Proper folding of proteins is essential for their biological activity. In general, the functional conformation of a protein is the conformation with lowest energy. This means that if an unfolded protein is allowed to reach equilibrium, it should assemble automatically into its native, functioning folded state. Why then is there a need for molecular chaperones and chaperonins in cells?

In order to the protein fold into the tertiary and, by consequence, the operational structure, an energy barrier has to be broken. The lowest Gibbs energy is achieved when the protein is in the native state. But, by looking the a free energy diagram of a protein, the transformation of a misfolded to a native state has to be performed by a catalyzation process using chaperone or a chaperonin, depending of the organism.