Molten globule protein is not stablised by hydrogen bond why
Answers
New experimental results show that either gain or loss of close packing can be observed as a discrete step in protein folding or unfolding reactions. This finding poses a significant challenge to the conventional two-state model of protein folding. Results of interest involve dry molten globule intermediates, an expanded form of the protein that lacks appreciable solvent. When an unfolding protein expands to the dry molten globule state, side chains unlock and gain conformational entropy, while liquid-like van der Waals interactions persist. Four unrelated proteins are now known to form dry molten globules as the first step of unfolding, suggesting that such an intermediate may well be commonplace in both folding and unfolding. Data from the literature show that peptide amide protons are protected in the dry molten globule, indicating that backbone structure is intact despite loss of side chain close packing. Other complementary evidence shows that secondary structure formation provides a major source of compaction during folding. In our model, the major free-energy barrier separating unfolded from native states usually occurs during the transition between the unfolded state and the dry molten globule. The absence of close packing at this barrier provides an explanation for why ϕ-values, derived from a Brønsted-Leffler plot, depend primarily on structure at the mutational site and not on specific side chain interactions. The conventional two-state folding model breaks down when there are dry molten globule intermediates, a realization that has major implications for future experimental work on the mechanism of protein folding.