Molten Globule


Molten globules are compact, partially folded conformations of proteins that have near‐native compactness, substantial secondary structure, little detectable tertiary structure and increased solvent‐exposed hydrophobic surface area relative to the native state.

Keywords: partially folded intermediate; protein folding; protein conformation; protein structure

Figure 1.

(a) Model of a native protein and (b) a cartoon illustrating the corresponding molten globule.



Arai M and Kuwajima K (1996) Rapid formation of a molten globule intermediate in refolding of alpha‐lactalbumin. Folding and Design 1(4): 275–287.

Dolgikh DA, Gilmanshin RI, Brazhnikov EV et al. (1981) Alpha‐Lactalbumin: compact state with fluctuating tertiary structure? FEBS Letters 136(2): 311–315.

Fink AL, Oberg KA and Seshadri S (1997) Discrete intermediates vs. molten globule models of protein folding: characterization of partially‐folded intermediates of apomyoglobin. Folding and Design 3(1): 19–25.

Finkelstein AV and Shakhnovich EI (1989) Theory of cooperative transitions in protein molecules. II. Phase diagram for a protein molecule in solution. Biopolymers 28(10): 1681–1694.

Ohgushi M and Wada A (1983) ‘Molten‐globule state’: a compact form of globular proteins with mobile side‐chains. FEBS Letters 164(1): 21–24.

Oliveberg M and Fersht AR (1996) Thermodynamics of transient conformations in the folding pathway of barnase: reorganization of the folding intermediate at low pH. Biochemistry 35(8): 2738–2749.

Ptitsyn OB, Pain RH, Semisotnov GV, Zerovnik E and Razgulyaev OI (1990) Evidence for a molten globule state as a general intermediate in protein folding. FEBS Letters 262(1): 20–24.

Raschke TM and Marqusee S (1997) The kinetic folding intermediate of ribonuclease H resembles the acid molten globule and partially unfolded molecules detected under native conditions. Nature Structural Biology 4(4): 298–304.

Schulman BA, Redfield C, Peng ZY, Dobson CM and Kim PS (1995) Different subdomains are most protected from hydrogen exchange in the molten globule and native states of human alpha‐lactalbumin. Journal of Molecular Biology 253(5): 651–657.

Shi L, Palleros DR and Fink AL (1994) Protein conformational changes induced by 1,1′‐bis(4‐anilino‐5‐naphthalenesulfonic acid)‐preferential binding to the molten globule of DnaK. Biochemistry 33(24): 7536–7546.

Further Reading

Baldwin RL (1991) Molten globules: specific or non‐specific folding intermediates. Chemtracts – Biochemistry and Molecular Biology 2: 379–389.

Baldwin RL (1996) On‐pathway versus off‐pathway folding intermediates. Folding and Design 1(1): R1–8.

Dill KA and Chan HS (1997) From Levinthal to pathways to funnels. Nature Structural Biology 4(1): 10–19.

Dill KA and Shortle D (1991) Denatured states of proteins. Annual Reviews of Biochemistry 60: 795–825.

Fink AL (1995) Compact intermediate states in protein folding. Annual Reviews of Biophysics and Biomolecular Structure 24: 495–522.

Freire E (1995) Thermodynamics of partly folded intermediates in proteins. Annual Reviews of Biophysics and Biomolecular Structure 24: 141–165.

Kuwajima K (1989) The molten globule state as a clue for understanding the folding and cooperativity of globular‐protein structure. Proteins 6(2): 87–103.

Makhatadze GI and Privalov PL (1995) Energetics of protein structure. Advances in Protein Chemistry 47: 307–425.

Ptitsyn OB (1995) Molten globule and protein folding. Advances in Protein Chemistry 47: 83–229.

Ptitsyn OB (1987) Protein folding: hypothesis and experiment. Journal of Protein Chemistry 6: 273–293.

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How to Cite close
Fink, Anthony L(Apr 2001) Molten Globule. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0003007]