The molten globule is an intermediate state in
protein folding. First suggested by scientists such as
Peter Kim at
M.I.T. and Oleg Ptytsin at the
NIH, the molten globule is one way of dealing with
Levinthal's Paradox. The idea is that starting from a fully unfolded state, the protein rapidly collapses into a more compact, globular structure. This is often referred to as
hydrophobic collapse, because all the oily parts of the protein (parts that "fear" water) come together in the initial phase. Now the protein is in the molten globule state. While the protein is compact, the insides are still dancing around and rearranging, looking for a stable arrangement. Because everything is already somewhat compact, it is easier for the protein to find its final form than if it was an extended chain flopping about.
Certain conditions such as low pH (highly acidic conditions) can keep proteins in this state indefinitely, allowing scientists to study them. Due to the fact that they are transient and unstructured, molten globules are difficult to study. It has been shown that the molten globule shows some structure as measured by circular dichroism, or CD, a technique that measures secondary structure. We also know that the molten globule state is about 50% greater in volume than the final folded state. This phenomenon is still the issue of much debate and investigation in the protein folding community.