The term molten globule (MG) was first coined by A. Wada and M Ohgushi in 1983. It was first found in cytochrome c, which conserves a native-like secondary structure content but without the tightly packed protein interior, under low pH and high salt concentration. For cytochrome c and some other proteins, it has been shown that the molten globule state is a "thermodynamic state" clearly different both from the native and the denatured state, demonstrating for the first time the existence of a third equilibirum (i.e., intermediate) state.
The term "molten globule" is presently extended to include various types of partially folded protein states found in mildly denaturing conditions such as low pH (generally pH = 2), mild denaturant, or high temperature. Molten globules are collapsed and generally have some native-like secondary structure but a dynamic tertiary structure as seen by far and near circular dichroism (CD) spectroscopy, respectively. These traits are similar to those observed in the transient intermediate states found during the folding of certain proteins, especially globular proteins that undergo hydrophobic collapse, and therefore the term "molten globule" is also used to refer to certain protein folding intermediates corresponding to the narrowing region of the folding funnel higher in energy than the native state but lower than the denatured state. The molten globule ensembles sampled during protein folding and unfolding are thought to be roughly similar.
The MG structure is believed to lack the close packing of amino acid side chains that characterize the native state (N) of a protein. The transition from a denatured (U) state to a molten globule may be a two state process
- U ↔ MG
Or it may be a continuous transition, with no cooperativity and no apparent "switch" from one form to the other. The folding of some proteins can be modeled as a three-state kinetic process:
- U ↔ MG ↔ N
One of the difficulties in de novo protein design is achieving the side chain packing needed to create a stable native state rather than an ensemble of molten globules. Given a desired backbone conformation, side chain packing can be designed using variations of the dead-end elimination algorithm; however, attempts to design proteins of novel folds have difficulty using this method due to an absence of plausible backbone models.
Famous quotes containing the words globule and/or molten:
“The world is nothing, the man is all; in yourself is the law of all nature, and you know not yet how a globule of sap ascends; in yourself slumbers the whole of Reason; it is for you to know all, it is for you to dare all.”
—Ralph Waldo Emerson (18031882)
“Do you know the balancings of the clouds, the wondrous works of the one whose knowledge is perfect, you whose garments are hot when the earth is still because of the south wind? Can you, like him, spread out the skies, hard as a molten mirror?”
—Bible: Hebrew, Job 37:16-18.
One of Jobs comforters, of God.