  The folding of naturally occurring, single domain proteins is usually
well-described as a simple, single exponential process lacking significant
trapped states. Here we further explore the hypothesis that the smooth energy
landscape this implies, and the rapid kinetics it engenders, arises due to the
extraordinary thermodynamic cooperativity of protein folding. Studying
Miyazawa-Jernigan lattice polymers we find that, even under conditions where
the folding energy landscape is relatively optimized (designed sequences
folding at their temperature of maximum folding rate), the folding of
protein-like heteropolymers is accelerated when their thermodynamic
cooperativity enhanced by enhancing the non-additivity of their energy
potentials. At lower temperatures, where kinetic traps presumably play a more
significant role in defining folding rates, we observe still greater
cooperativity-induced acceleration. Consistent with these observations, we find
that the folding kinetics of our computational models more closely approximate
single-exponential behavior as their cooperativity approaches optimal levels.
These observations suggest that the rapid folding of naturally occurring
proteins is, at least in part, consequences of their remarkably cooperative
folding.
