Does the molten globule have a native-like tertiary fold?

One of the mysteries in protein folding is how folding intermediates direct a protein to its unique final structure. To address this question, we have studied the molten globule formed by the α-helical domain of α-lactalbumin (α-LA) and demonstrated that it has a native-like tertiary fold, even in the absence of rigid, extensive side chain packing. These studies suggest that the role of molten globule intermediates in protein folding is to maintain an approximate native backbone topology while still allowing minor structural rearrangements to occur.