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Free energy barrier estimation of unfolding the α‐helical surfactant‐associated polypeptide C
Author(s) -
Zangi Ronen,
Kovacs Helena,
van Gunsteren Wilfred F.,
Johansson Jan,
Mark Alan E.
Publication year - 2001
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.1052
Subject(s) - metastability , pulmonary surfactant , chemistry , crystallography , thermodynamics , molecular dynamics , mole , activation barrier , molecule , computational chemistry , organic chemistry , physics
Molecular dynamics simulations were conducted to estimate the free energy barrier of unfolding surfactant‐associated polypeptide C (SP‐C) from an α‐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 CHCl 3 /CH 3 OH/0.1 M HCl at 32:64:5 (v/v/v), in which it undergoes an irreversible transformation to an insoluble aggregate that contains β‐sheet. On the basis of experimental observations, the free energy barrier was estimated to be ∼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 ∼20 kJ/mole. The results suggest a need to reconsider the applicability of a single‐mode activated process theory to protein unfolding. Proteins 2001;43:395–402. © 2001 Wiley‐Liss, Inc.