Free energy barrier estimation of unfolding the alpha-helical surfactant-associated polypeptide C.
Molecular dynamics simulations were conducted to estimate the free energy barrier of unfolding surfactant-associated polypeptide C (SP-C) from an alpha-helical conformation. Experimental studies indicate that while the helical fold of SP-C is thermodynamically stable in phospholipid micelles, it is metastable in a mixed organic solvent of CHCl3/CH3OH/0.1 M HCl at 32:64:5 (v/v/v), in which it undergoes an irreversible transformation to an insoluble aggregate that contains beta-sheet. On the basis of experimental observations, the free energy barrier was estimated to be approximately 100 kJ/mole by applying Eyring's transition state theory to the experimental rate of unfolding [Protein Sci 1998;7:2533-2540]. These studies prompted us to carry out simulations to investigate the unwinding process of two helical turns encompassing residues 25-32 in water and in methanol. The results give an upper bound estimation for the free energy barrier of unfolding of SP-C of approximately 20 kJ/mole. The results suggest a need to reconsider the applicability of a single-mode activated process theory to protein unfolding.
Zangi
R
R
Groningen Biomolecular Sciences and Biotechnology Institute, Department of Biophysical Chemistry, University of Groningen, Groningen, The Netherlands.
Kovacs
H
H
van Gunsteren
W F
WF
Johansson
J
J
Mark
A E
AE
D000595:Amino Acid Sequence; D000818:Animals; D003198:Computer Simulation; D006801:Humans; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011510:Proteolipids / Q000737:chemistry*; D011663:Pulmonary Surfactants / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D013816:Thermodynamics
D010455:Peptides; D011510:Proteolipids; D011663:Pulmonary Surfactants; D012997:Solvents; C050632:polypeptide C