Effect of viscosity on the kinetics of alpha-helix and beta-hairpin formation

Nanosecond laser temperature jumps and fluorescence detection were used to measure the effect of viscosity on the kinetics of beta -helix and beta -ha irpin formation in peptides containing 21 and 16 amino acids. respectively. The solvent viscosity was changed by adding glucose and sucrose at concent rations that do not significantly alter the equilibrium unfolding curves. A nalysis of the temperature dependence at fixed solvent compositions shows t hat the activation energies are also unaffected, indicating that the slowin g of the relaxation rates upon addition of the sugars results entirely from their dynamical effect of increasing the solvent viscosity (eta). The rate of beta -hairpin formation was found to vary nearly as 1/eta, as predicted by Kramers theory in the high friction limit. In contrast, the rate of alp ha -helix formation exhibited a fractional viscosity dependence (k = eta (- alpha)) with an exponent alpha approximate to 0.6. The intrinsic activation energy for the elementary kinetic step of rotating a pair of backbone dihe dral angles, obtained using a simple statistical mechanical model, is near zero for the beta -hairpin but is similar to5 kcal/mol for the alpha -helix . If a higher barrier frequency can be associated with the larger activatio n energy, the fractional viscosity dependence for the alpha -helix may resu lt from the fact that motion across the barrier top is faster than the solv ent relaxation time.