved nucleotides in the ribozyme catalytic core are in boldface. The site of cleavage, i.e., 3' of the C of the GUC triplet, is indicated by an arrow. (B) Thermodynamic cycle of free energy exchanges. ΔGdisruption is the target disruption energy, which represents the free energy cost to alter the local secondary structure at the target site for ribozyme binding; ΔGswitch is the change in free energy from a predicted ribozyme conformation to the "active" binding conformation in which the catalytic core is correctly folded and both binding arms are single-stranded; ΔGhybrid is the free energy gain from the ribozyme-target hybridization (see Methods for description of calculations).