Molten globule

A molten globule (MG) is a stable, partially folded protein structure found in mildly denaturing conditions such as low pH (generally pH = 2), mild denaturant, or high temperature. They are characterized by 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 trainsient intermediate states found during the folding of certain proteins and therefore the molten globule is believed to be analogous to protein folding intermediates. The MG structure is believed to lack most of the well packed 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. In any event, a model that can be used in some proteins is a three step 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 a molten globules.

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Further information

Is the molten globule a third phase of proteins?

http://www.stanford.edu/group/pandegroup/papers/MGpnas.pdf