Metalloprotein complexes that are able to explore a range of structures will isomerize as the temperature is raised when the isomeric state is coupled to a soft mode in the vibrational spectrum. A model based on a local mode description of the metal center provides insight into the driving forces for the isomerization reaction, which is the local analog of global melting transitions well-known for cooperative systems (proteins, nucleic acids, and crystals). Thermal isomerization of the active site in manganese superoxide dismutase appears to be an example of this type of transition, the azide complex converting between six- and five-coordinate forms at a temperature T-m = 220 K. In superoxide dismutase, mode melting defines the pathway for ligand binding at ambient temperatures, stabilizing the functional form of the active site. Thermal isomerization may be a very general characteristic of complex molecules in solution or in the gas phase, reflecting a transition in molecular dynamics.