Free energy barrier estimation of unfolding the alpha-helical surfactant-associated polypeptide C

Molecular dynamics simulations were conducted to estimate the free energy b arrier of unfolding surfactant-associated polypeptide C (SP-C) from an or-h elical conformation. Experimental studies indicate that while the helical f old of SP-C is thermodynamically stable in phospholipid micelles, it is met astable 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 a ggregate that contains beta -sheet. On the basis of experimental observatio ns, the free energy barrier was estimated to be similar to 100 kJ/mole by a pplying Eyring's transition state theory to the experimental rate of unfold ing [Protein Sci 1998;7:2533-2540]. These studies prompted us to carry out simulations to investigate the unwinding process of two helical turns encom passing 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 simila r to 20 kJ/mole. The results suggest a need to reconsider the applicability of a single-mode activated process theory to protein unfolding. Proteins 2 001; 43:395-402. (C) 2001 Wiley-Liss, Inc.